Encorafenib 50mg capsules
Prescription only
Requires a prescription from a doctor or prescriber
Capsule
50mg
Oral
Encorafenib, also known as <em>BRAFTOVI</em>, is a kinase inhibitor.
Active ingredients:
Encorafenib
1 safety notice
Safety information for pregnancy and breastfeeding
Pregnancy
Grades 3 or 4 dermatologic reactions occurred in 21% of patients treated with BRAFTOVI therapy alone compared to 2% of patients treated with BRAFTOVI in combination with binimetinib.[L12216]
Advise females with reproductive potential of the potential risk to a fetus.
Advise females with reproductive potential of the potential risk to a fetus.
Always consult your doctor or midwife before taking any medicine during pregnancy or while breastfeeding. Source: DrugBank (CC BY-NC 4.0).
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 Encorafenib
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Submit a Yellow Card report to the MHRA
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
The European Medicines Agency (EMA) collects suspected adverse reaction reports from across the EU/EEA through the EudraVigilance system. Search for safety data on this medicine.
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Suspected adverse reactions reported for Encorafenib
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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.
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Braftovi 50mg capsules
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WHO defined daily dose (DDD)
450 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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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
Encorafenib
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)
Encorafenib with binimetinib for unresectable or metastatic BRAF V600 mutation-positive melanoma (TA562)
TA562
Technology appraisal
Updated Feb 2019Encorafenib plus cetuximab for previously treated BRAF V600E mutation-positive metastatic colorectal cancer (TA668)
TA668
Technology appraisal
Updated Jan 2021Melanoma: assessment and management (NG14)
NG14
NICE guideline
Updated Jul 2022Nivolumab with ipilimumab for previously treated metastatic colorectal cancer with high microsatellite instability or mismatch repair deficiency (TA716)
TA716
Technology appraisal
Updated Jul 2021Nivolumab for adjuvant treatment of completely resected melanoma with lymph node involvement or metastatic disease (TA684)
TA684
Technology appraisal
Updated Mar 2021Pembrolizumab for adjuvant treatment of completely resected stage 3 melanoma (TA766)
TA766
Technology appraisal
Updated Feb 2022Nivolumab–relatlimab for untreated unresectable or metastatic melanoma in people 12 years and over (TA950)
TA950
Technology appraisal
Updated Feb 2024Bevacizumab (originator and biosimilars) with fluoropyrimidine-based chemotherapy for metastatic colorectal cancer (TA1136)
TA1136
Technology appraisal
Updated Feb 2026Regorafenib for previously treated metastatic colorectal cancer (TA866)
TA866
Technology appraisal
Updated Feb 2023Trifluridine–tipiracil with bevacizumab for treating metastatic colorectal cancer after 2 systemic treatments (TA1008)
TA1008
Technology appraisal
Updated Sept 2024Colorectal cancer (NG151)
NG151
NICE guideline
Updated Dec 2021Fruquintinib for previously treated metastatic colorectal cancer (TA1079)
TA1079
Technology appraisal
Updated Jul 2025Pembrolizumab for adjuvant treatment of resected stage 2B or 2C melanoma (TA837)
TA837
Technology appraisal
Updated Oct 2022Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
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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
None known
Half-life
3.5 hours
Mechanism
Encorafenib is a kinase inhibitor that targets BRAF V600E, as well as wild-type…
Food interactions
3 warnings
Human targets
10 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
50 mg
The pharmacokinetics of encorafenib were studied in healthy subjects and patients with solid tumors, including advanced and unresectable or metastatic…
Half-life
3.5 hours
The mean (CV%) terminal half-life (t1/2) of encorafenib is 3.5 hours (17%).
[L12216]
[L12216]
Protein binding
86%
Encorafenib is 86% bound to human plasma proteins in vitro.
[L12216]
[L12216]
Volume of distribution
164 L
The blood-to-plasma concentration ratio is 0.58. The geometric mean (CV%) of apparent volume of distribution is 164 L (70%).
[L12216]
[L12216]
Metabolism
83%
Encorafenib is primarily metabolized by CYP3A4 (83%) and to a lesser extent by CYP2C19 (16%) and CYP2D6 (1%).
[L48581]
[L48581]
Elimination
100 mg
Following a single oral dose of 100 mg radiolabeled encorafenib, 47% (5% unchanged) of the administered dose was recovered in the feces and 47% (2% unchanged) was recovered in the urine.
[L12216]…
[L12216]…
Clearance
14 L/h
The apparent clearance is 14 L/h (54%) at day 1, increasing to 32 L/h (59%) at steady-state.
[L12216]
[L12216]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Encorafenib, also known as BRAFTOVI, is a kinase inhibitor. Encorafenib inhibits BRAF gene, which encodes for B-raf protein, which is a proto-oncogene involved in various genetic mutations.[L12216] This protein plays a role in regulating the MAP kinase/ERK signaling pathway, which impacts cell division, differentiation, and secretion. Mutations in this gene, most frequently the V600E mutation, are the most commonly identified cancer-causing mutations in melanoma, and have been isolated in various other cancers as well, including non-Hodgkin lymphoma, colorectal cancer, thyroid carcinoma, non-small cell lung carcinoma, hairy cell leukemia and adenocarcinoma of the lung.[L3344]
On June 27, 2018, the Food and Drug Administration approved encorafenib and [binimetinib] (BRAFTOVI and MEKTOVI, Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.[L12216]
On June 27, 2018, the Food and Drug Administration approved encorafenib and [binimetinib] (BRAFTOVI and MEKTOVI, Array BioPharma Inc.) in combination for patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, as detected by an FDA-approved test.[L12216]
Properties:
solid
Avg. mass: 540.01 Da
DrugBank indication
Encorafenib is indicated in combination with [binimetinib] for the treatment of adult patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation and metastatic non-small cell lung cancer (NSCLC) with a BRAF V600E mutation. It is also indicated in combination with [cetuximab] for the treatment of adult patients with metastatic colorectal cancer with a BRAF V600E mutation.
[L48581]
It is also indicated under accelerated approval in combination with [cetuximab] and mFOLFOX6 ([oxaliplatin], [leucovorin], [fluorouracil]), for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.
[L52470]
[L48581]
It is also indicated under accelerated approval in combination with [cetuximab] and mFOLFOX6 ([oxaliplatin], [leucovorin], [fluorouracil]), for the treatment of patients with metastatic colorectal cancer (mCRC) with a BRAF V600E mutation, as detected by an FDA-approved test.
[L52470]
Also known as(213)
Encorafenib
2.7.11.1
BRAF1
p94
Proto-oncogene B-Raf
RAFB1
v-Raf murine sarcoma viral oncogene homolog B1
B-cell lymphoma 1 protein
Dosage forms(7)
(Oral) — 50 mg
(Oral) — 75 mg
Capsule (Oral) — 50 mg/1
Capsule (Oral) — 50 MG
Capsule (Oral) — 75 mg/1
Capsule (Oral) — 75 mg
Capsule, coated (Oral) — 75 mg
Molecular properties(19)
Drug interactions(1348)
Known interactions with other medications. Always consult a healthcare professional.
Ivabradine
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Ivabradine.
Mirabegron
Unknown severity
The serum concentration of Encorafenib can be increased when it is combined with Mirabegron.
Dofetilide
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Dofetilide.
Anagrelide
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Anagrelide.
Disopyramide
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Disopyramide.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Ibutilide.
Grepafloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Grepafloxacin.
Toremifene
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Toremifene.
Trovafloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Trovafloxacin.
Arsenic trioxide
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Arsenic trioxide.
Sparfloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Sparfloxacin.
Lithium cation
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Lithium cation.
Temafloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Temafloxacin.
Vandetanib
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Vandetanib.
Romidepsin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Romidepsin.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Asenapine.
Artemether
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Artemether.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Glasdegib.
Macimorelin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Macimorelin.
Terodiline
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Terodiline.
Citalopram
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Citalopram.
Clemastine
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Clemastine.
Mifepristone
Unknown severity
The serum concentration of Mifepristone can be decreased when it is combined with Encorafenib.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Cocaine.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Bepridil.
Eliglustat
Moderate
The metabolism of Eliglustat can be decreased when combined with Encorafenib.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Imatinib.
Vemurafenib
Unknown severity
The serum concentration of Encorafenib can be increased when it is combined with Vemurafenib.
Domperidone
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Domperidone.
Paliperidone
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Paliperidone.
Zuclopenthixol
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Zuclopenthixol.
Tetrabenazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Tetrabenazine.
Iloperidone
Moderate
The metabolism of Iloperidone can be decreased when combined with Encorafenib.
Deutetrabenazine
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Deutetrabenazine.
Valproic acid
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Valproic acid.
Leuprolide
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Leuprolide.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Goserelin.
Moxifloxacin
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Moxifloxacin.
Sulfisoxazole
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Sulfisoxazole.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Sulpiride.
Nimodipine
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Nimodipine.
Droperidol
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Droperidol.
Oxaliplatin
Unknown severity
The risk or severity of QTc prolongation can be increased when Oxaliplatin is combined with Encorafenib.
Fluorouracil
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Fluorouracil.
Perflutren
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Perflutren.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Atropine.
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Adenosine.
Gadobenic acid
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Gadobenic acid.
Carbinoxamine
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Carbinoxamine.
Nalidixic acid
Unknown severity
The risk or severity of QTc prolongation can be increased when Encorafenib is combined with Nalidixic acid.
Showing 50 of 1348 interactions
Food & lifestyle interactions
Avoid Grapefruit
Avoid grapefruit products. Grapefruit inhibits CYP3A metabolism, which may increase the serum concentration of encorafenib.
Advice
Exercise caution with St. John's Wort. This herb induces CYP3A metabolism, which may reduce serum levels of encorafenib.
Advice
Take with or without food.
Toxicity & overdose
New primary malignancies, cutaneous and non-cutaneous, have been observed in patients treated with BRAF inhibitors and can occur with encorafenib.
[L12216]
In COLUMBUS, a phase 3 safety and efficacy trial,[L12216] cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6%, and basal cell carcinoma occurred in 1.6% of patients who received BRAFTOVI in combination with binimetinib. The median time to first occurrence of cuSCC/KA was 5.8 months (range 1 to 9 months).
[L12216]
Tumor promotion in BRAF Wild-Type Tumors has been observed with encofarenib use.
[L12216]
Hemorrhage, uveitis, QT interval prolongation are also other adverse events observed while taking this medication.
[L12216]
Encorafenib, when used as a single agent, is associated with an increased risk of certain adverse reactions compared to when BRAFTOVI is used in combination with binimetinib. Grades 3 or 4 dermatologic reactions occurred in 21% of patients treated with BRAFTOVI therapy alone compared to 2% of patients treated with BRAFTOVI in combination with binimetinib.
[L12216]
Advise females with reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose.
[L12216]
Carcinogenicity studies with encorafenib have not been conducted. Encorafenib was not genotoxic in studies evaluating reverse mutations in bacteria, chromosomal aberrations in mammalian cells, or micronuclei in the bone marrow of rats.
[L48581]
No dedicated fertility studies were performed with encorafenib in animals. In a general toxicology study in rats, decreased testes and epididymis weights, tubular degeneration in testes, and oligospermia in epididymides were observed at doses approximately 13 times the human exposure at the 450 mg clinical dose based on AUC.
No effects on reproductive organs were observed in either sex in any of the non-human primate toxicity studies.
[L48581]
Since encorafenib is 86% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with encorafenib.
[L48581]
[L12216]
In COLUMBUS, a phase 3 safety and efficacy trial,[L12216] cutaneous squamous cell carcinoma (cuSCC), including keratoacanthoma (KA), occurred in 2.6%, and basal cell carcinoma occurred in 1.6% of patients who received BRAFTOVI in combination with binimetinib. The median time to first occurrence of cuSCC/KA was 5.8 months (range 1 to 9 months).
[L12216]
Tumor promotion in BRAF Wild-Type Tumors has been observed with encofarenib use.
[L12216]
Hemorrhage, uveitis, QT interval prolongation are also other adverse events observed while taking this medication.
[L12216]
Encorafenib, when used as a single agent, is associated with an increased risk of certain adverse reactions compared to when BRAFTOVI is used in combination with binimetinib. Grades 3 or 4 dermatologic reactions occurred in 21% of patients treated with BRAFTOVI therapy alone compared to 2% of patients treated with BRAFTOVI in combination with binimetinib.
[L12216]
Advise females with reproductive potential of the potential risk to a fetus.
Advise females of reproductive potential to use effective non-hormonal contraception during treatment with BRAFTOVI and for 2 weeks after the final dose.
[L12216]
Carcinogenicity studies with encorafenib have not been conducted. Encorafenib was not genotoxic in studies evaluating reverse mutations in bacteria, chromosomal aberrations in mammalian cells, or micronuclei in the bone marrow of rats.
[L48581]
No dedicated fertility studies were performed with encorafenib in animals. In a general toxicology study in rats, decreased testes and epididymis weights, tubular degeneration in testes, and oligospermia in epididymides were observed at doses approximately 13 times the human exposure at the 450 mg clinical dose based on AUC.
No effects on reproductive organs were observed in either sex in any of the non-human primate toxicity studies.
[L48581]
Since encorafenib is 86% bound to plasma proteins, hemodialysis is likely to be ineffective in the treatment of overdose with encorafenib.
[L48581]
How it works
Mechanism of action
Encorafenib is a kinase inhibitor that targets BRAF V600E, as well as wild-type BRAF and CRAF in in vitro cell-free assays with IC50 values of 0.35, 0.47, and 0.3 nM, respectively. Mutations in the BRAF gene, such as BRAF V600E, can result in constitutively activated BRAF kinases that may stimulate tumor cell growth. Encorafenib was also able to bind to other kinases in vitro including JNK1, JNK2, JNK3, LIMK1, LIMK2, MEK4, and STK36, and reduce ligand binding to these kinases at clinically achievable concentrations (≤0.9 µM).[L48581]
Pharmacodynamics
Encorafenib has a pharmacologic profile that is distinct from that of other clinically active BRAF inhibitors and has shown improved efficacy in the treatment of metastatic melanoma.[L3347][A34311]
Once-daily dosing of single-agent encorafenib has a distinct tolerability profile and shows varying antitumor activity across BRAFi-pretreated and BRAFi-naïve patients with advanced/metastatic stage melanoma [L3347].
Encorafenib inhibited in vitro growth of tumor cell lines expressing BRAF V600 E, D, and K mutations. In mice implanted with tumor cells expressing BRAF V600E, encorafenib induced tumor regressions associated with RAF/MEK/ERK pathway suppression.[L48581]
Encorafenib and binimetinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared with either drug alone, the co-administration of encorafenib and binimetinib resulted in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. Additionally, the combination of encorafenib and binimetinib delayed the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared to either drug alone. In a BRAF V600E mutant NSCLC patient-derived xenograft model in mice, coadministration of encorafenib and binimetinib resulted in greater anti-tumor activity compared to binimetinib alone, with respect to tumor growth inhibition. Increased tumor growth delay after dosing cessation was also observed with the co-administration compared to either drug alone.[L48581]
In the setting of BRAF-mutant CRC, induction of EGFR-mediated MAPK pathway activation has been identified as a mechanism of resistance to BRAF inhibitors. Combinations of a BRAF inhibitor and agents targeting EGFR have been shown to overcome this resistance mechanism in nonclinical models. The co-administration of encorafenib and cetuximab had an anti-tumor effect greater than either drug alone, in a mouse model of colorectal cancer with mutated BRAF V600E.[L48581]
Once-daily dosing of single-agent encorafenib has a distinct tolerability profile and shows varying antitumor activity across BRAFi-pretreated and BRAFi-naïve patients with advanced/metastatic stage melanoma [L3347].
Encorafenib inhibited in vitro growth of tumor cell lines expressing BRAF V600 E, D, and K mutations. In mice implanted with tumor cells expressing BRAF V600E, encorafenib induced tumor regressions associated with RAF/MEK/ERK pathway suppression.[L48581]
Encorafenib and binimetinib target two different kinases in the RAS/RAF/MEK/ERK pathway. Compared with either drug alone, the co-administration of encorafenib and binimetinib resulted in greater anti-proliferative activity in vitro in BRAF mutation-positive cell lines and greater anti-tumor activity with respect to tumor growth inhibition in BRAF V600E mutant human melanoma xenograft studies in mice. Additionally, the combination of encorafenib and binimetinib delayed the emergence of resistance in BRAF V600E mutant human melanoma xenografts in mice compared to either drug alone. In a BRAF V600E mutant NSCLC patient-derived xenograft model in mice, coadministration of encorafenib and binimetinib resulted in greater anti-tumor activity compared to binimetinib alone, with respect to tumor growth inhibition. Increased tumor growth delay after dosing cessation was also observed with the co-administration compared to either drug alone.[L48581]
In the setting of BRAF-mutant CRC, induction of EGFR-mediated MAPK pathway activation has been identified as a mechanism of resistance to BRAF inhibitors. Combinations of a BRAF inhibitor and agents targeting EGFR have been shown to overcome this resistance mechanism in nonclinical models. The co-administration of encorafenib and cetuximab had an anti-tumor effect greater than either drug alone, in a mouse model of colorectal cancer with mutated BRAF V600E.[L48581]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
The pharmacokinetics of encorafenib were studied in healthy subjects and patients with solid tumors, including advanced and unresectable or metastatic cutaneous melanoma harboring a BRAF V600E or V600K mutation, BRAF V600E mutation-positive metastatic CRC. After a single dose, systemic exposure of encorafenib was dose-proportional over the dose range of 50 mg to 700 mg (0.1 to 1.6 times the maximum recommended dose of 450 mg). After once-daily dosing, systemic exposure of encorafenib was less than dose-proportional over the dose range of 50 mg to 800 mg (0.1 to 1.8 times the maximum recommended dose of 450 mg).
Steady-state was reached within 15 days, with exposure being 50% lower compared to Day 1; intersubject variability (CV%) of AUC ranged from 12% to 69%.
[L48581]
After oral administration, the median Tmax of encorafenib is 2 hours. At least 86% of the dose is absorbed.
[L48581]
Following administration of a single dose of encorafenib 100 mg (0.2 times the maximum recommended dose of 450 mg) with a high-fat, high-calorie meal (consisting of approximately 150 calories from protein, 350 calories from carbohydrates, and 500 calories from fat) the mean maximum encorafenib concentration (Cmax) decreased by 36% and there was no effect on AUC.
[L48581]
Steady-state was reached within 15 days, with exposure being 50% lower compared to Day 1; intersubject variability (CV%) of AUC ranged from 12% to 69%.
[L48581]
After oral administration, the median Tmax of encorafenib is 2 hours. At least 86% of the dose is absorbed.
[L48581]
Following administration of a single dose of encorafenib 100 mg (0.2 times the maximum recommended dose of 450 mg) with a high-fat, high-calorie meal (consisting of approximately 150 calories from protein, 350 calories from carbohydrates, and 500 calories from fat) the mean maximum encorafenib concentration (Cmax) decreased by 36% and there was no effect on AUC.
[L48581]
Half-life
The mean (CV%) terminal half-life (t1/2) of encorafenib is 3.5 hours (17%).
[L12216]
[L12216]
Protein binding
Encorafenib is 86% bound to human plasma proteins in vitro.
[L12216]
[L12216]
Volume of distribution
The blood-to-plasma concentration ratio is 0.58. The geometric mean (CV%) of apparent volume of distribution is 164 L (70%).
[L12216]
[L12216]
Metabolism
Encorafenib is primarily metabolized by CYP3A4 (83%) and to a lesser extent by CYP2C19 (16%) and CYP2D6 (1%).
[L48581]
[L48581]
Route of elimination
Following a single oral dose of 100 mg radiolabeled encorafenib, 47% (5% unchanged) of the administered dose was recovered in the feces and 47% (2% unchanged) was recovered in the urine.
[L12216]
[L12216]
Clearance
The apparent clearance is 14 L/h (54%) at day 1, increasing to 32 L/h (59%) at steady-state.
[L12216]
[L12216]
Drug targets(10)
Proteins and enzymes this drug interacts with in the body
Serine/threonine-protein kinase B-raf
BRAF
inhibitor
Specific functionATP binding
Cellular location
Nucleus
General function & pharmacology
Protein kinase involved in the transduction of mitogenic signals from the cell membrane to the nucleus (Probable). Phosphorylates MAP2K1, and thereby activates the MAP kinase signal transduction pathway .
PMID:21441910 PMID:29433126
Phosphorylates PFKFB2 .
PMID:36402789
May play a role in the postsynaptic responses of hippocampal neurons PMID:1508179
PMID:21441910 PMID:29433126
Phosphorylates PFKFB2 .
PMID:36402789
May play a role in the postsynaptic responses of hippocampal neurons PMID:1508179
G1/S-specific cyclin-D1
CCND1
inhibitor
Specific functioncyclin-dependent protein serine/threonine kinase activator activity
Cellular location
Nucleus
General function & pharmacology
Regulatory component of the cyclin D1-CDK4 (DC) complex that phosphorylates and inhibits members of the retinoblastoma (RB) protein family including RB1 and regulates the cell-cycle during G(1)/S transition .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:33854235 PMID:8114739 PMID:8302605
Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:8114739 PMID:8302605
Hypophosphorylates RB1 in early G(1) phase .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:8114739 PMID:8302605
Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:8302605
Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity .
PMID:15241418
Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex .
PMID:9106657
Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner PMID:16569215 PMID:18417529
PMID:1827756 PMID:1833066 PMID:19412162 PMID:33854235 PMID:8114739 PMID:8302605
Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complex and the subsequent transcription of E2F target genes which are responsible for the progression through the G(1) phase .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:8114739 PMID:8302605
Hypophosphorylates RB1 in early G(1) phase .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:8114739 PMID:8302605
Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals .
PMID:1827756 PMID:1833066 PMID:19412162 PMID:8302605
Also a substrate for SMAD3, phosphorylating SMAD3 in a cell-cycle-dependent manner and repressing its transcriptional activity .
PMID:15241418
Component of the ternary complex, cyclin D1/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex .
PMID:9106657
Exhibits transcriptional corepressor activity with INSM1 on the NEUROD1 and INS promoters in a cell cycle-independent manner PMID:16569215 PMID:18417529
RAF proto-oncogene serine/threonine-protein kinase
RAF1
inhibitor
Specific functionadenylate cyclase activator activity
Cellular location
Cytoplasm
General function & pharmacology
Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'.
Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T.
Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing.
Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation
Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T.
Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing.
Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation
Mitogen-activated protein kinase 8
MAPK8
inhibitor
Specific functionATP binding
Cellular location
Cytoplasm
General function & pharmacology
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death. Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway .
PMID:28943315
In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity .
PMID:18307971
Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins .
PMID:21856198
Loss of this interaction abrogates the acetylation required for replication initiation .
PMID:21856198
Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 .
PMID:21364637
In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells.
Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation .
PMID:21095239
Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy .
PMID:18570871
Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH .
PMID:16581800 PMID:17296730 PMID:20027304
Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock .
PMID:22441692
Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity .
PMID:10747973
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 .
PMID:22327296
In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly .
PMID:22966201
Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity .
PMID:27568560
Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome .
PMID:28943315
Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation PMID:34048572
PMID:28943315
In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK8/JNK1. In turn, MAPK8/JNK1 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN, JDP2 and ATF2 and thus regulates AP-1 transcriptional activity .
PMID:18307971
Phosphorylates the replication licensing factor CDT1, inhibiting the interaction between CDT1 and the histone H4 acetylase HBO1 to replication origins .
PMID:21856198
Loss of this interaction abrogates the acetylation required for replication initiation .
PMID:21856198
Promotes stressed cell apoptosis by phosphorylating key regulatory factors including p53/TP53 and Yes-associates protein YAP1 .
PMID:21364637
In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells.
Contributes to the survival of erythroid cells by phosphorylating the antagonist of cell death BAD upon EPO stimulation .
PMID:21095239
Mediates starvation-induced BCL2 phosphorylation, BCL2 dissociation from BECN1, and thus activation of autophagy .
PMID:18570871
Phosphorylates STMN2 and hence regulates microtubule dynamics, controlling neurite elongation in cortical neurons (By similarity). In the developing brain, through its cytoplasmic activity on STMN2, negatively regulates the rate of exit from multipolar stage and of radial migration from the ventricular zone (By similarity). Phosphorylates several other substrates including heat shock factor protein 4 (HSF4), the deacetylase SIRT1, ELK1, or the E3 ligase ITCH .
PMID:16581800 PMID:17296730 PMID:20027304
Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock .
PMID:22441692
Phosphorylates the heat shock transcription factor HSF1, suppressing HSF1-induced transcriptional activity .
PMID:10747973
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity).
Phosphorylates JUND and this phosphorylation is inhibited in the presence of MEN1 .
PMID:22327296
In neurons, phosphorylates SYT4 which captures neuronal dense core vesicles at synapses (By similarity). Phosphorylates EIF4ENIF1/4-ET in response to oxidative stress, promoting P-body assembly .
PMID:22966201
Phosphorylates SIRT6 in response to oxidative stress, stimulating its mono-ADP-ribosyltransferase activity .
PMID:27568560
Phosphorylates NLRP3, promoting assembly of the NLRP3 inflammasome .
PMID:28943315
Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation PMID:34048572
Mitogen-activated protein kinase 9
MAPK9
inhibitor
Specific functionATP binding
Cellular location
Cytoplasm
General function & pharmacology
Serine/threonine-protein kinase involved in various processes such as cell proliferation, differentiation, migration, transformation and programmed cell death .
PMID:10376527 PMID:15805466 PMID:17525747 PMID:19675674 PMID:20595622 PMID:21364637 PMID:22441692 PMID:34048572
Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 .
PMID:10376527 PMID:15805466 PMID:17525747 PMID:19675674 PMID:20595622 PMID:21364637 PMID:22441692 PMID:34048572
In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity .
PMID:10376527
In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 .
PMID:15805466
Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 .
PMID:17525747 PMID:21364637
In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells .
PMID:19290929
Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels .
PMID:19290929
Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption .
PMID:20595622
When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway .
PMID:19675674
Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock .
PMID:22441692
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity).
Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation PMID:34048572
PMID:10376527 PMID:15805466 PMID:17525747 PMID:19675674 PMID:20595622 PMID:21364637 PMID:22441692 PMID:34048572
Extracellular stimuli such as pro-inflammatory cytokines or physical stress stimulate the stress-activated protein kinase/c-Jun N-terminal kinase (SAP/JNK) signaling pathway. In this cascade, two dual specificity kinases MAP2K4/MKK4 and MAP2K7/MKK7 phosphorylate and activate MAPK9/JNK2 .
PMID:10376527 PMID:15805466 PMID:17525747 PMID:19675674 PMID:20595622 PMID:21364637 PMID:22441692 PMID:34048572
In turn, MAPK9/JNK2 phosphorylates a number of transcription factors, primarily components of AP-1 such as JUN and ATF2 and thus regulates AP-1 transcriptional activity .
PMID:10376527
In response to oxidative or ribotoxic stresses, inhibits rRNA synthesis by phosphorylating and inactivating the RNA polymerase 1-specific transcription initiation factor RRN3 .
PMID:15805466
Promotes stressed cell apoptosis by phosphorylating key regulatory factors including TP53 and YAP1 .
PMID:17525747 PMID:21364637
In T-cells, MAPK8 and MAPK9 are required for polarized differentiation of T-helper cells into Th1 cells .
PMID:19290929
Upon T-cell receptor (TCR) stimulation, is activated by CARMA1, BCL10, MAP2K7 and MAP3K7/TAK1 to regulate JUN protein levels .
PMID:19290929
Plays an important role in the osmotic stress-induced epithelial tight-junctions disruption .
PMID:20595622
When activated, promotes beta-catenin/CTNNB1 degradation and inhibits the canonical Wnt signaling pathway .
PMID:19675674
Also participates in neurite growth in spiral ganglion neurons (By similarity). Phosphorylates the CLOCK-BMAL1 heterodimer and plays a role in the regulation of the circadian clock .
PMID:22441692
Phosphorylates POU5F1, which results in the inhibition of POU5F1's transcriptional activity and enhances its proteasomal degradation (By similarity).
Phosphorylates ALKBH5 in response to reactive oxygen species (ROS), promoting ALKBH5 sumoylation and inactivation PMID:34048572
Metabolizing enzymes(10)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP1A2Cytochrome P450 1A2
inhibitor
CYP2B6Cytochrome P450 2B6
inhibitor
inducer
CYP2C8Cytochrome P450 2C8
inhibitor
CYP2C9Cytochrome P450 2C9
inhibitor
inducer
CYP2C19Cytochrome P450 2C19
substrate
CYP2D6Cytochrome P450 2D6
substrate
inhibitor
CYP3A4Cytochrome P450 3A4
substrate
inhibitor
inducer
CYP3A5Cytochrome P450 3A5
inhibitor
CYP3A7Cytochrome P450 3A7
inhibitor
UGT1A1UDP-glucuronosyltransferase 1A1
inhibitor
Transporters(7)
Proteins that transport this drug across cell membranes
ATP-dependent translocase ABCB1
ABCB1
substrate
inhibitor
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 family 22 member 2
SLC22A2
inhibitor
Specific functionacetylcholine transmembrane transporter activity
Cellular location
Basolateral cell membrane
General function & pharmacology
Electrogenic voltage-dependent transporter that mediates the transport of a variety of organic cations such as endogenous bioactive amines, cationic drugs and xenobiotics .
PMID:9260930 PMID:9687576
Functions as a Na(+)-independent, bidirectional uniporter .
PMID:21128598 PMID:9687576
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient .
PMID:15212162 PMID:9260930 PMID:9687576
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow .
PMID:15783073
Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters .
PMID:16581093 PMID:17460754 PMID:9687576
Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system .
PMID:17460754
Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium .
PMID:15817714
Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) .
PMID:12089365 PMID:15212162 PMID:17072098 PMID:24961373 PMID:9260930
Mediates the uptake and efflux of quaternary ammonium compound choline .
PMID:9260930
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine .
PMID:12538837 PMID:21128598
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) .
PMID:11907186
Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) .
PMID:12395288 PMID:16394027
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
PMID:9260930 PMID:9687576
Functions as a Na(+)-independent, bidirectional uniporter .
PMID:21128598 PMID:9687576
Cation cellular uptake or release is driven by the electrochemical potential, i.e. membrane potential and concentration gradient .
PMID:15212162 PMID:9260930 PMID:9687576
However, may also engage electroneutral cation exchange when saturating concentrations of cation substrates are reached (By similarity). Predominantly expressed at the basolateral membrane of hepatocytes and proximal tubules and involved in the uptake and disposition of cationic compounds by hepatic and renal clearance from the blood flow .
PMID:15783073
Implicated in monoamine neurotransmitters uptake such as histamine, dopamine, adrenaline/epinephrine, noradrenaline/norepinephrine, serotonin and tyramine, thereby supporting a physiological role in the central nervous system by regulating interstitial concentrations of neurotransmitters .
PMID:16581093 PMID:17460754 PMID:9687576
Also capable of transporting dopaminergic neuromodulators cyclo(his-pro), salsolinol and N-methyl-salsolinol, thereby involved in the maintenance of dopaminergic cell integrity in the central nervous system .
PMID:17460754
Mediates the bidirectional transport of acetylcholine (ACh) at the apical membrane of ciliated cell in airway epithelium, thereby playing a role in luminal release of ACh from bronchial epithelium .
PMID:15817714
Also transports guanidine and endogenous monoamines such as vitamin B1/thiamine, creatinine and N-1-methylnicotinamide (NMN) .
PMID:12089365 PMID:15212162 PMID:17072098 PMID:24961373 PMID:9260930
Mediates the uptake and efflux of quaternary ammonium compound choline .
PMID:9260930
Mediates the bidirectional transport of polyamine agmatine and the uptake of polyamines putrescine and spermidine .
PMID:12538837 PMID:21128598
Able to transport non-amine endogenous compounds such as prostaglandin E2 (PGE2) and prostaglandin F2-alpha (PGF2-alpha) .
PMID:11907186
Also involved in the uptake of xenobiotic 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP) .
PMID:12395288 PMID:16394027
May contribute to regulate the transport of organic compounds in testis across the blood-testis-barrier (Probable)
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
inhibitor
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 6
SLC22A6
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
Organic anion transporter 3
SLC22A8
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)
Solute carrier organic anion transporter family member 1B1
SLCO1B1
inhibitor
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 1B3
SLCO1B3
inhibitor
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
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
Scientific references(1)
Moschos S.J., Pinnamaneni R.
Targeted therapies in melanoma.
Surgery Oncology Clinical N American
2015 Apr24(2):347-58. doi: 10.1016/j.soc.2014.12.011. Epub 2015 Jan 24
ATC classification(1 code)
ATC L01EC03
Affected organisms(1)
Humans and other mammals
Commercial products(8)
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)
Encorafenib
Additional database identifiers
Drugs Product Database (DPD)
23572
ChemSpider
28536139
BindingDB
221688
ZINC
ZINC000068249103
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1097
GenAtlas
BRAF
GeneCards
BRAF
GenBank Gene Database
M95712
GenBank Protein Database
41387220
Guide to Pharmacology
1943
UniProt Accession
BRAF_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:1582
GenAtlas
CCND1
GeneCards
CCND1
GenBank Gene Database
X59798
GenBank Protein Database
35632
UniProt Accession
CCND1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9829
GenAtlas
RAF1
GeneCards
RAF1
GenBank Gene Database
X03484
GenBank Protein Database
35842
Guide to Pharmacology
2184
UniProt Accession
RAF1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6881
GeneCards
MAPK8
GenBank Gene Database
L26318
GenBank Protein Database
474901
Guide to Pharmacology
1496
UniProt Accession
MK08_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6886
GeneCards
MAPK9
GenBank Gene Database
L31951
GenBank Protein Database
598183
Guide to Pharmacology
1497
UniProt Accession
MK09_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6872
GenAtlas
MAPK10
GeneCards
MAPK10
GenBank Gene Database
U07620
GenBank Protein Database
468151
Guide to Pharmacology
1498
UniProt Accession
MK10_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6613
GeneCards
LIMK1
Guide to Pharmacology
2054
UniProt Accession
LIMK1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6614
GeneCards
LIMK2
Guide to Pharmacology
2055
UniProt Accession
LIMK2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6844
GeneCards
MAP2K4
Guide to Pharmacology
2065
UniProt Accession
MP2K4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:17209
GeneCards
STK36
UniProt Accession
STK36_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2596
GenAtlas
CYP1A2
GeneCards
CYP1A2
GenBank Gene Database
Z00036
Guide to Pharmacology
1319
UniProt Accession
CP1A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2615
GeneCards
CYP2B6
GenBank Gene Database
M29874
GenBank Protein Database
181296
Guide to Pharmacology
1324
UniProt Accession
CP2B6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2622
GenAtlas
CYP2C8
GeneCards
CYP2C8
GenBank Gene Database
M17397
Guide to Pharmacology
1325
UniProt Accession
CP2C8_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2623
GenAtlas
CYP2C9
GeneCards
CYP2C9
GenBank Gene Database
AY341248
Guide to Pharmacology
1326
UniProt Accession
CP2C9_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2621
GeneCards
CYP2C19
GenBank Gene Database
M61854
GenBank Protein Database
181344
Guide to Pharmacology
1328
UniProt Accession
CP2CJ_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2625
GenAtlas
CYP2D6
GeneCards
CYP2D6
GenBank Gene Database
M20403
GenBank Protein Database
181350
Guide to Pharmacology
1329
UniProt Accession
CP2D6_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2637
GenAtlas
CYP3A4
GeneCards
CYP3A4
GenBank Gene Database
M18907
Guide to Pharmacology
1337
UniProt Accession
CP3A4_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2638
GenAtlas
CYP3A5
GeneCards
CYP3A5
GenBank Gene Database
J04813
GenBank Protein Database
181346
Guide to Pharmacology
1338
UniProt Accession
CP3A5_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2640
GeneCards
CYP3A7
GenBank Gene Database
D00408
GenBank Protein Database
220149
UniProt Accession
CP3A7_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:12530
GeneCards
UGT1A1
GenBank Gene Database
M57899
GenBank Protein Database
184473
Guide to Pharmacology
2990
UniProt Accession
UD11_HUMAN
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: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:10966
GeneCards
SLC22A2
GenBank Gene Database
X98333
GenBank Protein Database
2281942
Guide to Pharmacology
1020
UniProt Accession
S22A2_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: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: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: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:10961
GeneCards
SLCO1B3
GenBank Gene Database
AJ251506
GenBank Protein Database
9187497
Guide to Pharmacology
1221
UniProt Accession
SO1B3_HUMAN
Patent information
14 active patents
9474754
United States
Approved 25 Oct 2016 · Expires 5 Aug 2033
7y 4m
9763941
United States
Approved 19 Sept 2017 · Expires 21 Nov 2032
6y 7m
9387208
United States
Approved 12 Jul 2016 · Expires 21 Nov 2032
6y 7m
10258622
United States
Approved 16 Apr 2019 · Expires 21 Nov 2032
6y 7m
9314464
United States
Approved 19 Apr 2016 · Expires 4 Jul 2031
5y 3m
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 about 1 month ago(4 Mar 2026)