Methotrexate 7.5mg/0.15ml solution for injection pre-filled disposable devices
Prescription only
Requires a prescription from a doctor or prescriber
Drugs used in rheumatic diseases and gout
Active ingredients:
Methotrexate
No active safety alerts
Official documents, adverse reaction reporting, and safety monitoring
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Official medicine documents
Source: MHRA Products DatabaseOGL 3.0
Updated 3 months ago(16 Jan 2026)Safety monitoring data
Yellow Card reports
MHRA
The MHRA Yellow Card scheme collects reports of suspected side effects from healthcare professionals and patients. View the Drug Analysis Profile (iDAP) for real-world adverse reaction data.
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Suspected adverse reactions reported for Methotrexate
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Data from the MHRA Yellow Card scheme. A reported reaction does not necessarily mean the medicine caused it. Contains public sector information licensed under the Open Government Licence v3.0.
EudraVigilance
EMA
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Suspected adverse reactions reported for Methotrexate
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EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
5 branded products available
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Part of the Metoject brand family (generic: Methotrexate)
5 products
MHRA licensed products
View all licensed products for Methotrexate on the MHRA register
Methofill 7.5mg/0.15ml solution for injection pre-filled injector
Metoject PEN 7.5mg/0.15ml solution for injection pre-filled pens
Metoject PEN 7.5mg/0.15ml solution for injection pre-filled pens
Metoject PEN 7.5mg/0.15ml solution for injection pre-filled pens
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£12.87indicative price
This is the NHS Drug Tariff indicative price used for reimbursement purposes. It may not reflect the price paid by patients or pharmacies.
View full Drug TariffSource: NHS Drug Tariff via NHSBSA. Derived from dm+d VMPP (Virtual Medicinal Product Pack) pricing data. Contains public sector information licensed under the Open Government Licence v3.0.
WHO defined daily dose (DDD)
2.5 mg
Not a recommended dose. The DDD is the assumed average maintenance dose per day for a drug used for its main indication in adults. It is a statistical measure used for research and comparison purposes only.
Source: WHO Collaborating Centre for Drug Statistics Methodology, distributed via NHS dm+d BNF mapping files. Contains public sector information licensed under the Open Government Licence v3.0.
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Methotrexate 100mg/4ml solution for injection pre-filled syringes
Injection
100mg/4ml
Same therapeutic group
Similarity based on WHO Anatomical Therapeutic Chemical (ATC) classification and NHS BNF section grouping. Source data: NHS dm+d via TRUD (OGL v3.0), WHO ATC/DDD Index.
NHS prescribing volume and spending trends
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Clinical guidelines and formulary information
British National Formulary
Methotrexate
BNF
Drug monograph — bnf.nice.org.ukSource: British National Formulary, NICE. Joint Formulary Committee. Contains public sector information licensed under the Open Government Licence v3.0.
NICE clinical guidance(13)
Rheumatoid arthritis in adults: management (NG100)
NG100
NICE guideline
Updated Oct 2020Crohn's disease: management (NG129)
NG129
NICE guideline
Updated May 2019Psoriasis: assessment and management (CG153)
CG153
Clinical guideline
Updated Sept 2017Upadacitinib for treating severe rheumatoid arthritis (TA665)
TA665
Technology appraisal
Updated Dec 2020Certolizumab pegol for treating rheumatoid arthritis after inadequate response to a TNF-alpha inhibitor (TA415)
TA415
Technology appraisal
Updated Oct 2016Sarilumab for moderate to severe rheumatoid arthritis (TA485)
TA485
Technology appraisal
Updated Nov 2017Filgotinib for treating moderate to severe rheumatoid arthritis (TA676)
TA676
Technology appraisal
Updated Feb 2021Upadacitinib for treating moderate rheumatoid arthritis (TA744)
TA744
Technology appraisal
Updated Nov 2021Adalimumab, etanercept, infliximab, certolizumab pegol, golimumab, tocilizumab and abatacept for rheumatoid arthritis not previously treated with DMARDs or after conventional DMARDs only have failed (TA375)
TA375
Technology appraisal
Updated Jan 2016Tofacitinib for moderate to severe rheumatoid arthritis (TA480)
TA480
Technology appraisal
Updated Oct 2017Tocilizumab for the treatment of systemic juvenile idiopathic arthritis (TA238)
TA238
Technology appraisal
Updated Dec 2011Abatacept, adalimumab, etanercept and tocilizumab for treating juvenile idiopathic arthritis (TA373)
TA373
Technology appraisal
Updated Dec 2015Adalimumab, etanercept, infliximab and abatacept for treating moderate rheumatoid arthritis after conventional DMARDs have failed (TA715)
TA715
Technology appraisal
Updated Jul 2021Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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Search for this medicine at major UK pharmacy chains. These links open the retailer's own website — results depend on their current online catalogue.
Supply & product information
Official product databases and supply status monitoring
Pharmacy links redirect to the retailer's own search and do not represent real-time stock levels. emc (electronic medicines compendium) is operated by Datapharm Ltd. Shortage information sourced from NHS Specialist Pharmacy Service (SPS), sps.nhs.uk.
Codes for healthcare professionals and prescribing systems
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These codes are used by healthcare IT systems and prescribers to identify this medicine.
NHS UK identifiers
Browse tools
SNOMED CT and dm+d codes from NHS TRUD (Technology Reference data Update Distribution), licensed under the Open Government Licence v3.0. BNF codes from NHS Business Services Authority (NHSBSA). ATC codes from the WHO Collaborating Centre for Drug Statistics Methodology (whocc.no).
Active and completed clinical studies from ClinicalTrials.gov
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Searching UK clinical trials...
Source: ClinicalTrials.gov, a database of the U.S. National Library of Medicine (NLM), National Institutes of Health (NIH). Data accessed via ClinicalTrials.gov API v2. Trial information is provided for research purposes and does not constitute medical advice.
Pharmacology and chemical data from DrugBank
Key facts
Drug status
Approved
Major interactions
114 found
Half-life
3 to 10 hours
Mechanism
Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate.
Food interactions
5 warnings
Human targets
5 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
64-90%
Methotrexate has a bioavailability of 64-90%, though this decreases at oral doses above 25mg due to saturation of the carrier mediated transport of methotrexate..
[A180322]…
[A180322]…
Half-life
3 to 10 hours
The half life of low dose methotrexate is 3 to 10 hours in adults.
[L7144]…
[L7144]…
Protein binding
46.5-54%
Methotrexate is 46.5-54% bound to plasma proteins.
[A180322]
[A180322]
Volume of distribution
1L/kg
The volume of distribution of methotrexate at steady state is approximately 1L/kg.
[A180322]
[A180322]
Metabolism
Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues.
[A180322][L7180]…
[A180322][L7180]…
Elimination
80%
Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite.
[A180322]…
[A180322]…
Clearance
Methotrexate clearance varies widely between patients and decreases with increasing doses.
[A180400]…
[A180400]…
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Methotrexate is a folate derivative that inhibits several enzymes responsible for nucleotide synthesis.[A180322] This inhibition leads to suppression of inflammation as well as prevention of cell division.[A180322] Because of these effects, methotrexate is often used to treat inflammation caused by arthritis or to control cell division in neoplastic diseases such as breast cancer and non-Hodgkin's lymphoma.[A180322][L7144][L7147][L7150][L7180]
Due to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments.[L7180]
Methotrexate was granted FDA approval on 7 December 1953.[L7198]
Due to the toxic effects of methotrexate, it is indicated for treatment of some forms of arthritis and severe psoriasis only if first line treatment has failed or patients are intolerant of those treatments.[L7180]
Methotrexate was granted FDA approval on 7 December 1953.[L7198]
Properties:
View FDA drug labelsolid
Avg. mass: 454.44 Da
DrugBank indication
Methotrexate oral solution is indicated for pediatric acute lymphoblastic leukemia and pediatric polyarticular juvenile idiopathic arthritis.
[L7144]
Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis.
[L7147][L7150][L10457]
It has also been approved by the EMA for the treatment of adult patients requiring systemic therapy for moderate-to-severe plaque psoriasis.
[L48796]
Other formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma.
[L7180]
It is also used in the maintenance of acute lymphocytic leukemia.
[L7180]
Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma.
[L7180]
[L7144]
Methotrexate injections for subcutaneous use are indicated for severe active rheumatoid arthritis, polyarticular juvenile idiopathic arthritis and severe, recalcitrant, disabling psoriasis.
[L7147][L7150][L10457]
It has also been approved by the EMA for the treatment of adult patients requiring systemic therapy for moderate-to-severe plaque psoriasis.
[L48796]
Other formulations are indicated to treat gestational choriocarcinoma, chorioadenoma destruens, hydatiform mole, breast cancer, epidermoid cancer of the head and neck, advanced mycosis fungoides, lung cancer, and advanced non-Hodgkin's lymphoma.
[L7180]
It is also used in the maintenance of acute lymphocytic leukemia.
[L7180]
Methotrexate is also given before treatment with leucovorin to prolong relapse-free survival following surgical removal of a tumour in non-metastatic osteosarcoma.
[L7180]
Also known as(280)
4-amino-10-methylfolic acid
4-amino-N(10)-methylpteroylglutamic acid
Alpha-Methopterin
Amethopterin
Methotrexat
Méthotrexate
Methotrexate
Methotrexatum
Dosage forms(282)
Solution — 100 mg/1ml
Injection, solution (Parenteral) — 25 mg/1ml
Injection (Subcutaneous) — 10 mg/mL
Injection (Subcutaneous) — 20 mg/2.0mL
Injection (Subcutaneous)
Injection, solution (Subcutaneous) — 7.5 mg/0.75ml
Solution (Subcutaneous) — 25.000 mg
Tablet (Oral) — 2.780 mg
Molecular properties(19)
Drug interactions(1800)
Known interactions with other medications. Always consult a healthcare professional.
The risk or severity of adverse effects can be increased when Denosumab is combined with Methotrexate.
Peginterferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2a is combined with Methotrexate.
Interferon alfa-n1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n1 is combined with Methotrexate.
Interferon alfa-n3
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-n3 is combined with Methotrexate.
Peginterferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Peginterferon alfa-2b is combined with Methotrexate.
Interferon gamma-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon gamma-1b is combined with Methotrexate.
Interferon alfa-2a
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2a is combined with Methotrexate.
Gemtuzumab ozogamicin
Unknown severity
The risk or severity of adverse effects can be increased when Gemtuzumab ozogamicin is combined with Methotrexate.
Interferon beta-1b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon beta-1b is combined with Methotrexate.
Interferon alfacon-1
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfacon-1 is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Rituximab is combined with Methotrexate.
Basiliximab
Unknown severity
The risk or severity of adverse effects can be increased when Basiliximab is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Muromonab is combined with Methotrexate.
Ibritumomab tiuxetan
Unknown severity
The risk or severity of adverse effects can be increased when Ibritumomab tiuxetan is combined with Methotrexate.
Tositumomab
Unknown severity
The risk or severity of adverse effects can be increased when Tositumomab is combined with Methotrexate.
Alemtuzumab
Unknown severity
The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Alefacept is combined with Methotrexate.
Efalizumab
Unknown severity
The risk or severity of adverse effects can be increased when Efalizumab is combined with Methotrexate.
Antithymocyte immunoglobulin (rabbit)
Unknown severity
The risk or severity of adverse effects can be increased when Antithymocyte immunoglobulin (rabbit) is combined with Methotrexate.
Interferon alfa-2b
Unknown severity
The risk or severity of adverse effects can be increased when Interferon alfa-2b is combined with Methotrexate.
Daclizumab
Unknown severity
The risk or severity of adverse effects can be increased when Daclizumab is combined with Methotrexate.
Phenylalanine
Unknown severity
The risk or severity of adverse effects can be increased when Phenylalanine is combined with Methotrexate.
Bortezomib
Unknown severity
The risk or severity of adverse effects can be increased when Bortezomib is combined with Methotrexate.
Cladribine
Moderate
Methotrexate may increase the immunosuppressive activities of Cladribine.
Carmustine
Unknown severity
The risk or severity of adverse effects can be increased when Carmustine is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Amsacrine is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Bleomycin is combined with Methotrexate.
Chlorambucil
Unknown severity
The risk or severity of adverse effects can be increased when Chlorambucil is combined with Methotrexate.
Raltitrexed
Unknown severity
The risk or severity of adverse effects can be increased when Raltitrexed is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Mitomycin is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Vindesine is combined with Methotrexate.
Floxuridine
Unknown severity
The risk or severity of adverse effects can be increased when Floxuridine is combined with Methotrexate.
Tioguanine
Unknown severity
The risk or severity of adverse effects can be increased when Tioguanine is combined with Methotrexate.
Vinorelbine
Unknown severity
The risk or severity of adverse effects can be increased when Vinorelbine is combined with Methotrexate.
Dexrazoxane
Unknown severity
The risk or severity of adverse effects can be increased when Dexrazoxane is combined with Methotrexate.
Streptozocin
Unknown severity
The risk or severity of adverse effects can be increased when Streptozocin is combined with Methotrexate.
Trifluridine
Unknown severity
The risk or severity of adverse effects can be increased when Trifluridine is combined with Methotrexate.
Gemcitabine
Unknown severity
The risk or severity of adverse effects can be increased when Gemcitabine is combined with Methotrexate.
Epirubicin
Unknown severity
The risk or severity of adverse effects can be increased when Epirubicin is combined with Methotrexate.
Lenalidomide
Unknown severity
The risk or severity of adverse effects can be increased when Lenalidomide is combined with Methotrexate.
Altretamine
Unknown severity
The risk or severity of adverse effects can be increased when Altretamine is combined with Methotrexate.
Zidovudine
Unknown severity
The risk or severity of adverse effects can be increased when Zidovudine is combined with Methotrexate.
Oxaliplatin
Major
The risk or severity of nephrotoxicity can be increased when Oxaliplatin is combined with Methotrexate.
Vincristine
Unknown severity
The risk or severity of adverse effects can be increased when Vincristine is combined with Methotrexate.
Propylthiouracil
Unknown severity
The risk or severity of adverse effects can be increased when Propylthiouracil is combined with Methotrexate.
Pentostatin
Unknown severity
The risk or severity of adverse effects can be increased when Pentostatin is combined with Methotrexate.
The risk or severity of adverse effects can be increased when Methotrexate is combined with Linezolid.
Clofarabine
Unknown severity
The risk or severity of adverse effects can be increased when Methotrexate is combined with Clofarabine.
Fludrocortisone
Unknown severity
The risk or severity of adverse effects can be increased when Methotrexate is combined with Fludrocortisone.
Mycophenolate mofetil
Unknown severity
The risk or severity of adverse effects can be increased when Methotrexate is combined with Mycophenolate mofetil.
Showing 50 of 1800 interactions
Food & lifestyle interactions
Avoid Alcohol
Avoid alcohol.
Advice
Avoid milk and dairy products. Milk and dairy products reduce absorption.
Advice
Exercise caution with St. John's Wort.
Caffeine Notice
Limit caffeine intake. Caffeine may reduce the effectiveness of methotrexate.
Advice
Take with or without food.
Toxicity & overdose
The oral LD50 in rats is 135mg/kg and in mice is 146mg/kg.
[L7204]
Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding.
[L7180]
In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase.
[L7180]
[L7204]
Symptoms of overdose include hematologic and gastrointestinal reactions like leukopenia, thombocytopenia, anemia, pancytopenia, bone marrow suppression, mucositis, stomatitis, oral ulceration, nausea, vomiting, gastrointestinal ulceration, and gastrointestinal bleeding.
[L7180]
In the event of an overdose, patients should be treated with glucarpidase and not be given leucovorin for 2 hours before or after glucarpidase.
[L7180]
How it works
Mechanism of action
Methotrexate enters tissues and is converted to a methotrexate polyglutamate by folylpolyglutamate.[A180322]
Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase.[A180322] Inhibtion of nucleotide synthesis prevents cell division.
In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate.[A180322] This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.[A180322]
Methotrexate's mechanism of action is due to its inhibition of enzymes responsible for nucleotide synthesis including dihydrofolate reductase, thymidylate synthase, aminoimidazole caboxamide ribonucleotide transformylase (AICART), and amido phosphoribosyltransferase.[A180322] Inhibtion of nucleotide synthesis prevents cell division.
In rheumatoid arthritis, methotrexate polyglutamates inhibit AICART more than methotrexate.[A180322] This inhibition leads to accumulation of AICART ribonucleotide, which inhibits adenosine deaminase, leading to an accumulation of adenosine triphosphate and adenosine in the extracellular space, stimulating adenosine receptors, leading to anti-inflammatory action.[A180322]
Pharmacodynamics
Methotrexate inhibits enzymes responsible for nucleotide synthesis which prevents cell division and leads to anti-inflammatory actions.[A180322] It has a long duration of action and is generally given to patients once weekly.[A180322][L7144][L7147][L7150] Methotrexate has a narrow therapeutic index.[A180325]
Do not take methotrexate daily.[L7147][L7150]
Do not take methotrexate daily.[L7147][L7150]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Methotrexate has a bioavailability of 64-90%, though this decreases at oral doses above 25mg due to saturation of the carrier mediated transport of methotrexate..
[A180322]
Methotrexate has a Tmax of 1 to 2 hours.
[A180322]
oral doses of 10-15µg reach serum levels of 0.01-0.1µM.
[A180322]
[A180322]
Methotrexate has a Tmax of 1 to 2 hours.
[A180322]
oral doses of 10-15µg reach serum levels of 0.01-0.1µM.
[A180322]
Half-life
The half life of low dose methotrexate is 3 to 10 hours in adults.
[L7144]
The half life for high dose methotrexate is 8 to 15 hours.
[L7147]
Pediatric patients taking methotrexate for acute lymphoblastic anemia experience a terminal half life of 0.7 to 5.8 hours.
[L7144]
Pediatric patients taking methotrexate for juvenile idiopathic arthritis experience a half life of 0.9 to 2.3 hours.
[L7144]
[L7144]
The half life for high dose methotrexate is 8 to 15 hours.
[L7147]
Pediatric patients taking methotrexate for acute lymphoblastic anemia experience a terminal half life of 0.7 to 5.8 hours.
[L7144]
Pediatric patients taking methotrexate for juvenile idiopathic arthritis experience a half life of 0.9 to 2.3 hours.
[L7144]
Protein binding
Methotrexate is 46.5-54% bound to plasma proteins.
[A180322]
[A180322]
Volume of distribution
The volume of distribution of methotrexate at steady state is approximately 1L/kg.
[A180322]
[A180322]
Metabolism
Methotrexate is metabolized by folylpolyglutamate synthase to methotrexate polyglutamate in the liver as well as in tissues.
[A180322][L7180]
Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate.
[A180322][L7180]
A small amount of methotrexate is also converted to 7-hydroxymethotrexate.
[A180322][L7180]
[A180322][L7180]
Gamma-glutamyl hydrolase hydrolyzes the glutamyl chains of methotrexate polyglutamates converting them back to methotrexate.
[A180322][L7180]
A small amount of methotrexate is also converted to 7-hydroxymethotrexate.
[A180322][L7180]
Route of elimination
Methotrexate is >80% excreted as the unchanged drug and approximately 3% as the 7-hydroxylated metabolite.
[A180322]
Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile.
[A180322]
[A180322]
Methotrexate is primarily excreted in the urine with 8.7-26% of an intravenous dose appearing in the bile.
[A180322]
Clearance
Methotrexate clearance varies widely between patients and decreases with increasing doses.
[A180400]
Currently, predicting clearance of methotrexate is difficult and exceedingly high serum levels of methotrexate can still occur when all precautions are taken.
[A180400]
[A180400]
Currently, predicting clearance of methotrexate is difficult and exceedingly high serum levels of methotrexate can still occur when all precautions are taken.
[A180400]
Drug targets(5)
Proteins and enzymes this drug interacts with in the body
Thymidylate synthase
TYMS
inhibitor
Specific functionfolic acid binding
Cellular location
Nucleus
General function & pharmacology
Catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate (dUMP) to thymidine 5'-monophosphate (dTMP), using the cosubstrate, 5,10- methylenetetrahydrofolate (CH2H4folate) as a 1-carbon donor and reductant and contributes to the de novo mitochondrial thymidylate biosynthesis pathway
Bifunctional purine biosynthesis protein ATIC
ATIC
inhibitor
Specific functioncadherin binding
Cellular location
Cytoplasm, cytosol
General function & pharmacology
Bifunctional enzyme that catalyzes the last two steps of purine biosynthesis .
PMID:11948179 PMID:14756554
Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) .
PMID:10985775 PMID:11948179 PMID:9378707
Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction .
PMID:10985775
Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) .
PMID:11948179 PMID:14756554
Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias .
PMID:10985775
Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization PMID:25687571
PMID:11948179 PMID:14756554
Acts as a transformylase that incorporates a formyl group to the AMP analog AICAR (5-amino-1-(5-phospho-beta-D-ribosyl)imidazole-4-carboxamide) to produce the intermediate formyl-AICAR (FAICAR) .
PMID:10985775 PMID:11948179 PMID:9378707
Can use both 10-formyldihydrofolate and 10-formyltetrahydrofolate as the formyl donor in this reaction .
PMID:10985775
Also catalyzes the cyclization of FAICAR to inosine monophosphate (IMP) .
PMID:11948179 PMID:14756554
Is able to convert thio-AICAR to 6-mercaptopurine ribonucleotide, an inhibitor of purine biosynthesis used in the treatment of human leukemias .
PMID:10985775
Promotes insulin receptor/INSR autophosphorylation and is involved in INSR internalization PMID:25687571
Dihydrofolate reductase
DHFR
inhibitor
Specific functiondihydrofolate reductase activity
Cellular location
Mitochondrion
General function & pharmacology
Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis.
Binds its own mRNA and that of DHFR2
Binds its own mRNA and that of DHFR2
Reduced folate transporter
SLC19A1
modulator
Specific function2',3'-cyclic GMP-AMP binding
Cellular location
Cell membrane
General function & pharmacology
Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions .
PMID:10787414 PMID:15337749 PMID:16115875 PMID:22554803 PMID:31126740 PMID:31511694 PMID:32276275 PMID:36071163 PMID:36265513 PMID:36575193 PMID:7826387 PMID:9041240
Acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses .
PMID:31126740 PMID:31511694 PMID:36745868
Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates .
PMID:22554803 PMID:31126740 PMID:31511694
Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate .
PMID:10787414 PMID:14609557 PMID:22554803 PMID:36071163 PMID:36265513 PMID:36575193
Also mediates the import of antifolate drug methotrexate .
PMID:22554803 PMID:36071163 PMID:7615551 PMID:7641195 PMID:9767079
5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity PMID:22554803
PMID:10787414 PMID:15337749 PMID:16115875 PMID:22554803 PMID:31126740 PMID:31511694 PMID:32276275 PMID:36071163 PMID:36265513 PMID:36575193 PMID:7826387 PMID:9041240
Acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses .
PMID:31126740 PMID:31511694 PMID:36745868
Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates .
PMID:22554803 PMID:31126740 PMID:31511694
Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate .
PMID:10787414 PMID:14609557 PMID:22554803 PMID:36071163 PMID:36265513 PMID:36575193
Also mediates the import of antifolate drug methotrexate .
PMID:22554803 PMID:36071163 PMID:7615551 PMID:7641195 PMID:9767079
5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity PMID:22554803
Proton-coupled folate transporter
SLC46A1
modulator
Specific functionfolic acid binding
Cellular location
Cell membrane
General function & pharmacology
Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:19762432 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:31792273 PMID:32893190 PMID:34619546
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:32893190
Functions at acidic pH via alternate outward- and inward-open conformation states .
PMID:32893190 PMID:34040256
Protonation of residues in the outward open state primes the protein for transport .
PMID:34040256
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate .
PMID:34040256
Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases .
PMID:18524888 PMID:19762432 PMID:22345511 PMID:25608532 PMID:28802835 PMID:29326243 PMID:34040256 PMID:34619546
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes .
PMID:19074442
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine .
PMID:17156779
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells .
PMID:32621820
Hence, participates in the trafficking of heme and increases intracellular iron content PMID:32621820
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:19762432 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:31792273 PMID:32893190 PMID:34619546
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:32893190
Functions at acidic pH via alternate outward- and inward-open conformation states .
PMID:32893190 PMID:34040256
Protonation of residues in the outward open state primes the protein for transport .
PMID:34040256
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate .
PMID:34040256
Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases .
PMID:18524888 PMID:19762432 PMID:22345511 PMID:25608532 PMID:28802835 PMID:29326243 PMID:34040256 PMID:34619546
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes .
PMID:19074442
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine .
PMID:17156779
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells .
PMID:32621820
Hence, participates in the trafficking of heme and increases intracellular iron content PMID:32621820
Metabolizing enzymes(9)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
DHFRDihydrofolate reductase
substrate
AOX1Aldehyde oxidase
substrate
MTHFRMethylenetetrahydrofolate reductase (NADPH)
substrate
PGD6-phosphogluconate dehydrogenase, decarboxylating
inhibitor
FPGSFolylpolyglutamate synthase, mitochondrial
substrate
TYMSThymidylate synthase
substrate
ATICBifunctional purine biosynthesis protein ATIC
inhibitor
GGHGamma-glutamyl hydrolase
substrate
CYP3A4Cytochrome P450 3A4
substrate
Transporters(25)
Proteins that transport this drug across cell membranes
ATP-binding cassette sub-family C member 3
ABCC3
substrate
inhibitor
Specific functionABC-type bile acid transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes .
PMID:10359813 PMID:11581266 PMID:15083066
Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) .
PMID:11581266 PMID:15083066
Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable).
Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells PMID:10359813 PMID:11581266
PMID:10359813 PMID:11581266 PMID:15083066
Transports glucuronide conjugates such as bilirubin diglucuronide, estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) .
PMID:11581266 PMID:15083066
Transports also various bile salts (taurocholate, glycocholate, taurochenodeoxycholate-3-sulfate, taurolithocholate- 3-sulfate) (By similarity). Does not contribute substantially to bile salt physiology but provides an alternative route for the export of bile acids and glucuronides from cholestatic hepatocytes (By similarity). May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable).
Can confer resistance to various anticancer drugs, methotrexate, tenoposide and etoposide, by decreasing accumulation of these drugs in cells PMID:10359813 PMID:11581266
ATP-binding cassette sub-family C member 4
ABCC4
substrate
inhibitor
Specific function15-hydroxyprostaglandin dehydrogenase (NAD+) activity
Cellular location
Basolateral cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Transports a range of endogenous molecules that have a key role in cellular communication and signaling, including cyclic nucleotides such as cyclic AMP (cAMP) and cyclic GMP (cGMP), bile acids, steroid conjugates, urate, and prostaglandins .
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
PMID:11856762 PMID:12523936 PMID:12835412 PMID:12883481 PMID:15364914 PMID:15454390 PMID:16282361 PMID:17959747 PMID:18300232 PMID:26721430
Mediates the ATP-dependent efflux of glutathione conjugates such as leukotriene C4 (LTC4) and leukotriene B4 (LTB4) too. The presence of GSH is necessary for the ATP-dependent transport of LTB4, whereas GSH is not required for the transport of LTC4 .
PMID:17959747
Mediates the cotransport of bile acids with reduced glutathione (GSH) .
PMID:12523936 PMID:12883481 PMID:16282361
Transports a wide range of drugs and their metabolites, including anticancer, antiviral and antibiotics molecules .
PMID:11856762 PMID:12105214 PMID:15454390 PMID:17344354 PMID:18300232
Confers resistance to anticancer agents such as methotrexate PMID:11106685
Multidrug resistance-associated protein 1
ABCC1
substrate
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates export of organic anions and drugs from the cytoplasm .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export .
PMID:9281595
Hydrolyzes ATP with low efficiency .
PMID:16230346
Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation .
PMID:17050692
Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export .
PMID:36070769
Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway .
PMID:36070769
Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity).
Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells PMID:9426231
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotrexate, antiviral drugs and other xenobiotics .
PMID:10064732 PMID:11114332 PMID:16230346 PMID:7961706 PMID:9281595
Confers resistance to anticancer drugs by decreasing accumulation of drug in cells, and by mediating ATP- and GSH-dependent drug export .
PMID:9281595
Hydrolyzes ATP with low efficiency .
PMID:16230346
Catalyzes the export of sphingosine 1-phosphate from mast cells independently of their degranulation .
PMID:17050692
Participates in inflammatory response by allowing export of leukotriene C4 from leukotriene C4-synthesizing cells (By similarity). Mediates ATP-dependent, GSH-independent cyclic GMP-AMP (cGAMP) export .
PMID:36070769
Thus, by limiting intracellular cGAMP concentrations negatively regulates the cGAS-STING pathway .
PMID:36070769
Exports S-geranylgeranyl-glutathione (GGG) in lymphoid cells and stromal compartments of lymphoid organs. ABCC1 (via extracellular transport) with GGT5 (via GGG catabolism) establish GGG gradients within lymphoid tissues to position P2RY8-positive lymphocytes at germinal centers in lymphoid follicles and restrict their chemotactic transmigration from blood vessels to the bone marrow parenchyma (By similarity).
Mediates basolateral export of GSH-conjugated R- and S-prostaglandin A2 diastereomers in polarized epithelial cells PMID:9426231
Solute carrier family 22 member 6
SLC22A6
substrate
inhibitor
Specific functionalpha-ketoglutarate transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Secondary active transporter that functions as a Na(+)-independent organic anion (OA)/dicarboxylate antiporter where the uptake of one molecule of OA into the cell is coupled with an efflux of one molecule of intracellular dicarboxylate such as 2-oxoglutarate or glutarate .
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
PMID:11669456 PMID:11907186 PMID:14675047 PMID:22108572 PMID:23832370 PMID:28534121 PMID:9950961
Mediates the uptake of OA across the basolateral side of proximal tubule epithelial cells, thereby contributing to the renal elimination of endogenous OA from the systemic circulation into the urine .
PMID:9887087
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
Transports prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may contribute to their renal excretion .
PMID:11907186
Also mediates the uptake of cyclic nucleotides such as cAMP and cGMP .
PMID:26377792
Involved in the transport of neuroactive tryptophan metabolites kynurenate (KYNA) and xanthurenate (XA) and may contribute to their secretion from the brain .
PMID:22108572 PMID:23832370
May transport glutamate .
PMID:26377792
Also involved in the disposition of uremic toxins and potentially toxic xenobiotics by the renal organic anion secretory pathway, helping reduce their undesired toxicological effects on the body .
PMID:11669456 PMID:14675047
Uremic toxins include the indoxyl sulfate (IS), hippurate/N-benzoylglycine (HA), indole acetate (IA), 3-carboxy-4- methyl-5-propyl-2-furanpropionate (CMPF) and urate .
PMID:14675047 PMID:26377792
Xenobiotics include the mycotoxin ochratoxin (OTA) .
PMID:11669456
May also contribute to the transport of organic compounds in testes across the blood-testis-barrier PMID:35307651
ATP-binding cassette sub-family C member 10
ABCC10
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds, and xenobiotics from cells. Lipophilic anion transporter that mediates ATP-dependent transport of glucuronide conjugates such as estradiol-17-beta-o-glucuronide and GSH conjugates such as leukotriene C4 (LTC4) .
PMID:12527806 PMID:15256465
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel .
PMID:15256465 PMID:23087055
Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP PMID:12527806
PMID:12527806 PMID:15256465
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Mediates multidrug resistance (MDR) in cancer cells by preventing the intracellular accumulation of certain antitumor drugs, such as, docetaxel and paclitaxel .
PMID:15256465 PMID:23087055
Does not transport glycocholic acid, taurocholic acid, MTX, folic acid, cAMP, or cGMP PMID:12527806
Organic anion transporter 3
SLC22A8
substrate
inhibitor
Specific functionorganic anion transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Functions as an organic anion/dicarboxylate exchanger that couples organic anion uptake indirectly to the sodium gradient .
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
PMID:14586168 PMID:15644426 PMID:15846473 PMID:16455804 PMID:31553721
Transports organic anions such as estrone 3-sulfate (E1S) and urate in exchange for dicarboxylates such as glutarate or ketoglutarate (2-oxoglutarate) .
PMID:14586168 PMID:15846473 PMID:15864504 PMID:22108572 PMID:23832370
Plays an important role in the excretion of endogenous and exogenous organic anions, especially from the kidney and the brain .
PMID:11306713 PMID:14586168 PMID:15846473
E1S transport is pH- and chloride-dependent and may also involve E1S/cGMP exchange .
PMID:26377792
Responsible for the transport of prostaglandin E2 (PGE2) and prostaglandin F2(alpha) (PGF2(alpha)) in the basolateral side of the renal tubule .
PMID:11907186
Involved in the transport of neuroactive tryptophan metabolites kynurenate and xanthurenate .
PMID:22108572 PMID:23832370
Functions as a biopterin transporters involved in the uptake and the secretion of coenzymes tetrahydrobiopterin (BH4), dihydrobiopterin (BH2) and sepiapterin to urine, thereby determining baseline levels of blood biopterins .
PMID:28534121
May be involved in the basolateral transport of steviol, a metabolite of the popular sugar substitute stevioside .
PMID:15644426
May participate in the detoxification/ renal excretion of drugs and xenobiotics, such as the histamine H(2)-receptor antagonists fexofenadine and cimetidine, the antibiotic benzylpenicillin (PCG), the anionic herbicide 2,4-dichloro-phenoxyacetate (2,4-D), the diagnostic agent p-aminohippurate (PAH), the antiviral acyclovir (ACV), and the mycotoxin ochratoxin (OTA), by transporting these exogenous organic anions across the cell membrane in exchange for dicarboxylates such as 2-oxoglutarate .
PMID:11669456 PMID:15846473 PMID:16455804
Contributes to the renal uptake of potent uremic toxins (indoxyl sulfate (IS), indole acetate (IA), hippurate/N-benzoylglycine (HA) and 3-carboxy-4-methyl-5-propyl-2-furanpropionate (CMPF)), pravastatin, PCG, E1S and dehydroepiandrosterone sulfate (DHEAS), and is partly involved in the renal uptake of temocaprilat (an angiotensin-converting enzyme (ACE) inhibitor) .
PMID:14675047
May contribute to the release of cortisol in the adrenals .
PMID:15864504
Involved in one of the detoxification systems on the choroid plexus (CP), removes substrates such as E1S or taurocholate (TC), PCG, 2,4-D and PAH, from the cerebrospinal fluid (CSF) to the blood for eventual excretion in urine and bile (By similarity). Also contributes to the uptake of several other organic compounds such as the prostanoids prostaglandin E(2) and prostaglandin F(2-alpha), L-carnitine, and the therapeutic drugs allopurinol, 6-mercaptopurine (6-MP) and 5-fluorouracil (5-FU) (By similarity). Mediates the transport of PAH, PCG, and the statins pravastatin and pitavastatin, from the cerebrum into the blood circulation across the blood-brain barrier (BBB).
In summary, plays a role in the efflux of drugs and xenobiotics, helping reduce their undesired toxicological effects on the body (By similarity)
ATP-binding cassette sub-family C member 2
ABCC2
substrate
inhibitor
Specific functionABC-type glutathione S-conjugate transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that binds and hydrolyzes ATP to enable active transport of various substrates including many drugs, toxicants and endogenous compound across cell membranes. Transports a wide variety of conjugated organic anions such as sulfate-, glucuronide- and glutathione (GSH)-conjugates of endo- and xenobiotics substrates .
PMID:10220572 PMID:10421658 PMID:11500505 PMID:16332456
Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification .
PMID:10421658
Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 .
PMID:11500505
Transports sulfated bile salt such as taurolithocholate sulfate .
PMID:16332456
Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors .
PMID:10220572 PMID:11500505 PMID:12441801
Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine PMID:10220572 PMID:11500505
PMID:10220572 PMID:10421658 PMID:11500505 PMID:16332456
Mediates hepatobiliary excretion of mono- and bis-glucuronidated bilirubin molecules and therefore play an important role in bilirubin detoxification .
PMID:10421658
Also mediates hepatobiliary excretion of others glucuronide conjugates such as 17beta-estradiol 17-glucosiduronic acid and leukotriene C4 .
PMID:11500505
Transports sulfated bile salt such as taurolithocholate sulfate .
PMID:16332456
Transports various anticancer drugs, such as anthracycline, vinca alkaloid and methotrexate and HIV-drugs such as protease inhibitors .
PMID:10220572 PMID:11500505 PMID:12441801
Confers resistance to several anti-cancer drugs including cisplatin, doxorubicin, epirubicin, methotrexate, etoposide and vincristine PMID:10220572 PMID:11500505
ATP-dependent translocase ABCB1
ABCB1
substrate
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Translocates drugs and phospholipids across the membrane .
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
PMID:2897240 PMID:35970996 PMID:8898203 PMID:9038218 PMID:35507548
Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins .
PMID:8898203
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells PMID:2897240 PMID:35970996 PMID:9038218
Solute carrier organic anion transporter family member 1A2
SLCO1A2
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Na(+)-independent transporter that mediates the cellular uptake of a broad range of organic anions such as the endogenous bile salts cholate and deoxycholate, either in their unconjugated or conjugated forms (taurocholate and glycocholate), at the plasmam membrane .
PMID:19129463 PMID:7557095
Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) .
PMID:11159893 PMID:12568656 PMID:19129463 PMID:23918469 PMID:25560245 PMID:9539145
Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision .
PMID:25560245
Involved in the uptake of clinically used drugs .
PMID:17301733 PMID:20686826 PMID:27777271
Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) .
PMID:19129463 PMID:20358049
Also transports prostaglandin E2 .
PMID:19129463
Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:19129463 PMID:7557095
Responsible for intestinal absorption of bile acids (By similarity). Transports dehydroepiandrosterone 3-sulfate (DHEAS), a major circulating steroid secreted by the adrenal cortex, as well as estrone 3-sulfate and 17beta-estradiol 17-O-(beta-D-glucuronate) .
PMID:11159893 PMID:12568656 PMID:19129463 PMID:23918469 PMID:25560245 PMID:9539145
Mediates apical uptake of all-trans-retinol (atROL) across human retinal pigment epithelium, which is essential to maintaining the integrity of the visual cycle and thus vision .
PMID:25560245
Involved in the uptake of clinically used drugs .
PMID:17301733 PMID:20686826 PMID:27777271
Capable of thyroid hormone transport (both T3 or 3,3',5'-triiodo-L-thyronine, and T4 or L-tyroxine) .
PMID:19129463 PMID:20358049
Also transports prostaglandin E2 .
PMID:19129463
Plays roles in blood-brain and -cerebrospinal fluid barrier transport of organic anions and signal mediators, and in hormone uptake by neural cells (By similarity). May also play a role in the reuptake of neuropeptides such as substance P/TAC1 and vasoactive intestinal peptide/VIP released from retinal neurons .
PMID:25132355
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
Shows a pH-sensitive substrate specificity which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Monocarboxylate transporter 1
SLC16A1
substrate
Specific functioncarboxylic acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Bidirectional proton-coupled monocarboxylate transporter .
PMID:12946269 PMID:32946811 PMID:33333023
Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH .
PMID:12946269 PMID:33333023
The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (By similarity).
Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart .
PMID:32946811
Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition PMID:33333023
PMID:12946269 PMID:32946811 PMID:33333023
Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH .
PMID:12946269 PMID:33333023
The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity). Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (By similarity).
Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart .
PMID:32946811
Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 309-Asp is essential for the conformational transition PMID:33333023
ATP-binding cassette sub-family C member 11
ABCC11
substrate
Specific functionABC-type bile acid transporter activity
Cellular location
Cell membrane
General function & pharmacology
ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes physiological compounds and xenobiotics from cells. Plays a role in physiological processes involving bile acids, conjugated steroids and cyclic nucleotides, including cAMP and cGMP .
PMID:12764137 PMID:15537867
Mediates the ATP-dependent efflux of a range of physiological lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates, such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate .
PMID:15537867 PMID:16359813 PMID:25896536
Plays a role in the transport of earwax components .
PMID:16444273 PMID:19383836
Participates in the secretion of odorants and their precursors from the apocrine sweat glands, including the secretion of glutamine conjugates, as well as the Cys-Gly-(S) conjugates of 3-methyl-3-sulfanyl-hexanol .
PMID:19710689
Involved in the cellular extrusion of nucleotide analogs, hence confering resistance to various drugs, including clinically relevant drugs such as 5-fluorouracil (5-FU) and methotrexate PMID:12764137 PMID:15537867 PMID:25896536
PMID:12764137 PMID:15537867
Mediates the ATP-dependent efflux of a range of physiological lipophilic anions, including the glutathione S-conjugates leukotriene C4 and dinitrophenyl S-glutathione, steroid sulfates, such as dehydroepiandrosterone 3-sulfate (DHEAS) and estrone 3-sulfate, glucuronides such as estradiol 17-beta-D-glucuronide (E(2)17betaG), the monoanionic bile acids glycocholate and taurocholate, and methotrexate .
PMID:15537867 PMID:16359813 PMID:25896536
Plays a role in the transport of earwax components .
PMID:16444273 PMID:19383836
Participates in the secretion of odorants and their precursors from the apocrine sweat glands, including the secretion of glutamine conjugates, as well as the Cys-Gly-(S) conjugates of 3-methyl-3-sulfanyl-hexanol .
PMID:19710689
Involved in the cellular extrusion of nucleotide analogs, hence confering resistance to various drugs, including clinically relevant drugs such as 5-fluorouracil (5-FU) and methotrexate PMID:12764137 PMID:15537867 PMID:25896536
Solute carrier organic anion transporter family member 1B3
SLCO1B3
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
PMID:10779507 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (17-beta-glucuronosyl estradiol, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate), as well as eicosanoid leukotriene C4, prostaglandin E2 and L-thyroxine (T4) .
PMID:10779507 PMID:11159893 PMID:12568656 PMID:15159445 PMID:17412826 PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions .
PMID:19129463
Shows a pH-sensitive substrate specificity towards sulfated steroids, taurocholate and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Involved in the clearance of bile acids and organic anions from the liver .
PMID:22232210
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins) such as pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:15159445
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drugs methotrexate and paclitaxel .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver PMID:16624871 PMID:16627748
Solute carrier family 22 member 11
SLC22A11
substrate
Specific functionorganic anion transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Antiporter that mediates the transport of conjugated steroids and other specific organic anions at the basal membrane of syncytiotrophoblast and at the apical membrane of proximal tubule epithelial cells, in exchange for anionic compounds .
PMID:10660625 PMID:11907186 PMID:15037815 PMID:15102942 PMID:15291761 PMID:15576633 PMID:17229912 PMID:18501590 PMID:26277985 PMID:28027879
May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus .
PMID:12409283
Maybe also be involved in placental urate homeostasis .
PMID:17229912
Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates .
PMID:15037815 PMID:17229912
Organic anion glutarate acts as conteranion for E1S renal uptake .
PMID:15037815 PMID:17229912
Possible transport mode may also include DHEA-S/E1S exchange .
PMID:28027879
Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) .
PMID:17229912
Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion .
PMID:11907186
Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A .
PMID:10660625 PMID:26277985
Mediates the unidirectional efflux of glutamate and aspartate .
PMID:28027879
Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S PMID:26277985
PMID:10660625 PMID:11907186 PMID:15037815 PMID:15102942 PMID:15291761 PMID:15576633 PMID:17229912 PMID:18501590 PMID:26277985 PMID:28027879
May be responsible for placental absorption of fetal-derived steroid sulfates such as estrone sulfate (E1S) and the steroid hormone precursor dehydroepiandrosterone sulfate (DHEA-S), as well as clearing waste products and xenobiotics from the fetus .
PMID:12409283
Maybe also be involved in placental urate homeostasis .
PMID:17229912
Facilitates the renal reabsorption of organic anions such as urate and derived steroid sulfates .
PMID:15037815 PMID:17229912
Organic anion glutarate acts as conteranion for E1S renal uptake .
PMID:15037815 PMID:17229912
Possible transport mode may also include DHEA-S/E1S exchange .
PMID:28027879
Also interacts with inorganic anions such as chloride and hydroxyl ions, therefore possible transport modes may include E1S/Cl(-), E1S/OH(-), urate/Cl(-) and urate/OH(-) .
PMID:17229912
Also mediates the transport of prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) and may be involved in their renal excretion .
PMID:11907186
Also able to uptake anionic drugs, diuretics, bile salts and ochratoxin A .
PMID:10660625 PMID:26277985
Mediates the unidirectional efflux of glutamate and aspartate .
PMID:28027879
Glutamate efflux down its transmembrane gradient may drive SLC22A11/OAT4-mediated placental uptake of E1S PMID:26277985
Solute carrier organic anion transporter family member 1C1
SLCO1C1
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Cell membrane
General function & pharmacology
Mediates the Na(+)-independent high affinity transport of organic anions such as the thyroid hormones L-thyroxine (T4), L-thyroxine sulfate (T4S), and 3,3',5'-triiodo-L-thyronine (reverse T3, rT3) at the plasma membrane .
PMID:12351693 PMID:18566113 PMID:19129463
Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases .
PMID:18566113
Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases .
PMID:18566113
Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency .
PMID:12351693 PMID:19129463
Transports T4 and E1S in a pH-insensitive manner .
PMID:19129463
Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain PMID:30296914
PMID:12351693 PMID:18566113 PMID:19129463
Regulates T4 levels in different brain regions by transporting T4, and also by serving as an export pump for T4S, which is a source of T4 after hydrolysis by local sulfatases .
PMID:18566113
Increases the access of these substrates to the intracellular sites where they are metabolized by the deiodinases .
PMID:18566113
Other potential substrates, such as triiodothyronine (T3), 17-beta-glucuronosyl estradiol (17beta-estradiol 17-O-(beta-D-glucuronate)), estrone-3-sulfate (E1S) and sulfobromophthalein (BSP) are transported with much lower efficiency .
PMID:12351693 PMID:19129463
Transports T4 and E1S in a pH-insensitive manner .
PMID:19129463
Facilitates the transport of thyroid hormones across the blood-brain barrier and into glia and neuronal cells in the brain PMID:30296914
Solute carrier organic anion transporter family member 3A1
SLCO3A1
substrate
Specific functionorganic anion transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Putative organic anion antiporter with apparent broad substrate specificity. Recognizes various substrates including thyroid hormone L-thyroxine, prostanoids such as prostaglandin E1 and E2, bile acids such as taurocholate, glycolate and glycochenodeoxycholate and peptide hormones such as L-arginine vasopressin, likely operating in a tissue-specific manner .
PMID:10873595 PMID:14631946 PMID:16971491 PMID:19129463 PMID:30063921
The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable)
PMID:10873595 PMID:14631946 PMID:16971491 PMID:19129463 PMID:30063921
The transport mechanism, its electrogenicity and potential tissue-specific counterions remain to be elucidated (Probable)
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
Specific functionABC-type xenobiotic transporter activity
Cellular location
Cell membrane
General function & pharmacology
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells .
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
PMID:11306452 PMID:12958161 PMID:19506252 PMID:20705604 PMID:28554189 PMID:30405239 PMID:31003562
Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme .
PMID:20705604 PMID:23189181
Also mediates the efflux of sphingosine-1-P from cells .
PMID:20110355
Acts as a urate exporter functioning in both renal and extrarenal urate excretion .
PMID:19506252 PMID:20368174 PMID:22132962 PMID:31003562 PMID:36749388
In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates .
PMID:12682043 PMID:28554189 PMID:30405239
Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity).
Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux .
PMID:11306452 PMID:12477054 PMID:15670731 PMID:18056989 PMID:31254042
In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity).
In inflammatory macrophages, exports itaconate from the cytosol to the extracellular compartment and limits the activation of TFEB-dependent lysosome biogenesis involved in antibacterial innate immune response
Solute carrier family 22 member 7
SLC22A7
substrate
Specific functionalpha-ketoglutarate transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Functions as a Na(+)-independent bidirectional multispecific transporter .
PMID:11327718 PMID:18216183 PMID:21446918 PMID:28945155
Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively .
PMID:11327718 PMID:25904762
Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates .
PMID:11327718 PMID:18216183 PMID:26377792 PMID:28945155
Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways .
PMID:18216183 PMID:26377792
Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood .
PMID:21446918
Involved in renal secretion and possible reabsorption of creatinine .
PMID:25904762 PMID:28945155
Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate .
PMID:11327718 PMID:26377792
Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified PMID:26377792
PMID:11327718 PMID:18216183 PMID:21446918 PMID:28945155
Contributes to the renal and hepatic elimination of endogenous organic compounds from the systemic circulation into the urine and bile, respectively .
PMID:11327718 PMID:25904762
Capable of transporting a wide range of purine and pyrimidine nucleobases, nucleosides and nucleotides, with cGMP, 2'deoxyguanosine and GMP being the preferred substrates .
PMID:11327718 PMID:18216183 PMID:26377792 PMID:28945155
Functions as a pH- and chloride-independent cGMP bidirectional facilitative transporter that can regulate both intracellular and extracellular levels of cGMP and may be involved in cGMP signaling pathways .
PMID:18216183 PMID:26377792
Mediates orotate/glutamate bidirectional exchange and most likely display a physiological role in hepatic release of glutamate into the blood .
PMID:21446918
Involved in renal secretion and possible reabsorption of creatinine .
PMID:25904762 PMID:28945155
Able to uptake prostaglandin E2 (PGE2) and may contribute to PGE2 renal excretion (Probable). Also transports alpha-ketoglutarate and urate .
PMID:11327718 PMID:26377792
Apart from the orotate/glutamate exchange, the counterions for the uptake of other SLC22A7/OAT2 substrates remain to be identified PMID:26377792
Proton-coupled folate transporter
SLC46A1
substrate
inhibitor
Specific functionfolic acid binding
Cellular location
Cell membrane
General function & pharmacology
Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:19762432 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:31792273 PMID:32893190 PMID:34619546
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:32893190
Functions at acidic pH via alternate outward- and inward-open conformation states .
PMID:32893190 PMID:34040256
Protonation of residues in the outward open state primes the protein for transport .
PMID:34040256
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate .
PMID:34040256
Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases .
PMID:18524888 PMID:19762432 PMID:22345511 PMID:25608532 PMID:28802835 PMID:29326243 PMID:34040256 PMID:34619546
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes .
PMID:19074442
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine .
PMID:17156779
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells .
PMID:32621820
Hence, participates in the trafficking of heme and increases intracellular iron content PMID:32621820
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:19762432 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:31792273 PMID:32893190 PMID:34619546
Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus .
PMID:17129779 PMID:17446347 PMID:17475902 PMID:19389703 PMID:25504888 PMID:29344585 PMID:30858177 PMID:31494288 PMID:32893190
Functions at acidic pH via alternate outward- and inward-open conformation states .
PMID:32893190 PMID:34040256
Protonation of residues in the outward open state primes the protein for transport .
PMID:34040256
Binding of folate promotes breaking of salt bridge network and subsequent closure of the extracellular gate, leading to the inward-open state and release of protons and folate .
PMID:34040256
Also able to transport antifolate drugs, such as methotrexate and pemetrexed, which are established treatments for cancer and autoimmune diseases .
PMID:18524888 PMID:19762432 PMID:22345511 PMID:25608532 PMID:28802835 PMID:29326243 PMID:34040256 PMID:34619546
Involved in FOLR1-mediated endocytosis by serving as a route of export of folates from acidified endosomes .
PMID:19074442
Also acts as a lower-affinity, pH-independent heme carrier protein and constitutes the main importer of heme in the intestine .
PMID:17156779
Imports heme in the retina and retinal pigment epithelium, in neurons of the hippocampus, in hepatocytes and in the renal epithelial cells .
PMID:32621820
Hence, participates in the trafficking of heme and increases intracellular iron content PMID:32621820
Solute carrier organic anion transporter family member 1B1
SLCO1B1
substrate
Specific functionbile acid transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the Na(+)-independent uptake of organic anions .
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
PMID:10358072 PMID:15159445 PMID:17412826
Shows broad substrate specificity, can transport both organic anions such as bile acid taurocholate (cholyltaurine) and conjugated steroids (dehydroepiandrosterone 3-sulfate, 17-beta-glucuronosyl estradiol, and estrone 3-sulfate), as well as eicosanoids (prostaglandin E2, thromboxane B2, leukotriene C4, and leukotriene E4), and thyroid hormones (T4/L-thyroxine, and T3/3,3',5'-triiodo-L-thyronine) .
PMID:10358072 PMID:10601278 PMID:10873595 PMID:11159893 PMID:12196548 PMID:12568656 PMID:15159445 PMID:15970799 PMID:16627748 PMID:17412826 PMID:19129463 PMID:26979622
Can take up bilirubin glucuronides from plasma into the liver, contributing to the detoxification-enhancing liver-blood shuttling loop .
PMID:22232210
Involved in the clearance of endogenous and exogenous substrates from the liver .
PMID:10358072 PMID:10601278
Transports coproporphyrin I and III, by-products of heme synthesis, and may be involved in their hepatic disposition .
PMID:26383540
May contribute to regulate the transport of organic compounds in testes across the blood-testis-barrier (Probable). Can transport HMG-CoA reductase inhibitors (also known as statins), such as pravastatin and pitavastatin, a clinically important class of hypolipidemic drugs .
PMID:10601278 PMID:15159445 PMID:15970799
May play an important role in plasma and tissue distribution of the structurally diverse chemotherapeutic drug methotrexate .
PMID:23243220
May also transport antihypertension agents, such as the angiotensin-converting enzyme (ACE) inhibitor prodrug enalapril, and the highly selective angiotensin II AT1-receptor antagonist valsartan, in the liver .
PMID:16624871 PMID:16627748
Shows a pH-sensitive substrate specificity towards prostaglandin E2 and T4 which may be ascribed to the protonation state of the binding site and leads to a stimulation of substrate transport in an acidic microenvironment .
PMID:19129463
Hydrogencarbonate/HCO3(-) acts as the probable counteranion that exchanges for organic anions PMID:19129463
Solute carrier organic anion transporter family member 4C1
SLCO4C1
Specific functionorganic anion transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Mediates the transport of organic anions such as steroids (estrone 3-sulfate, chenodeoxycholate, glycocholate) and thyroid hormones (3,3',5-triiodo-L-thyronine (T3), L-thyroxine (T4)), in the kidney .
PMID:14993604 PMID:19129463 PMID:20610891
Capable of transporting cAMP and pharmacological substances such as digoxin, ouabain and methotrexate .
PMID:14993604
Transport is independent of sodium, chloride ion, and ATP .
PMID:14993604
Transport activity is stimulated by an acidic extracellular environment due to increased substrate affinity to the transporter .
PMID:19129463
The driving force for this transport activity is currently not known (By similarity). The role of hydrogencarbonate (HCO3(-), bicarbonate) as the probable counteranion that exchanges for organic anions is still not well defined .
PMID:19129463
Functions as an uptake transporter at the apical membrane, suggesting a role in renal reabsorption (By similarity). Involved in the renal secretion of the uremic toxin ADMA (N(omega),N(omega)-dimethyl-L-arginine or asymmetrical dimethylarginine), which is associated to cardiovascular events and mortality, and the structurally related amino acids L-arginine and L-homoarginine (a cardioprotective biomarker) .
PMID:30865704
Can act bidirectionally, suggesting a dual protective role of this transport protein; exporting L-homoarginine after being synthesized in proximal tubule cells, and mediating uptake of ADMA from the blood into proximal tubule cells where it is degraded by the enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) .
PMID:30865704 PMID:32642843
May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells (By similarity).
This ion-transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation (By similarity). May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg (By similarity)
PMID:14993604 PMID:19129463 PMID:20610891
Capable of transporting cAMP and pharmacological substances such as digoxin, ouabain and methotrexate .
PMID:14993604
Transport is independent of sodium, chloride ion, and ATP .
PMID:14993604
Transport activity is stimulated by an acidic extracellular environment due to increased substrate affinity to the transporter .
PMID:19129463
The driving force for this transport activity is currently not known (By similarity). The role of hydrogencarbonate (HCO3(-), bicarbonate) as the probable counteranion that exchanges for organic anions is still not well defined .
PMID:19129463
Functions as an uptake transporter at the apical membrane, suggesting a role in renal reabsorption (By similarity). Involved in the renal secretion of the uremic toxin ADMA (N(omega),N(omega)-dimethyl-L-arginine or asymmetrical dimethylarginine), which is associated to cardiovascular events and mortality, and the structurally related amino acids L-arginine and L-homoarginine (a cardioprotective biomarker) .
PMID:30865704
Can act bidirectionally, suggesting a dual protective role of this transport protein; exporting L-homoarginine after being synthesized in proximal tubule cells, and mediating uptake of ADMA from the blood into proximal tubule cells where it is degraded by the enzyme dimethylarginine dimethylaminohydrolase 1 (DDAH1) .
PMID:30865704 PMID:32642843
May be involved in sperm maturation by enabling directed movement of organic anions and compounds within or between cells (By similarity).
This ion-transporting process is important to maintain the strict epididymal homeostasis necessary for sperm maturation (By similarity). May have a role in secretory functions since seminal vesicle epithelial cells are assumed to secrete proteins involved in decapacitation by modifying surface proteins to facilitate the acquisition of the ability to fertilize the egg (By similarity)
Reduced folate transporter
SLC19A1
substrate
Specific function2',3'-cyclic GMP-AMP binding
Cellular location
Cell membrane
General function & pharmacology
Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions .
PMID:10787414 PMID:15337749 PMID:16115875 PMID:22554803 PMID:31126740 PMID:31511694 PMID:32276275 PMID:36071163 PMID:36265513 PMID:36575193 PMID:7826387 PMID:9041240
Acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses .
PMID:31126740 PMID:31511694 PMID:36745868
Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates .
PMID:22554803 PMID:31126740 PMID:31511694
Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate .
PMID:10787414 PMID:14609557 PMID:22554803 PMID:36071163 PMID:36265513 PMID:36575193
Also mediates the import of antifolate drug methotrexate .
PMID:22554803 PMID:36071163 PMID:7615551 PMID:7641195 PMID:9767079
5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity PMID:22554803
PMID:10787414 PMID:15337749 PMID:16115875 PMID:22554803 PMID:31126740 PMID:31511694 PMID:32276275 PMID:36071163 PMID:36265513 PMID:36575193 PMID:7826387 PMID:9041240
Acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytosol, and its linkage isomer 3'-3'-cGAMP, thus playing a role in triggering larger immune responses .
PMID:31126740 PMID:31511694 PMID:36745868
Mechanistically, acts as a secondary active transporter, which exports intracellular organic anions down their concentration gradients to facilitate the uptake of its substrates .
PMID:22554803 PMID:31126740 PMID:31511694
Has high affinity for N5-methyltetrahydrofolate, the predominant circulating form of folate .
PMID:10787414 PMID:14609557 PMID:22554803 PMID:36071163 PMID:36265513 PMID:36575193
Also mediates the import of antifolate drug methotrexate .
PMID:22554803 PMID:36071163 PMID:7615551 PMID:7641195 PMID:9767079
5-amino-4-imidazolecarboxamide riboside (AICAR), when phosphorylated to AICAR monophosphate, can serve as an organic anion for antiporter activity PMID:22554803
Folate receptor alpha
FOLR1
substrate
Specific functionfolic acid binding
Cellular location
Cell membrane
General function & pharmacology
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells .
PMID:19074442 PMID:23851396 PMID:23934049 PMID:2527252 PMID:8033114 PMID:8567728
Has high affinity for folate and folic acid analogs at neutral pH .
PMID:23851396 PMID:23934049 PMID:2527252 PMID:8033114 PMID:8567728
Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release .
PMID:8567728
Required for normal embryonic development and normal cell proliferation (By similarity)
PMID:19074442 PMID:23851396 PMID:23934049 PMID:2527252 PMID:8033114 PMID:8567728
Has high affinity for folate and folic acid analogs at neutral pH .
PMID:23851396 PMID:23934049 PMID:2527252 PMID:8033114 PMID:8567728
Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release .
PMID:8567728
Required for normal embryonic development and normal cell proliferation (By similarity)
Folate receptor beta
FOLR2
substrate
Specific functionfolic acid binding
Cellular location
Cell membrane
General function & pharmacology
Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells. Has high affinity for folate and folic acid analogs at neutral pH. Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly reduces its affinity for folates and mediates their release
Solute carrier family 15 member 1
SLC15A1
substrate
Specific functiondipeptide transmembrane transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
Electrogenic proton-coupled amino-acid transporter that transports oligopeptides of 2 to 4 amino acids with a preference for dipeptides. Transports neutral and monovalently charged peptides with a proton to peptide stoichiometry of 1:1 or 2:1 (By similarity) .
PMID:15521010 PMID:18367661 PMID:19685173 PMID:26320580 PMID:7896779 PMID:8914574 PMID:9835627
Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (By similarity). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system PMID:15521010 PMID:9835627
PMID:15521010 PMID:18367661 PMID:19685173 PMID:26320580 PMID:7896779 PMID:8914574 PMID:9835627
Primarily responsible for the absorption of dietary di- and tripeptides from the small intestinal lumen (By similarity). Mediates transepithelial transport of muramyl and N-formylated bacterial dipeptides contributing to recognition of pathogenic bacteria by the mucosal immune system PMID:15521010 PMID:9835627
Proton-coupled amino acid transporter 1
SLC36A1
substrate
Specific functionABC-type taurine transporter transporter activity
Cellular location
Cell membrane
General function & pharmacology
Electrogenic proton/amino acid symporter with selectivity for small apolar L-amino acids, their D-enantiomers and selected amino acid derivatives such as 4-aminobutanoate/GABA .
PMID:12527723 PMID:12809675 PMID:19549785
May be involved in the efflux from the lysosomal compartment of neutral amino acids resulting from proteolysis (By similarity). May play a role in specifying sites for exocytosis in neurons (By similarity)
PMID:12527723 PMID:12809675 PMID:19549785
May be involved in the efflux from the lysosomal compartment of neutral amino acids resulting from proteolysis (By similarity). May play a role in specifying sites for exocytosis in neurons (By similarity)
Carriers(1)
Proteins that carry this drug through the body
Albumin
ALB
binder
Specific functionantioxidant activity
Cellular location
Secreted
General function & pharmacology
Binds water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs (Probable). Its main function is the regulation of the colloidal osmotic pressure of blood (Probable). Major zinc transporter in plasma, typically binds about 80% of all plasma zinc .
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
PMID:19021548
Major calcium and magnesium transporter in plasma, binds approximately 45% of circulating calcium and magnesium in plasma (By similarity).
Potentially has more than two calcium-binding sites and might additionally bind calcium in a non-specific manner (By similarity). The shared binding site between zinc and calcium at residue Asp-273 suggests a crosstalk between zinc and calcium transport in the blood (By similarity). The rank order of affinity is zinc > calcium > magnesium (By similarity).
Binds to the bacterial siderophore enterobactin and inhibits enterobactin-mediated iron uptake of E.coli from ferric transferrin, and may thereby limit the utilization of iron and growth of enteric bacteria such as E.coli .
PMID:6234017
Does not prevent iron uptake by the bacterial siderophore aerobactin PMID:6234017
Biological pathways(1)
Scientific references(3)
Inoue K., Yuasa H.
Molecular Basis for Pharmacokinetics and Pharmacodynamics of Methotrexate in Rheumatoid Arthritis Therapy.
Drug Metabolism and Pharmacokinetics
201429(1):12-19. doi: 10.2133/dmpk.dmpk-13-rv-119
Przekop PR Jr, Tulgan H., Przekop A.A., Glantz M.
SUBJECT AND DRUG INDEXES TO ADVERSE DRUG REACTION BULLETIN.
Adverse Drug Reaction Bulletin
1997185(1):706. doi: 10.1097/00012995-199708000-00002
Muhrez K., Benz-de Bretagne I., Nadal-Desbarats L., Blasco H., Gyan E., Choquet S., Montigny F., Emond P., Barin-Le Guellec C.
Endogenous metabolites that are substrates of organic anion transporter's (OATs) predict methotrexate clearance.
Pharmacology Research
2017 Apr118:121-132. doi: 10.1016/j.phrs.2016.05.021. Epub 2016 May 19
ATC classification(2 codes)
ATC L04AX03
ATC L01BA01
Affected organisms(1)
Humans and other mammals
International brands(17)
Salt forms(1)
Methotrexate sodium(DBSALT000115)
Experimental properties(4)
Protein Data Bank entries(83)
1ao8
1axw
1d1g
1ddr
1dds
1df7
1dhi
1dhj
1dls
1dra
1drb
1dre
1e7w
1mxf
1p33
1ra3
1rb3
1rg7
1rh3
1rx3
1tdr
1u70
1u72
2c7v
2drc
2oip
2qk8
3cd2
3cl9
3dat
3dau
3dfr
3drc
3eig
3ia4
3ix9
3qxt
3qxv
3tq9
4dfr
4gh8
4kn0
4ky8
4l6h
4l8f
4l8w
4p66
4p68
4q0d
4qi9
5hi6
5j7w
5x66
6deb
6ojs
6p9z
6pf7
6pf8
6pf9
6pfa
6pfb
6pfc
6pfd
6pfe
6pff
6pfg
6pfh
6pfi
6smn
6smr
6uy3
6wep
7cca
7dp4
7dp5
7f3y
7rg7
7rga
7tx6
8bwp
8v9r
8xom
9c87
Commercial products(325)
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Show
Chemical identifiers
CAS, UNII, InChI Key and database cross-references
Linked compound data from DrugBank Open Data (CC BY-NC 4.0)
Methotrexate
Additional database identifiers
Drugs Product Database (DPD)
5900
Drugs Product Database (DPD)
6197
ChemSpider
112728
BindingDB
66082
PDB
MTX
ZINC
ZINC000001529323
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12441
GenAtlas
TYMS
GeneCards
TYMS
GenBank Gene Database
X02308
GenBank Protein Database
37479
Guide to Pharmacology
2642
UniProt Accession
TYSY_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:794
GenAtlas
ATIC
GeneCards
ATIC
GenBank Gene Database
U37436
GenBank Protein Database
1263196
UniProt Accession
PUR9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2861
GenAtlas
DHFR
GeneCards
DHFR
GenBank Gene Database
J00140
GenBank Protein Database
182724
Guide to Pharmacology
2603
UniProt Accession
DYR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10937
GeneCards
SLC19A1
Guide to Pharmacology
1014
UniProt Accession
S19A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:30521
GenAtlas
SLC46A1
GeneCards
SLC46A1
GenBank Gene Database
AK054669
GenBank Protein Database
16549261
Guide to Pharmacology
1213
UniProt Accession
PCFT_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2861
GenAtlas
DHFR
GeneCards
DHFR
GenBank Gene Database
J00140
GenBank Protein Database
182724
Guide to Pharmacology
2603
UniProt Accession
DYR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:553
GeneCards
AOX1
GenBank Gene Database
L11005
GenBank Protein Database
438656
Guide to Pharmacology
3186
UniProt Accession
AOXA_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:7436
GenAtlas
MTHFR
GeneCards
MTHFR
GenBank Gene Database
U09806
GenBank Protein Database
6139053
UniProt Accession
MTHR_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8891
GeneCards
PGD
GenBank Gene Database
U30255
GenBank Protein Database
984325
UniProt Accession
6PGD_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3824
GenAtlas
FPGS
GeneCards
FPGS
GenBank Gene Database
M98045
GenBank Protein Database
292029
UniProt Accession
FOLC_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12441
GenAtlas
TYMS
GeneCards
TYMS
GenBank Gene Database
X02308
GenBank Protein Database
37479
Guide to Pharmacology
2642
UniProt Accession
TYSY_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:794
GenAtlas
ATIC
GeneCards
ATIC
GenBank Gene Database
U37436
GenBank Protein Database
1263196
UniProt Accession
PUR9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:4248
GenAtlas
GGH
GeneCards
GGH
GenBank Gene Database
U55206
GenBank Protein Database
2951931
UniProt Accession
GGH_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
UniProt Accession
CBPG_PSES6
HUGO Gene Nomenclature Committee (HGNC)
HGNC:399
GenAtlas
ALB
GeneCards
ALB
GenBank Gene Database
V00494
GenBank Protein Database
28590
UniProt Accession
ALBU_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:54
GenAtlas
ABCC3
GeneCards
ABCC3
GenBank Gene Database
AB010887
GenBank Protein Database
3132270
UniProt Accession
MRP3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:55
GenAtlas
ABCC4
GeneCards
ABCC4
GenBank Gene Database
AF071202
GenBank Protein Database
3335173
Guide to Pharmacology
782
UniProt Accession
MRP4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:51
GenAtlas
ABCC1
GeneCards
ABCC1
GenBank Gene Database
L05628
GenBank Protein Database
1835659
Guide to Pharmacology
779
UniProt Accession
MRP1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10970
GenAtlas
hROAT1
GeneCards
SLC22A6
GenBank Gene Database
AF057039
GenBank Protein Database
3831566
Guide to Pharmacology
1025
UniProt Accession
S22A6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:52
GeneCards
ABCC10
GenBank Gene Database
AY032599
GenBank Protein Database
21103955
UniProt Accession
MRP7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10972
GeneCards
SLC22A8
GenBank Gene Database
AF097491
GenBank Protein Database
4378059
Guide to Pharmacology
1027
UniProt Accession
S22A8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:53
GenAtlas
ABCC2
GeneCards
ABCC2
GenBank Gene Database
U63970
GenBank Protein Database
1764162
Guide to Pharmacology
780
UniProt Accession
MRP2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:40
GenAtlas
ABCB1
GeneCards
ABCB1
GenBank Gene Database
M14758
GenBank Protein Database
307180
Guide to Pharmacology
768
UniProt Accession
MDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10956
GeneCards
SLCO1A2
GenBank Gene Database
U21943
GenBank Protein Database
885978
Guide to Pharmacology
1219
UniProt Accession
SO1A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10922
GenAtlas
SLC16A1
GeneCards
SLC16A1
GenBank Gene Database
L31801
GenBank Protein Database
561722
Guide to Pharmacology
988
UniProt Accession
MOT1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:14639
GeneCards
ABCC11
GenBank Gene Database
AY040219
GenBank Protein Database
15027829
UniProt Accession
MRP8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10961
GeneCards
SLCO1B3
GenBank Gene Database
AJ251506
GenBank Protein Database
9187497
Guide to Pharmacology
1221
UniProt Accession
SO1B3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:18120
GenAtlas
SLC22A11
GeneCards
SLC22A11
GenBank Gene Database
AB026116
GenBank Protein Database
7707622
Guide to Pharmacology
1030
UniProt Accession
S22AB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:13819
GeneCards
SLCO1C1
GenBank Gene Database
AF260704
GenBank Protein Database
7839587
UniProt Accession
SO1C1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10952
GeneCards
SLCO3A1
GenBank Gene Database
AB031050
GenBank Protein Database
6683741
UniProt Accession
SO3A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:74
GenAtlas
ABCG2
GeneCards
ABCG2
GenBank Gene Database
AF103796
GenBank Protein Database
4185796
Guide to Pharmacology
792
UniProt Accession
ABCG2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10971
GeneCards
SLC22A7
GenBank Gene Database
AF097518
GenBank Protein Database
5001689
UniProt Accession
S22A7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:30521
GenAtlas
SLC46A1
GeneCards
SLC46A1
GenBank Gene Database
AK054669
GenBank Protein Database
16549261
Guide to Pharmacology
1213
UniProt Accession
PCFT_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10959
GenAtlas
SLCO1B1
GeneCards
SLCO1B1
GenBank Gene Database
AF060500
GenBank Protein Database
5051630
Guide to Pharmacology
1220
UniProt Accession
SO1B1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:23612
GeneCards
SLCO4C1
GenBank Gene Database
AF401643
GenBank Protein Database
33308060
UniProt Accession
SO4C1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10937
GeneCards
SLC19A1
Guide to Pharmacology
1014
UniProt Accession
S19A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3791
GenAtlas
FOLR1
GeneCards
FOLR1
GenBank Gene Database
M28099
Guide to Pharmacology
3212
UniProt Accession
FOLR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3793
GenAtlas
FOLR2
GeneCards
FOLR2
GenBank Gene Database
X69516
GenBank Protein Database
1655592
UniProt Accession
FOLR2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:10920
GenAtlas
SLC15A1
GeneCards
SLC15A1
GenBank Gene Database
U13173
GenBank Protein Database
773588
Guide to Pharmacology
984
UniProt Accession
S15A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:18761
GenAtlas
SLC36A1
GeneCards
SLC36A1
GenBank Gene Database
AF516142
GenBank Protein Database
31324239
Guide to Pharmacology
1161
UniProt Accession
S36A1_HUMAN
International reference pricing
20 formulations
Reference pricing from DrugBank. Prices are indicative and may not reflect current UK costs.
From $0.66/tablet
To $261.33/g
Apo-Methotrexate 2.5 mg Tablet
$0.66/tablet
Ratio-Methotrexate Sodium 2.5 mg Tablet
$0.66/tablet
Methotrexate 10 mg Tablet
$2.58/tablet
Methotrexate 2.5 mg tablet
$2.71/tablet
Methotrexate Sod.(Unpreserved) 25 mg/ml
$4.56/ml
Source: DrugBank. Used under CC BY-NC 4.0 academic licence for non-commercial purposes.
Patent information
21 active patents, 9 expired
11129833
United States
Approved 28 Sept 2021 · Expires 28 Oct 2035
9y 7m
11771701
United States
Approved 3 Oct 2023 · Expires 29 Oct 2034
8y 7m
9259427
United States
Approved 16 Feb 2016 · Expires 2 Jan 2033
6y 9m
9855215
United States
Approved 2 Jan 2018 · Expires 2 Jan 2033
6y 9m
10231927
United States
Approved 19 Mar 2019 · Expires 2 Jan 2033
6y 9m
The earliest active patent expires October 2026. Generic versions may become available after this date.
Source: DrugBank · CC BY-NC 4.0. Patent data sourced from national patent offices. Expiry dates may not reflect extensions, regulatory exclusivity periods, or legal challenges.
DrugBank citations
If you use DrugBank data in your research, please cite the following publications:
Knox C., Wilson M., Klinger C.M., et al
DrugBank 6.
0: the DrugBank Knowledgebase for 2024
Nucleic Acids Res. 2024 Jan 552(D1):D1265-D1275
Wishart D.S., Feunang Y.D., Guo A.C., et al
DrugBank 5.
0: a major update to the DrugBank database for 2018
Nucleic Acids Res. 2017 Nov 846(D1):D1074-D1082
Show earlier publications
Law V., Knox C., Djoumbou Y., et al
DrugBank 4.
0: shedding new light on drug metabolism
Nucleic Acids Res. 2014 Jan 142(1):D1091-7
Knox C., Law V., Jewison T., et al
DrugBank 3.
0: a comprehensive resource for 'omics' research on drugs
Nucleic Acids Res. 2011 Jan39(Database issue):D1035-41
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a knowledgebase for drugs, drug actions and drug targets.
Nucleic Acids Research
2008 Jan36(Database issue):D901-6
Wishart D.S., Knox C., Guo A.C., et al
DrugBank: a comprehensive resource for in silico drug discovery and exploration.
Nucleic Acids Research
2006 Jan 134(Database issue):D668-72
Source: go.drugbank.comCC BY-NC 4.0
Updated 26 days ago(8 Mar 2026)