1 safety notice
Safety information for pregnancy and breastfeeding
Pregnancy
Pralsetinib administered to rats at 20 mg/kg (roughly 2.5-3.6 times the recommended human exposure) resulted in resorption of litters in pregnant female mice in 92% of pregnancies (82% complete resorption); resorption occurred at doses as low as 5 mg/kg (0.3 times the recommended human exposure).
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
Report a side effect
Submit a Yellow Card report to the MHRA
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.
View Drug Analysis Profile
Suspected adverse reactions reported for Pralsetinib
Browse all iDAP reports
Interactive Drug Analysis Profiles for all medicines
Report a side effect
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.
View EudraVigilance report
Suspected adverse reactions reported for Pralsetinib
About EudraVigilance
Learn about EU pharmacovigilance and safety monitoring
EudraVigilance data is published by the European Medicines Agency (EMA). A suspected adverse reaction is not necessarily caused by the medicine.
1 branded products available
Show details
Therapeutically similar medicines
Show details
Avapritinib 25mg tablets
Tablet
25mg
Same therapeutic group
Avapritinib 50mg tablets
Tablet
50mg
Same therapeutic group
Capivasertib 160mg tablets
Tablet
160mg
Same therapeutic group
Capivasertib 200mg tablets
Tablet
200mg
Same therapeutic group
Quizartinib 17.7mg tablets
Tablet
17.7mg
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.
Clinical guidelines and formulary information
British National Formulary
Pralsetinib
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(4)
Pralsetinib for treating RET fusion-positive advanced non-small-cell lung cancer (TA812)
TA812
Technology appraisal
Updated Aug 2022Selpercatinib for untreated RET fusion-positive advanced non-small-cell lung cancer (TA911)
TA911
Technology appraisal
Updated Jul 2023Dabrafenib plus trametinib for treating BRAF V600 mutation-positive advanced non-small-cell lung cancer (TA898)
TA898
Technology appraisal
Updated Jun 2023Lung cancer: diagnosis and management (NG122)
NG122
NICE guideline
Updated Mar 2024Source: National Institute for Health and Care Excellence (NICE). Contains public sector information licensed under the Open Government Licence v3.0.
Check stock at pharmacies and supply information
Show details
Pharmacy stock checkers
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
Show details
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
Show details
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
6.5 hours
Mechanism
Rearranged during transfection (RET) is a transmembrane receptor tyrosine kinase…
Food interactions
1 warning
Human targets
11 targets
Data: DrugBank · CC BY-NC 4.0
Pharmacokinetics at a glance
Absorption
400 mg
Pralsetinib given at 400 mg once daily resulted in a mean steady-state Cmax of 2830 ng/mL (coefficient of variation, CV, 52.5%)…
Half-life
6.5 hours
Pralsetinib has a plasma elimination half-life of 14.7 ± 6.5 hours following a single dose and 22.2 ± 13.5 hours following multiple doses.
[L15986]
[L15986]
Protein binding
97.1%
Pralsetinib is 97.1% bound to plasma proteins regardless of concentration.
[L15986]
[L15986]
Volume of distribution
228 L
Pralsetinib has a mean apparent volume of distribution of 228 L (CV 75%).
[L15986]
[L15986]
Metabolism
310 mg
Pralsetinib is metabolized in vitro primarily by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2.…
Elimination
73%
Pralsetinib is primarily eliminated through the fecal route (73%, 66% unchanged) with a small amount found in the urine (6%, 4.8%…
Clearance
9.1 L/h
Pralsetinib has a mean apparent steady-state oral clearance of 9.1 L/h (CV 60%).
[L15986]
[L15986]
Pharmacokinetic data: DrugBank · CC BY-NC 4.0
Status:
Approved
Investigational
Small molecule
About this compound
Pralsetinib, similar to the previously approved [selpercatinib], is a kinase inhibitor with enhanced specificity for RET tyrosine kinase receptors (RTKs) over other RTK classes.[A202055][A219751][L15986] Enhanced RET (Rearranged during transfection) oncogene expression is a hallmark of many cancers, including non-small cell lung cancer. Although multikinase inhibitors, including [cabozantinib], [ponatinib], [sorafenib], [sunitinib], and [vandetanib], have shown efficacy in RET-driven cancers, their lack of specificity is generally associated with substantial toxicity.[A202055] Pralsetinib (BLU-667) and [selpercatinib] (LOXO-292) represent the first generation of specific RET RTK inhibitors for the treatment of RET-driven cancers.[A202049][A202055][L15986]
Although a phase 1/2 trial of pralsetinib termed ARROW (NCT03037385) is still ongoing, pralsetinib was granted accelerated FDA approval on September 4, 2020, for the treatment of metastatic RET-fusion positive non-small cell lung cancer. It is currently marketed under the brand name GAVRETO™ by Blueprint Medicines.[L15986]
Although a phase 1/2 trial of pralsetinib termed ARROW (NCT03037385) is still ongoing, pralsetinib was granted accelerated FDA approval on September 4, 2020, for the treatment of metastatic RET-fusion positive non-small cell lung cancer. It is currently marketed under the brand name GAVRETO™ by Blueprint Medicines.[L15986]
Properties:
solid
Avg. mass: 533.61 Da
DrugBank indication
Pralsetinib is indicated for the treatment of metastatic non-small cell lung cancer (NSCLC) in adult patients who are confirmed to possess a rearranged during transfection (RET) gene fusion, as determined by an FDA approved test.
[L15986]
It is also indicated in adult and pediatric patients 12 years of age and older for the treatment of advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and for whom radioactive iodine is not appropriate.
[L47905]
The indication for advanced or metastatic RET fusion-positive thyroid cancer was approved under accelerated approval based on the overall response rate and duration of response, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
[L47905]
[L15986]
It is also indicated in adult and pediatric patients 12 years of age and older for the treatment of advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and for whom radioactive iodine is not appropriate.
[L47905]
The indication for advanced or metastatic RET fusion-positive thyroid cancer was approved under accelerated approval based on the overall response rate and duration of response, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
[L47905]
Also known as(214)
Pralsetinib
2.7.10.1
Cadherin family member 12
CDHF12
CDHR16
Proto-oncogene c-Ret
PTC
2.7.10.1
Dosage forms(3)
(Oral) — 100 mg
Capsule (Oral) — 100 mg
Capsule (Oral) — 100 mg/1
Molecular properties(17)
Drug interactions(887)
Known interactions with other medications. Always consult a healthcare professional.
The serum concentration of Bosutinib can be increased when it is combined with Pralsetinib.
Brentuximab vedotin
Unknown severity
The serum concentration of Brentuximab vedotin can be increased when it is combined with Pralsetinib.
Pravastatin
Moderate
Pralsetinib may decrease the excretion rate of Pravastatin which could result in a higher serum level.
Fluvoxamine
Unknown severity
The serum concentration of Pralsetinib can be increased when it is combined with Fluvoxamine.
Glimepiride
Moderate
Pralsetinib may decrease the excretion rate of Glimepiride which could result in a higher serum level.
Diethylstilbestrol
Moderate
Pralsetinib may decrease the excretion rate of Diethylstilbestrol which could result in a higher serum level.
Isradipine
Unknown severity
The serum concentration of Pralsetinib can be increased when it is combined with Isradipine.
Flucloxacillin
Moderate
Pralsetinib may decrease the excretion rate of Flucloxacillin which could result in a higher serum level.
Indomethacin
Moderate
Pralsetinib may decrease the excretion rate of Indomethacin which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Atenolol which could result in a higher serum level.
Rosiglitazone
Moderate
Pralsetinib may decrease the excretion rate of Rosiglitazone which could result in a higher serum level.
Cerivastatin
Moderate
Pralsetinib may decrease the excretion rate of Cerivastatin which could result in a higher serum level.
Loratadine
Moderate
Pralsetinib may decrease the excretion rate of Loratadine which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Atropine which could result in a higher serum level.
Diclofenac
Moderate
Pralsetinib may decrease the excretion rate of Diclofenac which could result in a higher serum level.
Nicardipine
Unknown severity
The serum concentration of Pralsetinib can be increased when it is combined with Nicardipine.
The metabolism of Losartan can be decreased when combined with Pralsetinib.
Fluorescein
Moderate
Pralsetinib may decrease the excretion rate of Fluorescein which could result in a higher serum level.
Nitrofurantoin
Moderate
Pralsetinib may decrease the excretion rate of Nitrofurantoin which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Naproxen which could result in a higher serum level.
Disulfiram
Moderate
Pralsetinib may decrease the excretion rate of Disulfiram which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Cefaclor which could result in a higher serum level.
Tinidazole
Moderate
Pralsetinib may decrease the excretion rate of Tinidazole which could result in a higher serum level.
Repaglinide
Moderate
Pralsetinib may decrease the excretion rate of Repaglinide which could result in a higher serum level.
Telmisartan
Moderate
Pralsetinib may decrease the excretion rate of Telmisartan which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Ezetimibe which could result in a higher serum level.
Dipyridamole
Moderate
Pralsetinib may decrease the excretion rate of Dipyridamole which could result in a higher serum level.
Sulfamethoxazole
Moderate
Pralsetinib may decrease the excretion rate of Sulfamethoxazole which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Glyburide which could result in a higher serum level.
Felodipine
Moderate
Pralsetinib may decrease the excretion rate of Felodipine which could result in a higher serum level.
Fenofibrate
Moderate
Pralsetinib may decrease the excretion rate of Fenofibrate which could result in a higher serum level.
Nitrendipine
Moderate
Pralsetinib may decrease the excretion rate of Nitrendipine which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Glipizide which could result in a higher serum level.
Rosuvastatin
Moderate
Pralsetinib may decrease the excretion rate of Rosuvastatin which could result in a higher serum level.
Nifedipine
Moderate
Pralsetinib may decrease the excretion rate of Nifedipine which could result in a higher serum level.
Sulfinpyrazone
Moderate
Pralsetinib may decrease the excretion rate of Sulfinpyrazone which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Ofloxacin which could result in a higher serum level.
Budesonide
Moderate
Pralsetinib may decrease the excretion rate of Budesonide which could result in a higher serum level.
Ursodeoxycholic acid
Moderate
Pralsetinib may decrease the excretion rate of Ursodeoxycholic acid which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Glycochenodeoxycholic Acid which could result in a higher serum level.
Cholic Acid
Moderate
Pralsetinib may decrease the excretion rate of Cholic Acid which could result in a higher serum level.
Taurocholic acid
Moderate
Pralsetinib may decrease the excretion rate of Taurocholic acid which could result in a higher serum level.
Prasterone sulfate
Moderate
Pralsetinib may decrease the excretion rate of Prasterone sulfate which could result in a higher serum level.
Pralsetinib may decrease the excretion rate of Indocyanine green acid form which could result in a higher serum level.
Benzbromarone
Moderate
Pralsetinib may decrease the excretion rate of Benzbromarone which could result in a higher serum level.
Pilsicainide
Moderate
Pralsetinib may decrease the excretion rate of Pilsicainide which could result in a higher serum level.
Dihydroergocristine
Moderate
Pralsetinib may decrease the excretion rate of Dihydroergocristine which could result in a higher serum level.
Glycyrrhizic acid
Moderate
Pralsetinib may decrease the excretion rate of Glycyrrhizic acid which could result in a higher serum level.
Belantamab mafodotin
Moderate
Pralsetinib may decrease the excretion rate of Belantamab mafodotin which could result in a higher serum level.
Colchicine
Unknown severity
The serum concentration of Colchicine can be increased when it is combined with Pralsetinib.
Showing 50 of 887 interactions
Food & lifestyle interactions
Empty Stomach
Take on an empty stomach. Food affects the absorption of pralsetinib. Patients should take pralsetinib either at least one hour before or at least two hours after a meal.
Toxicity & overdose
Pralsetinib administered to rats at 20 mg/kg (roughly 2.5-3.6 times the recommended human exposure) resulted in resorption of litters in pregnant female mice in 92% of pregnancies (82% complete resorption); resorption occurred at doses as low as 5 mg/kg (0.3 times the recommended human exposure). Both male and female rats given 10 mg/kg pralsetinib or more had observable degeneration within the testis/ovaries. In 28-day rat and monkey studies, once-daily pralsetinib resulted in histological necrosis at doses 1.1 or more times the recommended human dose and myocardial hemorrhage at doses 2.6 or more times the recommended human dose.
Also, pralsetinib induced hyperphosphatemia (rats only, dose 2.4-3.5 times the recommended human dose) and multi-organ mineralization (dose 0.11 or more times the recommended human dose).
[L15986]
Also, pralsetinib induced hyperphosphatemia (rats only, dose 2.4-3.5 times the recommended human dose) and multi-organ mineralization (dose 0.11 or more times the recommended human dose).
[L15986]
How it works
Mechanism of action
Rearranged during transfection (RET) is a transmembrane receptor tyrosine kinase containing extracellular, transmembrane, and intracellular domains whose activity is required for normal kidney and nervous system development.[A202061][A202055] Constitutive RET activation is achieved through chromosomal rearrangements producing 5' fusions of dimerizable domains to the 3' RET tyrosine kinase domain leading to constitutive dimerization and subsequent autophosphorylation; the most common fusions are KIF5B-RET and CCDC6-RET, although more than 35 genes have been reported to fuse with RET.[A202055][A202049][A202073] Constitutive activation leads to increased downstream signalling and is associated with tumour invasion, migration, and proliferation.[A202046]
Pralsetinib (formerly referred to as BLU-667) was developed through screening more than 10,000 agnostically designed kinase inhibitors followed by extensive chemical modification to improve its properties. Pralsetinib displays in vitro IC50 values for both WT RET as well as several mutant forms, including CCDC6-RET, in the range of 0.3-0.4 nmol/L, and is 100-fold more selective for RET kinase over 96% of 371 kinases tested.[A219751] It is this specific inhibition of RET kinase that is associated with anti-tumour activity and clinical benefit in patients.[A219751][A219756][L15986]
Despite increased selectivity for RET over other kinases, pralsetinib has been reported to inhibit DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1-2 at clinically relevant concentrations. The significance of these findings remains uncertain.[L15986]
Pralsetinib (formerly referred to as BLU-667) was developed through screening more than 10,000 agnostically designed kinase inhibitors followed by extensive chemical modification to improve its properties. Pralsetinib displays in vitro IC50 values for both WT RET as well as several mutant forms, including CCDC6-RET, in the range of 0.3-0.4 nmol/L, and is 100-fold more selective for RET kinase over 96% of 371 kinases tested.[A219751] It is this specific inhibition of RET kinase that is associated with anti-tumour activity and clinical benefit in patients.[A219751][A219756][L15986]
Despite increased selectivity for RET over other kinases, pralsetinib has been reported to inhibit DDR1, TRKC, FLT3, JAK1-2, TRKA, VEGFR2, PDGFRb, and FGFR1-2 at clinically relevant concentrations. The significance of these findings remains uncertain.[L15986]
Pharmacodynamics
Pralsetinib exerts an anti-tumour effect through specific inhibition of the rearranged during transfection (RET) tyrosine kinase, including multiple distinct oncogenic RET fusions, mutated RET kinase domains harbouring gatekeeper mutations, and in RET kinases with a variety of activating single point mutations.[A202049][A202046][A202055][A219746][L15986] Due to pralsetinib's high selectivity for RET over other kinases, both in vitro and in vivo,[A219751] pralsetinib has been described as having a better safety profile compared to previously used multi-kinase inhibitors.[A202049][A202046][A202055][A219746] Despite this, pralsetinib use may increase the risk of hypertension, hemorrhagic events, impaired wound healing, hepatotoxicity, interstitial lung disease/pneumonitis, and embryo-fetal toxicity.[L15986]
Pharmacokinetics
How the body processes this drug — absorption, distribution, metabolism, and elimination
Absorption
Pralsetinib given at 400 mg once daily resulted in a mean steady-state Cmax of 2830 ng/mL (coefficient of variation, CV, 52.5%) and AUC0-24h of 43900 ng\*h/mL (CV 60.2%). The Cmax and AUC of pralsetinib increased inconsistently with increasing doses between 60 and 600 mg once daily, with a median Tmax across this range of between two and four hours. At 400 mg once daily, pralsetinib reached steady-state plasma concentration by three to five days.
[L15986]
Pralsetinib absorption is affected by food.
A single dose of 400 mg given with a high-fat meal (800 to 1000 calories with 50 to 60% of calories coming from fat) increased the mean Cmax by 104% (95% CI 65-153%), mean AUC0-∞ by 122% (95% CI 96-152%), and the median Tmax from four to 8.5 hours.
[L15986]
[L15986]
Pralsetinib absorption is affected by food.
A single dose of 400 mg given with a high-fat meal (800 to 1000 calories with 50 to 60% of calories coming from fat) increased the mean Cmax by 104% (95% CI 65-153%), mean AUC0-∞ by 122% (95% CI 96-152%), and the median Tmax from four to 8.5 hours.
[L15986]
Half-life
Pralsetinib has a plasma elimination half-life of 14.7 ± 6.5 hours following a single dose and 22.2 ± 13.5 hours following multiple doses.
[L15986]
[L15986]
Protein binding
Pralsetinib is 97.1% bound to plasma proteins regardless of concentration.
[L15986]
[L15986]
Volume of distribution
Pralsetinib has a mean apparent volume of distribution of 228 L (CV 75%).
[L15986]
[L15986]
Metabolism
Pralsetinib is metabolized in vitro primarily by CYP3A4 and to a lesser extent by CYP2D6 and CYP1A2. Pralsetinib given as a single oral dose of 310 mg in healthy volunteers led to the detection of metabolites from both oxidation (M453, M531, and M549b) and glucuronidation (M709), although these constituted less than 5% of the detected material.
[L15986]
[L15986]
Route of elimination
Pralsetinib is primarily eliminated through the fecal route (73%, 66% unchanged) with a small amount found in the urine (6%, 4.8% unchanged).
[L15986]
[L15986]
Clearance
Pralsetinib has a mean apparent steady-state oral clearance of 9.1 L/h (CV 60%).
[L15986]
[L15986]
Drug targets(11)
Proteins and enzymes this drug interacts with in the body
Proto-oncogene tyrosine-protein kinase receptor Ret
RET
inhibitor
Specific functionATP binding
Cellular location
Cell membrane
General function & pharmacology
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation in response to glia cell line-derived growth family factors (GDNF, NRTN, ARTN, PSPN and GDF15) .
PMID:20064382 PMID:20616503 PMID:20702524 PMID:21357690 PMID:21454698 PMID:24560924 PMID:28846097 PMID:28846099 PMID:28953886 PMID:31118272
In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation .
PMID:21994944 PMID:23333276 PMID:28846097 PMID:28846099 PMID:28953886
GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways .
PMID:21994944 PMID:23333276 PMID:24560924 PMID:25242331 PMID:28846097 PMID:28846099 PMID:28953886
Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF .
PMID:20616503 PMID:21994944
Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses .
PMID:28846097 PMID:28846099 PMID:28953886
Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner .
PMID:20702524 PMID:21357690
Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage .
PMID:21357690
Triggers the differentiation of rapidly adapting (RA) mechanoreceptors .
PMID:20064382
Involved in the development of the neural crest (By similarity).
Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 PMID:21454698
PMID:20064382 PMID:20616503 PMID:20702524 PMID:21357690 PMID:21454698 PMID:24560924 PMID:28846097 PMID:28846099 PMID:28953886 PMID:31118272
In contrast to most receptor tyrosine kinases, RET requires not only its cognate ligands but also coreceptors, for activation .
PMID:21994944 PMID:23333276 PMID:28846097 PMID:28846099 PMID:28953886
GDNF ligands (GDNF, NRTN, ARTN, PSPN and GDF15) first bind their corresponding GDNFR coreceptors (GFRA1, GFRA2, GFRA3, GFRA4 and GFRAL, respectively), triggering RET autophosphorylation and activation, leading to activation of downstream signaling pathways, including the MAPK- and AKT-signaling pathways .
PMID:21994944 PMID:23333276 PMID:24560924 PMID:25242331 PMID:28846097 PMID:28846099 PMID:28953886
Acts as a dependence receptor via the GDNF-GFRA1 signaling: in the presence of the ligand GDNF in somatotrophs within pituitary, promotes survival and down regulates growth hormone (GH) production, but triggers apoptosis in absence of GDNF .
PMID:20616503 PMID:21994944
Required for the molecular mechanisms orchestration during intestine organogenesis via the ARTN-GFRA3 signaling: involved in the development of enteric nervous system and renal organogenesis during embryonic life, and promotes the formation of Peyer's patch-like structures, a major component of the gut-associated lymphoid tissue (By similarity). Mediates, through interaction with GDF15-receptor GFRAL, GDF15-induced cell-signaling in the brainstem which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses .
PMID:28846097 PMID:28846099 PMID:28953886
Modulates cell adhesion via its cleavage by caspase in sympathetic neurons and mediates cell migration in an integrin (e.g. ITGB1 and ITGB3)-dependent manner .
PMID:20702524 PMID:21357690
Also active in the absence of ligand, triggering apoptosis through a mechanism that requires receptor intracellular caspase cleavage .
PMID:21357690
Triggers the differentiation of rapidly adapting (RA) mechanoreceptors .
PMID:20064382
Involved in the development of the neural crest (By similarity).
Regulates nociceptor survival and size (By similarity). Phosphorylates PTK2/FAK1 PMID:21454698
Epithelial discoidin domain-containing receptor 1
DDR1
inhibitor
Specific functionATP binding
Cellular location
Cell membrane
General function & pharmacology
Tyrosine kinase that functions as a cell surface receptor for fibrillar collagen and regulates cell attachment to the extracellular matrix, remodeling of the extracellular matrix, cell migration, differentiation, survival and cell proliferation. Collagen binding triggers a signaling pathway that involves SRC and leads to the activation of MAP kinases. Regulates remodeling of the extracellular matrix by up-regulation of the matrix metalloproteinases MMP2, MMP7 and MMP9, and thereby facilitates cell migration and wound healing.
Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing.
Also plays a role in tumor cell invasion. Phosphorylates PTPN11
Required for normal blastocyst implantation during pregnancy, for normal mammary gland differentiation and normal lactation. Required for normal ear morphology and normal hearing (By similarity). Promotes smooth muscle cell migration, and thereby contributes to arterial wound healing.
Also plays a role in tumor cell invasion. Phosphorylates PTPN11
NT-3 growth factor receptor
NTRK3
inhibitor
Specific functionATP binding
Cellular location
Membrane
General function & pharmacology
Receptor tyrosine kinase involved in nervous system and probably heart development. Upon binding of its ligand NTF3/neurotrophin-3, NTRK3 autophosphorylates and activates different signaling pathways, including the phosphatidylinositol 3-kinase/AKT and the MAPK pathways, that control cell survival and differentiation
Receptor-type tyrosine-protein kinase FLT3
FLT3
inhibitor
Specific functionATP binding
Cellular location
Membrane
General function & pharmacology
Tyrosine-protein kinase that acts as a cell-surface receptor for the cytokine FLT3LG and regulates differentiation, proliferation and survival of hematopoietic progenitor cells and of dendritic cells. Promotes phosphorylation of SHC1 and AKT1, and activation of the downstream effector MTOR. Promotes activation of RAS signaling and phosphorylation of downstream kinases, including MAPK1/ERK2 and/or MAPK3/ERK1.
Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways
Promotes phosphorylation of FES, FER, PTPN6/SHP, PTPN11/SHP-2, PLCG1, and STAT5A and/or STAT5B. Activation of wild-type FLT3 causes only marginal activation of STAT5A or STAT5B. Mutations that cause constitutive kinase activity promote cell proliferation and resistance to apoptosis via the activation of multiple signaling pathways
Tyrosine-protein kinase JAK1
JAK1
inhibitor
Specific functionATP binding
Cellular location
Endomembrane system
General function & pharmacology
Tyrosine kinase of the non-receptor type, involved in the IFN-alpha/beta/gamma signal pathway .
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
Kinase partner for the interleukin (IL)-2 receptor PMID:11909529 as well as interleukin (IL)-10 receptor .
PMID:12133952
Kinase partner for the type I interferon receptor IFNAR2 .
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins .
PMID:7759950
Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors PMID:16239216 PMID:32750333 PMID:8232552
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
Kinase partner for the interleukin (IL)-2 receptor PMID:11909529 as well as interleukin (IL)-10 receptor .
PMID:12133952
Kinase partner for the type I interferon receptor IFNAR2 .
PMID:16239216 PMID:28111307 PMID:32750333 PMID:7615558 PMID:8232552
In response to interferon-binding to IFNAR1-IFNAR2 heterodimer, phosphorylates and activates its binding partner IFNAR2, creating docking sites for STAT proteins .
PMID:7759950
Directly phosphorylates STAT proteins but also activates STAT signaling through the transactivation of other JAK kinases associated with signaling receptors PMID:16239216 PMID:32750333 PMID:8232552
Metabolizing enzymes(6)
Enzymes involved in drug metabolism — important for understanding drug interactions
Enzyme activity key
substrate
inhibitor
inducer
CYP3A4Cytochrome P450 3A4
substrate
inhibitor
inducer
CYP3A5Cytochrome P450 3A5
inhibitor
inducer
CYP2D6Cytochrome P450 2D6
substrate
CYP1A2Cytochrome P450 1A2
substrate
CYP2C8Cytochrome P450 2C8
inhibitor
inducer
CYP2C9Cytochrome P450 2C9
inhibitor
inducer
Transporters(8)
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
Broad substrate specificity ATP-binding cassette transporter ABCG2
ABCG2
substrate
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 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
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
Multidrug and toxin extrusion protein 1
SLC47A1
inhibitor
Specific functionantiporter activity
Cellular location
Cell membrane
General function & pharmacology
Multidrug efflux pump that functions as a H(+)/organic cation antiporter .
PMID:16330770 PMID:17509534
Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
PMID:16330770 PMID:17509534
Plays a physiological role in the excretion of cationic compounds including endogenous metabolites, drugs, toxins through the kidney and liver, into urine and bile respectively .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
Mediates the efflux of endogenous compounds such as creatinine, vitamin B1/thiamine, agmatine and estrone-3-sulfate .
PMID:16330770 PMID:17495125 PMID:17509534 PMID:17582384 PMID:18305230 PMID:19158817 PMID:21128598 PMID:24961373
May also contribute to regulate the transport of cationic compounds in testis across the blood-testis-barrier (Probable)
Multidrug and toxin extrusion protein 2
SLC47A2
inhibitor
Specific functionantiporter activity
Cellular location
Cell membrane
General function & pharmacology
Multidrug efflux pump that functions as a H(+)/organic cation antiporter. Mediates the efflux of cationic compounds, such as the model cations, tetraethylammonium (TEA) and 1-methyl-4-phenylpyridinium (MPP+), the platinum-based drug oxaliplatin or weak bases that are positively charged at physiological pH, cimetidine, the platinum-based drugs cisplatin and oxaliplatin or the antidiabetic drug metformin. Mediates the efflux of endogenous compounds such as, creatinine, thiamine and estrone-3-sulfate.
Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Plays a physiological role in the excretion of drugs, toxins and endogenous metabolites through the kidney
Bile salt export pump
ABCB11
inhibitor
Specific functionABC-type bile acid transporter activity
Cellular location
Apical cell membrane
General function & pharmacology
Catalyzes the transport of the major hydrophobic bile salts, such as taurine and glycine-conjugated cholic acid across the canalicular membrane of hepatocytes in an ATP-dependent manner, therefore participates in hepatic bile acid homeostasis and consequently to lipid homeostasis through regulation of biliary lipid secretion in a bile salts dependent manner .
PMID:15791618 PMID:16332456 PMID:18985798 PMID:19228692 PMID:20010382 PMID:20398791 PMID:22262466 PMID:24711118 PMID:29507376 PMID:32203132
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts .
PMID:16332456
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion PMID:15901796 PMID:18245269
PMID:15791618 PMID:16332456 PMID:18985798 PMID:19228692 PMID:20010382 PMID:20398791 PMID:22262466 PMID:24711118 PMID:29507376 PMID:32203132
Transports taurine-conjugated bile salts more rapidly than glycine-conjugated bile salts .
PMID:16332456
Also transports non-bile acid compounds, such as pravastatin and fexofenadine in an ATP-dependent manner and may be involved in their biliary excretion PMID:15901796 PMID:18245269
Scientific references(8)
Russo A., Lopes A.R., McCusker M.G., Garrigues S.G., Ricciardi G.R., Arensmeyer K.E., Scilla K.A., Mehra R., Rolfo C.
New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1).
Curr Oncology Reports
2020 Apr 1622(5):48. doi: 10.1007/s11912-020-00909-8
Li A.Y., McCusker M.G., Russo A., Scilla K.A., Gittens A., Arensmeyer K., Mehra R., Adamo V., Rolfo C.
RET fusions in solid tumors.
Cancer Treat Review
2019 Dec81:101911. doi: 10.1016/j.ctrv.2019.101911. Epub 2019 Oct 30
Subbiah V., Yang D., Velcheti V., Drilon A., Meric-Bernstam F.
State-of-the-Art Strategies for Targeting RET-Dependent Cancers.
Journal of Clinical Oncology
2020 Apr 1038(11):1209-1221. doi: 10.1200/JCO.19.02551. Epub 2020 Feb 21
Stinchcombe T.E.
Current management of RET rearranged non-small cell lung cancer.
Therapeutics Advanced Medicine Oncology
2020 Jul 2612:1758835920928634. doi: 10.1177/1758835920928634. eCollection 2020
Subbiah V., Gainor J.F., Rahal R., Brubaker J.D., Kim J.L., Maynard M., Hu W., Cao Q., Sheets M.P., Wilson D., Wilson K.J., DiPietro L., Fleming P., Palmer M., Hu M.I., Wirth L., Brose M.S., Ou S.I., Taylor M., Garralda E., Miller S., Wolf B., Lengauer C., Guzi T., Evans E.K.
Precision Targeted Therapy with BLU-667 for RET-Driven Cancers.
Cancer Discov
2018 Jul8(7):836-849. doi: 10.1158/2159-8290.CD-18-0338. Epub 2018 Apr 15
Takahashi M., Ritz J., Cooper G.M.
Activation of a novel human transforming gene, ret, by DNA rearrangement.
Cell
1985 Sep42(2):581-8. doi: 10.1016/0092-8674(85)90115-1
Qian Y., Chai S., Liang Z., Wang Y., Zhou Y., Xu X., Zhang C., Zhang M., Si J., Huang F., Huang Z., Hong W., Wang K.
KIF5B-RET fusion kinase promotes cell growth by multilevel activation of STAT3 in lung cancer.
Molecular Cancer
2014 Jul 2113:176. doi: 10.1186/1476-4598-13-176
Piotrowska Z., Isozaki H., Lennerz J.K., Gainor J.F., Lennes I.T., Zhu V.W., Marcoux N., Banwait M.K., Digumarthy S.R., Su W., Yoda S., Riley A.K., Nangia V., Lin J.J., Nagy R.J., Lanman R.B., Dias-Santagata D., Mino-Kenudson M., Iafrate A.J., Heist R.S., Shaw A.T., Evans E.K., Clifford C., Ou S.I., Wolf B., Hata A.N., Sequist L.V.
Landscape of Acquired Resistance to Osimertinib in EGFR-Mutant NSCLC and Clinical Validation of Combined EGFR and RET Inhibition with Osimertinib and BLU-667 for Acquired RET Fusion.
Cancer Discov
2018 Dec8(12):1529-1539. doi: 10.1158/2159-8290.CD-18-1022. Epub 2018 Sep 26
ATC classification(1 code)
ATC L01EX23
Affected organisms(1)
Humans and other mammals
Experimental properties(1)
Commercial products(7)
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)
Pralsetinib
Additional database identifiers
Drugs Product Database (DPD)
23611
ChemSpider
75533827
PDB
Q4J
HUGO Gene Nomenclature Committee (HGNC)
HGNC:9967
GenAtlas
RET
GeneCards
RET
GenBank Gene Database
X12949
Guide to Pharmacology
2185
UniProt Accession
RET_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:2730
GenAtlas
DDR1
GeneCards
DDR1
GenBank Gene Database
L20817
GenBank Protein Database
306475
Guide to Pharmacology
1843
UniProt Accession
DDR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8033
GeneCards
NTRK3
Guide to Pharmacology
1819
UniProt Accession
NTRK3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3765
GenAtlas
FLT3
GeneCards
FLT3
GenBank Gene Database
U02687
GenBank Protein Database
409573
Guide to Pharmacology
1807
UniProt Accession
FLT3_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6190
GeneCards
JAK1
Guide to Pharmacology
2047
UniProt Accession
JAK1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6192
GenAtlas
JAK2
GeneCards
JAK2
GenBank Gene Database
AF058925
Guide to Pharmacology
2048
UniProt Accession
JAK2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8031
GenAtlas
NTRK1
GeneCards
NTRK1
GenBank Gene Database
M23102
GenBank Protein Database
339918
Guide to Pharmacology
1817
UniProt Accession
NTRK1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:6307
GenAtlas
KDR
GeneCards
KDR
GenBank Gene Database
AF035121
GenBank Protein Database
2655412
Guide to Pharmacology
1813
UniProt Accession
VGFR2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:8804
GenAtlas
PDGFRB
GeneCards
PDGFRB
GenBank Gene Database
J03278
GenBank Protein Database
189732
Guide to Pharmacology
1804
UniProt Accession
PGFRB_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3688
GenAtlas
FGFR1
GeneCards
FGFR1
GenBank Gene Database
X51803
GenBank Protein Database
31368
Guide to Pharmacology
1808
UniProt Accession
FGFR1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:3689
GenAtlas
FGFR2
GenBank Gene Database
X52832
GenBank Protein Database
31374
Guide to Pharmacology
1809
UniProt Accession
FGFR2_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: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:2596
GenAtlas
CYP1A2
GeneCards
CYP1A2
GenBank Gene Database
Z00036
Guide to Pharmacology
1319
UniProt Accession
CP1A2_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: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: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: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
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:25588
GeneCards
SLC47A1
GenBank Gene Database
AK001709
GenBank Protein Database
7023138
Guide to Pharmacology
1216
UniProt Accession
S47A1_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:26439
GeneCards
SLC47A2
Guide to Pharmacology
1217
UniProt Accession
S47A2_HUMAN
HUGO Gene Nomenclature Committee (HGNC)
HGNC:42
GenAtlas
ABCB11
GeneCards
ABCB11
GenBank Gene Database
AF091582
GenBank Protein Database
3873243
Guide to Pharmacology
778
UniProt Accession
ABCBB_HUMAN
Patent information
4 active patents
11273160
United States
Approved 15 Mar 2022 · Expires 3 Apr 2039
13 years
11872192
United States
Approved 16 Jan 2024 · Expires 3 Apr 2039
13 years
11963958
United States
Approved 23 Apr 2024 · Expires 3 Apr 2039
13 years
10030005
United States
Approved 24 Jul 2018 · Expires 1 Nov 2036
10y 7m
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 30 days ago(4 Mar 2026)