NAV

Selpercatinib

Identification

Summary

Selpercatinib is a RET receptor tyrosine kinase inhibitor for the treatment of RET-driven non-small cell lung cancer, medullary thyroid cancer, and thyroid cancer in appropriate patient populations.

Brand Names
Retevmo
Generic Name
Selpercatinib
DrugBank Accession Number
DB15685
Background

Selpercatinib is a kinase inhibitor with enhanced specificity for RET tyrosine kinase receptors (RTKs) over other RTK classes.4,3,7 Enhanced RET (Rearranged during transfection) oncogene expression is a hallmark of many cancers. 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. Selpercatinib (LOXO-292) and pralsetinib (BLU-667) represent the first generation of specific RET RTK inhibitors for the treatment of RET-driven cancers.2,4,3,7

Although selpercatinib is currently still under investigation in clinical trial NCT04211337, it was granted accelerated FDA approval on May 8, 2020, for specific RET-driven cancer indications. It is currently marketed under the brand name RETEVMO™ by Loxo Oncology Inc.7 Selpercatinib is also approved by the European Commission.

Type
Small Molecule
Groups
Approved, Investigational
Structure
3D
Similar Structures
Weight
Average: 525.613
Monoisotopic: 525.248837886
Chemical Formula
C29H31N7O3
Synonyms
  • 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile
  • Selpercatinib
External IDs
  • LOXO 292
  • LOXO-292
  • LY-3527723
  • LY3527723
  • WHO 10967
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Pharmacology

Indication

Selpercatinib is approved to treat:

  • adult with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion.9 In Europe, patients should require systemic therapy following prior treatment with immunotherapy and/or platinum-based chemotherapy.8
  • adults and children 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation who require systemic therapy 9 In Europe, patients should have been previously treated with sorafenib and/or lenvatinib.8
  • adults and children 12 years and older with advanced RET-mutant medullary thyroid cancer (MTC) who require systemic therapy following prior treatment with cabozantinib and/or vandetanib 8
  • adults and children 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate) 9
  • adults with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options 9

Selpercatinib is currently approved for these indications under an accelerated approval scheme and continued approval may be contingent on future confirmatory trials.7

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofLocally advanced solid tumors•••••••••••••••••••••••• •• •• ••••• ••• ••••• •••••••• •••••••• •••••••••• ••••••••••• ••••••••• •••••••• ••• •••••• •••••••••••••••
Treatment ofSolid metastatic tumor•••••••••••••••••••• •••••• ••••••••• •••••••••• ••••••••••• ••••••••• •••••••• ••••••• •• •• ••••• ••• ••••• •••••••• ••••••••••••••
Treatment ofAdvanced ret-fusion thyroid cancer••••••••••••••••••••••• •••••• •••••••••••••••••••• •••••••••••••••••• ••••••• •••••••• ••••••••••••••
Treatment ofAdvanced ret-fusion thyroid cancer•••••••••••••••••••••••• •••••••• •••••••• •••••••••• ••••••••••••••
Treatment ofAdvanced ret-mutant medullary thyroid cancer••••••••••••••••••••••• •••••• ••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Selpercatinib exerts anti-tumour activity in specific cancers through inhibition of mutated forms of RET tyrosine kinases.1,4,7 Due to its increased specificity for RET over other tyrosine kinases, selpercatinib is thought to have an improved safety profile compared to other multi-kinase inhibitors.2 Despite this, selpercatinib treatment is associated with hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, risk of impaired wound healing, and embryo-fetal toxicity; some patients may also exhibit hypersensitivity to selpercatinib.7

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.5,4 Constitutive RET activation is primarily achieved through chromosomal rearrangements producing 5' fusions of dimerizable domains to the 3' RET tyrosine kinase domain, such as KIF5B-RET and CCDC6-RET, resulting in constitutive dimerization and subsequent autophosphorylation.4,2,6 Constitutive activation leads to increased downstream signalling and is associated with tumour invasion, migration, and proliferation.1

Selpercatinib is a direct RET kinase inhibitor, exhibiting IC50 values between 0.92 and 67.8 nM depending on the exact RET genotype.7 Information based on natural as well as induced resistance mutations and molecular modelling suggests that selpercatinib directly inhibits RET autophosphorylation by competing with ATP for binding. Various single amino acid mutations at position 810 inhibit selpercatinib binding without significantly altering ATP binding, potentially leading to treatment failures.3

Selpercatinib is also reported to inhibit other tyrosine kinase receptors, including VEGFR1, VEGFR3, FGFR1, FGFR2, and FGFR3, at clinically relevant concentrations. The significance of these effects is not well studied.7

TargetActionsOrganism
AProto-oncogene tyrosine-protein kinase receptor Ret
inhibitor
Humans
UVascular endothelial growth factor receptor 1
inhibitor
Humans
UVascular endothelial growth factor receptor 3
inhibitor
Humans
UFibroblast growth factor receptor 1
inhibitor
Humans
UFibroblast growth factor receptor 2
inhibitor
Humans
UFibroblast growth factor receptor 3
inhibitor
Humans
Absorption

In patients with locally advanced or metastatic solid tumours receiving 160 mg of selpercatinib twice daily, steady-state was achieved after approximately 7 days, with a Cmax of 2,980 (CV 53%) and AUC0-24h of 51,600 (CV 58%). The absolute bioavailability is between 60 and 82% (mean 73%), and the median tmax is two hours. Food has no apparent effect on the AUC or Cmax of selpercatinib. Patients with hepatic impairment display a concomitant increase in AUC0-INF for mild (7%), moderate (32%), and severe (77%) impairment.7

Volume of distribution

Selpercatinib has an apparent volume of distribution of 191 L; the volume of distribution increases with increasing body weight.7

Protein binding

Selpercatinib displays 97% in vitro protein binding independent of concentration and a blood-plasma concentration ratio of 0.7.7

Metabolism

Selpercatinib is predominantly metabolized in the liver by CYP3A4.7

Route of elimination

Selpercatinib administered as a single 160 mg dose in healthy individuals was primarily recovered in feces (69%, 14% unchanged) and urine (24%, 12% unchanged).7

Half-life

Selpercatinib has a half-life of 32 hours in healthy individuals.7

Clearance

Selpercatinib has an apparent clearance of 6L/h; the clearance increases with increasing body weight.7

Adverse Effects
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Toxicity

Toxicity information regarding selpercatinib is not readily available. Patients experiencing an overdose are at an increased risk of severe adverse effects such as hepatotoxicity, hypertension, prolonged QT interval, and hemorrhaging. Symptomatic and supportive measures are recommended.7

Pathways
Not Available
Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Not Available

Interactions

Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
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interactions in your software
AbametapirThe serum concentration of Selpercatinib can be increased when it is combined with Abametapir.
AbemaciclibThe excretion of Abemaciclib can be decreased when combined with Selpercatinib.
AcalabrutinibThe serum concentration of Selpercatinib can be increased when it is combined with Acalabrutinib.
AcebutololSelpercatinib may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Aceclofenac is combined with Selpercatinib.
Food Interactions
  • Take with or without food. Patients on proton pump inhibitors should take selpercatinib with food.

Products

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International/Other Brands
Retevmo (Loxo Oncology Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
RetevmoCapsule40 mg/1OralEli Lilly and Company2020-05-08Not applicableUS flag
RetevmoCapsule40 mgOralLoxo Oncology Inc2022-01-21Not applicableCanada flag
RetevmoCapsule80 mg/1OralEli Lilly and Company2020-05-08Not applicableUS flag
RetevmoCapsule80 mgOralLoxo Oncology Inc2022-01-21Not applicableCanada flag
RetsevmoCapsule80 mgOralEli Lilly Nederland B.V.2021-04-25Not applicableEU flag

Categories

ATC Codes
L01EX22 — Selpercatinib
Drug Categories
Classification
Not classified
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
CEGM9YBNGD
CAS number
2152628-33-4
InChI Key
XIIOFHFUYBLOLW-UHFFFAOYSA-N
InChI
InChI=1S/C29H31N7O3/c1-29(2,37)18-39-24-9-25(28-21(10-30)13-33-36(28)17-24)20-5-6-26(31-12-20)34-15-22-8-23(16-34)35(22)14-19-4-7-27(38-3)32-11-19/h4-7,9,11-13,17,22-23,37H,8,14-16,18H2,1-3H3
IUPAC Name
6-(2-hydroxy-2-methylpropoxy)-4-(6-{6-[(6-methoxypyridin-3-yl)methyl]-3,6-diazabicyclo[3.1.1]heptan-3-yl}pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile
SMILES
COC1=NC=C(CN2C3CC2CN(C3)C2=CC=C(C=N2)C2=CC(OCC(C)(C)O)=CN3N=CC(C#N)=C23)C=C1

References

Synthesis Reference

Charles Todd Eary, Stacey Spencer, Zack Crane, Katelyn Chando, Sylvie Asselin, Weidong Liu, Mike Welch, Adam Cook, Gabrielle R. Kolakowski, Andrew T. Metcalf, David A. Moreno, Tony P. Tang. "Process for the preparation of 6-(2-hydroxy-2-methylpropoxy)-4-(6-(6-((6-methoxypyridin-3-yl)methyl)-3,6-diazabicyclo[3.1.1]heptan-3-yl)pyridin-3-yl)pyrazolo[1,5-a]pyridine-3-carbonitrile." Patent WO2019075092A1, issued April 18, 2019.

General References
  1. Li AY, McCusker MG, Russo A, Scilla KA, Gittens A, Arensmeyer K, Mehra R, Adamo V, Rolfo C: RET fusions in solid tumors. Cancer Treat Rev. 2019 Dec;81:101911. doi: 10.1016/j.ctrv.2019.101911. Epub 2019 Oct 30. [Article]
  2. Russo A, Lopes AR, McCusker MG, Garrigues SG, Ricciardi GR, Arensmeyer KE, Scilla KA, Mehra R, Rolfo C: New Targets in Lung Cancer (Excluding EGFR, ALK, ROS1). Curr Oncol Rep. 2020 Apr 16;22(5):48. doi: 10.1007/s11912-020-00909-8. [Article]
  3. Solomon BJ, Tan L, Lin JJ, Wong SQ, Hollizeck S, Ebata K, Tuch BB, Yoda S, Gainor JF, Sequist LV, Oxnard GR, Gautschi O, Drilon A, Subbiah V, Khoo C, Zhu EY, Nguyen M, Henry D, Condroski KR, Kolakowski GR, Gomez E, Ballard J, Metcalf AT, Blake JF, Dawson SJ, Blosser W, Stancato LF, Brandhuber BJ, Andrews S, Robinson BG, Rothenberg SM: RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies. J Thorac Oncol. 2020 Apr;15(4):541-549. doi: 10.1016/j.jtho.2020.01.006. Epub 2020 Jan 24. [Article]
  4. Subbiah V, Yang D, Velcheti V, Drilon A, Meric-Bernstam F: State-of-the-Art Strategies for Targeting RET-Dependent Cancers. J Clin Oncol. 2020 Apr 10;38(11):1209-1221. doi: 10.1200/JCO.19.02551. Epub 2020 Feb 21. [Article]
  5. Takahashi M, Ritz J, Cooper GM: Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell. 1985 Sep;42(2):581-8. doi: 10.1016/0092-8674(85)90115-1. [Article]
  6. 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. Mol Cancer. 2014 Jul 21;13:176. doi: 10.1186/1476-4598-13-176. [Article]
  7. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
  8. EMA Approved Drug Products: Retsevmo (selpercatinib) Oral Capsules [Link]
  9. FDA Approved Drug Products: RETEVMO (selpercatinib) capsules, for oral use (September 2022) [Link]
Human Metabolome Database
HMDB0304865
ChemSpider
72379991
BindingDB
296429
RxNav
2370147
ChEMBL
CHEMBL4559134
Wikipedia
Selpercatinib
FDA label
Download (447 KB)

Clinical Trials

Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
PhaseStatusPurposeConditionsCount
3Active Not RecruitingTreatmentMedullary Thyroid Cancer (MTC)1
3Active Not RecruitingTreatmentNon-Small Cell Lung Cancer (NSCLC)1
3RecruitingTreatmentNon-Small Cell Lung Carcinoma1
2Active Not RecruitingTreatmentBreast Cancer / Gastrointestinal Tract Cancer / Non-Small Cell Lung Cancer (NSCLC) / Other Cancers1
2Active Not RecruitingTreatmentEpendymoma, Recurrent / Hematopoietic and Lymphatic System Neoplasm / Recurrent Ewing's Sarcoma / Recurrent Hepatoblastoma / Recurrent Langerhans Cell Histiocytosis / Recurrent Lymphoma / Recurrent Malignant Germ Cell Tumor / Recurrent Malignant Gliomas / Recurrent Malignant Solid Neoplasm / Recurrent Medulloblastoma / Recurrent Neuroblastoma / Recurrent Non-Hodgkin Lymphoma / Recurrent Osteosarcoma / Recurrent Peripheral Primitive Neuroectodermal Tumor / Recurrent Rhabdoid Tumor / Recurrent Rhabdomyosarcoma / Recurrent Soft Tissue Sarcoma / Recurrent WHO Grade 2 Glioma / Refractory Ependymoma / Refractory Ewing Sarcoma / Refractory Hepatoblastoma / Refractory Histiocytic and Dendritic Cell Neoplasm / Refractory Langerhans cell histiocytosis / Refractory Lymphomas / Refractory Malignant Germ Cell Tumor / Refractory Malignant Glioma / Refractory Malignant Solid Neoplasm / Refractory Medulloblastoma / Refractory Neuroblastoma / Refractory Non-Hodgkin's lymphoma / Refractory Osteosarcoma / Refractory Peripheral Primitive Neuroectodermal Tumor / Refractory Rhabdoid Tumor / Refractory Rhabdomyosarcoma / Refractory Soft Tissue Sarcomas / Refractory WHO Grade II Glioma / Wilms' tumor1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral40 mg/1
CapsuleOral40 mg
CapsuleOral80 mg/1
CapsuleOral80 mg
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US10137124No2018-11-272037-10-10US flag
US10172851No2019-01-082037-10-10US flag
US10584124No2020-03-102038-10-10US flag
US10112942No2018-10-302037-10-10US flag
US10786489No2020-09-292038-10-10US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility<1 mg/mLhttps://www.selleckchem.com/msds/MSDS_S8781.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.0299 mg/mLALOGPS
logP3.03ALOGPS
logP3.14Chemaxon
logS-4.2ALOGPS
pKa (Strongest Acidic)14.59Chemaxon
pKa (Strongest Basic)6.28Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count9Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area112.04 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity158.75 m3·mol-1Chemaxon
Polarizability57.3 Å3Chemaxon
Number of Rings6Chemaxon
Bioavailability1Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0000090000-bd4cbd1058626c41b751
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-3020290000-98872a24e81a23e60b96
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0uk9-1001930000-cf06d1240130543a5f0b
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-1002490000-a067289bf76e2e101e78
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0032-2004910000-9efee4790b72487e3189
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-014l-3369420000-4dea6010721520b6f1dd
Chromatographic Properties
Collision Cross Sections (CCS)
Not Available

Targets

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Use our structured and evidence-based datasets to unlock new insights and accelerate drug research.
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Details1. Proto-oncogene tyrosine-protein kinase receptor Ret
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
Inhibition of mutant RET kinase activity is thought to be the main mechanism of action for selpercatinib.
General Function
Transmembrane receptor protein tyrosine kinase activity
Specific Function
Receptor tyrosine-protein kinase involved in numerous cellular mechanisms including cell proliferation, neuronal navigation, cell migration, and cell differentiation upon binding with glial cell de...
Gene Name
RET
Uniprot ID
P07949
Uniprot Name
Proto-oncogene tyrosine-protein kinase receptor Ret
Molecular Weight
124317.465 Da
References
  1. Solomon BJ, Tan L, Lin JJ, Wong SQ, Hollizeck S, Ebata K, Tuch BB, Yoda S, Gainor JF, Sequist LV, Oxnard GR, Gautschi O, Drilon A, Subbiah V, Khoo C, Zhu EY, Nguyen M, Henry D, Condroski KR, Kolakowski GR, Gomez E, Ballard J, Metcalf AT, Blake JF, Dawson SJ, Blosser W, Stancato LF, Brandhuber BJ, Andrews S, Robinson BG, Rothenberg SM: RET Solvent Front Mutations Mediate Acquired Resistance to Selective RET Inhibition in RET-Driven Malignancies. J Thorac Oncol. 2020 Apr;15(4):541-549. doi: 10.1016/j.jtho.2020.01.006. Epub 2020 Jan 24. [Article]
  2. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
  3. LIBRETTO-001: Selpercatinib in RET-altered cancers presentation [Link]
Details2. Vascular endothelial growth factor receptor 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vegf-b-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFA, VEGFB and PGF, and plays an essential role in the development of embryonic vasculature, the regulation of angiogenesis, cell ...
Gene Name
FLT1
Uniprot ID
P17948
Uniprot Name
Vascular endothelial growth factor receptor 1
Molecular Weight
150767.185 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details3. Vascular endothelial growth factor receptor 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vascular endothelial growth factor-activated receptor activity
Specific Function
Tyrosine-protein kinase that acts as a cell-surface receptor for VEGFC and VEGFD, and plays an essential role in adult lymphangiogenesis and in the development of the vascular network and the cardi...
Gene Name
FLT4
Uniprot ID
P35916
Uniprot Name
Vascular endothelial growth factor receptor 3
Molecular Weight
152755.94 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details4. Fibroblast growth factor receptor 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of embryonic development, cell proliferation, differentiation ...
Gene Name
FGFR1
Uniprot ID
P11362
Uniprot Name
Fibroblast growth factor receptor 1
Molecular Weight
91866.935 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details5. Fibroblast growth factor receptor 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosi...
Gene Name
FGFR2
Uniprot ID
P21802
Uniprot Name
Fibroblast growth factor receptor 2
Molecular Weight
92024.29 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details6. Fibroblast growth factor receptor 3
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Protein tyrosine kinase activity
Specific Function
Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation and apoptosis. Plays an...
Gene Name
FGFR3
Uniprot ID
P22607
Uniprot Name
Fibroblast growth factor receptor 3
Molecular Weight
87708.905 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]

Enzymes

Details1. Cytochrome P450 3A4
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details2. Cytochrome P450 2C8
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
CYP2C8 inhibition inferred from metabolism of co-administered repaglinide.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details3. Cytochrome P450 3A Subfamily (Protein Group)
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
CYP3A inhibition inferred from metabolism of co-administered midazolam.
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Components:
NameUniProt ID
Cytochrome P450 3A4P08684
Cytochrome P450 3A43Q9HB55
Cytochrome P450 3A5P20815
Cytochrome P450 3A7P24462
References
  1. Flockhart Table of Drug Interactions [Link]
  2. FDA Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers [Link]
  3. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]

Transporters

Details1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details2. ATP-binding cassette sub-family G member 2
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
High-capacity urate exporter functioning in both renal and extrarenal urate excretion. Plays a role in porphyrin homeostasis as it is able to mediates the export of protoporhyrin IX (PPIX) both fro...
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
ATP-binding cassette sub-family G member 2
Molecular Weight
72313.47 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]
Details3. Multidrug and toxin extrusion protein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monovalent cation:proton antiporter activity
Specific Function
Solute transporter for tetraethylammonium (TEA), 1-methyl-4-phenylpyridinium (MPP), cimetidine, N-methylnicotinamide (NMN), metformin, creatinine, guanidine, procainamide, topotecan, estrone sulfat...
Gene Name
SLC47A1
Uniprot ID
Q96FL8
Uniprot Name
Multidrug and toxin extrusion protein 1
Molecular Weight
61921.585 Da
References
  1. FDA Approved Drug Products: Retevmo (selpercatinib) capsules [Link]

Drug created at May 12, 2020 16:08 / Updated at December 01, 2022 11:30