Identification
- Summary
Enasidenib is an isocitrate dehydrogenase-2 inhibitor used to treat relapsed or refractory acute myeloid leukemia with an isocitrate dehydrogenase-2 mutation.
- Brand Names
- Idhifa
- Generic Name
- Enasidenib
- DrugBank Accession Number
- DB13874
- Background
Enasidenib is an orally available treatment for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with specific mutations in the isocitrate dehydrogenase 2 (IDH2) gene, which is a recurrent mutation detected in 12-20% of adult patients with AML 1,2. Patients eligible for this treatment are selected by testing the presence of IDH2 mutations in the blood or bone marrow. This small molecule acts as an allosteric inhibitor of mutant IDH2 enzyme to prevent cell growth, and it also has shown to block several other enzymes that play a role in abnormal cell differentiation. First developed by Agios Pharmaceuticals and licensed to Celgene, enasidenib was approved by U.S. Food and Drug Administration on August 1, 2017.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Enasidenib (DB13874)
- Weight
- Average: 473.383
Monoisotopic: 473.139877173 - Chemical Formula
- C19H17F6N7O
- Synonyms
- 2-Methyl-1-(4-(6-(trifluoromethyl)pyridin-2-yl)-6-(2-(trifluoromethyl)pyridin-4-ylamino)-1,3,5-triazin-2-ylamino)propan-2-ol
- Enasidenib
- External IDs
- AG 221
- AG-221
Pharmacology
- Indication
Enasidenib is indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation as detected by an FDA-approved test.4
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Refractory acute myeloid leukemia •••••••••••• ••••• •••••• Treatment of Refractory acute myeloid leukemia •••••••••••• ••••• •••••• Treatment of Refractory acute myeloid leukemia •••••••••••• ••••• •••••• Treatment of Relapsed acute myeloid leukemia •••••••••••• ••••• •••••• Treatment of Relapsed acute myeloid leukemia •••••••••••• ••••• •••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Inhibition of the mutant IDH2 enzyme by enasidenib led to decreased 2-hydroxyglutarate (2-HG) levels and induced myeloid differentiation in vitro and in vivo in mouse xenograft models of IDH2 mutated AML. In blood samples from patients with AML with mutated IDH2, enasidenib decreased 2-HG levels, reduced blast counts, and increased percentages of mature myeloid cells.4 In a study involving adult patients with relapsed or refractory AML, an overall response rate of 40.3% was achieved in enasidenib therapy, which was associated with cellular differentiation and maturation without evidence of aplasia.2
The potential for QTc prolongation with enasidenib was evaluated in an open-label study in patients with advanced hematologic malignancies with an IDH2 mutation. No large mean changes in the QTc interval (>20 ms) were observed following treatment with enasidenib.4
- Mechanism of action
Enasidenib is a selective inhibitor of IDH2, a mitochondria-localized enzyme involved in diverse cellular processes, including adaptation to hypoxia, histone demethylation and DNA modification 1. Wild-type IDH proteins play a cruicial role in the Krebs/citric acid cycle where it catalyzes the oxidative decarboxylation of isocitrate to α-ketoglutarate. In comparison, mutant forms of IDH2 enzyme mediates a neomorphic activity and catalyze reduction of α-KG to the (R) enantiomer of 2-hydroxyglutarate, which is associated with DNA and histone hypermethylation, altered gene expression and blocked cellular differentiation of hematopoietic progenitor cells 1. Enasidenib primarily targets the mutant IDH2 variants R140Q, R172S, and R172K with higher potency than the wild type enzyme form Label. Inhibition of the enzyme leads to decreased levels of 2-hydroxyglutarate (2-HG) and promotion of proper differentiation and clonal proliferation of cells of the myeloid lineage 2.
Target Actions Organism AIsocitrate dehydrogenase [NADP], mitochondrial inhibitorHumans - Absorption
The peak plasma concentration (Cmax) is 1.4 mcg/mL [coefficient of variation (CV%) 50%] after a single dose of 100 mg, and 13.1 mcg/mL (CV% 45%) at steady state for 100 mg daily. The area under concentration-time curve (AUC) of enasidenib increases in an approximately dose-proportional manner from 50 mg (0.5 times approved recommended dosage) to 450 mg (4.5 times approved recommended dosage) daily dose. Steady-state plasma levels are reached within 29 days of once-daily dosing. Accumulation is approximately 10-fold when administered once daily.4
The absolute bioavailability after a 100 mg oral dose of enasidenib is approximately 57%. After a single oral dose, the median time to Cmax (Tmax) is 4 hours.4
- Volume of distribution
The mean volume of distribution (Vd) of enasidenib is 55.8 L (CV% 29).4
- Protein binding
Human plasma protein binding of enasidenib and its metabolite AGI-16903 are 98.5% and 96.6% respectively in vitro.4
- Metabolism
Metabolism of enasidenib is mediated by multiple cytochrome P450 (CYP) enzymes (e.g.,CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4), and by multiple UDP glucuronosyl transferases (UGTs) (e.g., UGT1A1, UGT1A3, UGT1A4, UGT1A9, UGT2B7, and UGT2B15) in vitro. Further metabolism of the metabolite AGI-16903 is also mediated by multiple enzymes (e.g., CYP1A2, CYP2C19, CYP3A4, UGT1A1, UGT1A3, and UGT1A9) in vitro. Enasidenib accounted for 89% of the radioactivity in circulation and AGI-16903, the N-dealkylated metabolite, represented 10% of the circulating radioactivity.4
- Route of elimination
Eighty-nine percent (89%) of enasidenib is eliminated in feces and 11% in the urine. Excretion of unchanged enasidenib accounts for 34% of the radiolabeled drug in the feces and 0.4% in the urine.4
- Half-life
Enasidenib has a terminal half-life of 7.9 days.4
- Clearance
Enasidenib has a mean total body clearance (CL/F) of 0.70 L/hour (CV% 62.5).4
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Based on animal embryo-fetal toxicity studies, enasidenib can cause fetal harm when administered to a pregnant woman. There are no available data on enasidenib use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. In animal embryo-fetal toxicity studies, oral administration of enasidenib to pregnant rats and rabbits during organogenesis was associated with embryo-fetal mortality and alterations to growth starting at 0.1 times the steady-state clinical exposure based on the AUC at the recommended human dose. Advise pregnant women of the potential risk to a fetus.4
Carcinogenicity studies have not been performed with enasidenib.4
Enasidenib was not mutagenic in an in vitro bacterial reverse mutation (Ames) assay. Enasidenib was not clastogenic in an in vitro human lymphocyte chromosomal aberration assay, or in an in vivo rat bone marrow micronucleus assay.4
Fertility studies in animals have not been conducted with enasidenib. In repeat-dose toxicity studies with twice daily oral administration of enasidenib in rats up to 90 days in duration, changes were reported in male and female reproductive organs including seminiferous tubular degeneration, hypospermia, atrophy of the seminal vesicle and prostate, decreased corpora lutea and increased atretic follicles in the ovaries, and atrophy in the uterus.4
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir The metabolism of Abacavir can be decreased when combined with Enasidenib. Abametapir The serum concentration of Enasidenib can be increased when it is combined with Abametapir. Abatacept The metabolism of Enasidenib can be increased when combined with Abatacept. Abemaciclib The serum concentration of Abemaciclib can be increased when it is combined with Enasidenib. Abiraterone The metabolism of Enasidenib can be decreased when combined with Abiraterone. - Food Interactions
- Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of enasidenib; however, CYP3A4 is one of many enzymes involved in enasidenib metabolism.
- Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce the serum concentration of enasidenib; however, CYP3A4 is one of many enzymes involved in enasidenib metabolism.
- Take at the same time every day.
- Take with a full glass of water.
- Take with or without food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Product Ingredients
Ingredient UNII CAS InChI Key Enasidenib mesylate UF6PC17XAV 1650550-25-6 ORZHZQZYWXEDDL-UHFFFAOYSA-N - Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Idhifa Tablet 50 mg Oral Celgene 2019-02-27 2022-01-14 Canada 
Idhifa Tablet, film coated 100 mg/1 Oral Celgene Corporation 2017-08-01 Not applicable US 
Idhifa Tablet 100 mg Oral Celgene 2019-02-27 2022-01-14 Canada Idhifa Tablet, film coated 50 mg/1 Oral Celgene Corporation 2017-08-01 Not applicable US
Categories
- ATC Codes
- L01XX59 — Enasidenib
- Drug Categories
- Amines
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- BCRP/ABCG2 Inhibitors
- BCRP/ABCG2 Substrates
- Cytochrome P-450 CYP1A2 Inhibitors
- Cytochrome P-450 CYP1A2 Inhibitors (strength unknown)
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP1A2 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2B6 Inducers
- Cytochrome P-450 CYP2B6 Inducers (strength unknown)
- Cytochrome P-450 CYP2B6 Inhibitors
- Cytochrome P-450 CYP2B6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2B6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C19 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C8 Inhibitors
- Cytochrome P-450 CYP2C8 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C8 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2C9 Inhibitors
- Cytochrome P-450 CYP2C9 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2C9 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP2D6 Inhibitors
- Cytochrome P-450 CYP2D6 Inhibitors (strength unknown)
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 CYP2D6 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A Inhibitors
- Cytochrome P-450 CYP3A Substrates
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 CYP3A4 Inhibitors
- Cytochrome P-450 CYP3A4 Inhibitors (strength unknown)
- Cytochrome P-450 CYP3A4 Substrates
- Cytochrome P-450 CYP3A4 Substrates with a Narrow Therapeutic Index
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Isocitrate Dehydrogenase 2 Inhibitor
- Isocitrate dehydrogenase-2 (IDH2) Inhibitors
- Narrow Therapeutic Index Drugs
- OAT1/SLC22A6 inhibitors
- OAT3/SLC22A8 Inhibitors
- OATP1B1/SLCO1B1 Inhibitors
- OATP1B3 inhibitors
- OCT2 Inhibitors
- P-glycoprotein inhibitors
- P-glycoprotein substrates
- P-glycoprotein substrates with a Narrow Therapeutic Index
- Pyridines
- UGT1A1 Inhibitors
- UGT1A1 Substrates
- UGT1A1 Substrates with a Narrow Therapeutic Index
- UGT1A3 substrates
- UGT1A3 Substrates with a Narrow Therapeutic Index
- UGT1A4 substrates
- UGT1A9 Substrates
- UGT1A9 Substrates with a Narrow Therapeutic Index
- UGT2B7 substrates
- UGT2B7 Substrates with a Narrow Therapeutic Index
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as 1,3,5-triazine-2,4-diamines. These are aromatic compounds containing a 1,3,5-triazine ring which is 2,4-disusbtituted wit amine groups.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Triazines
- Sub Class
- Aminotriazines
- Direct Parent
- 1,3,5-triazine-2,4-diamines
- Alternative Parents
- N-aliphatic s-triazines / Aminopyridines and derivatives / 1,3,5-triazines / Tertiary alcohols / Heteroaromatic compounds / Azacyclic compounds / Organofluorides / Hydrocarbon derivatives / Amines / Alkyl fluorides
- Substituents
- 1,3,5-triazine / 2,4-diamine-s-triazine / Alcohol / Alkyl fluoride / Alkyl halide / Amine / Aminopyridine / Aromatic heteromonocyclic compound / Azacycle / Heteroaromatic compound
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 3T1SS4E7AG
- CAS number
- 1446502-11-9
- InChI Key
- DYLUUSLLRIQKOE-UHFFFAOYSA-N
- InChI
- InChI=1S/C19H17F6N7O/c1-17(2,33)9-27-15-30-14(11-4-3-5-12(29-11)18(20,21)22)31-16(32-15)28-10-6-7-26-13(8-10)19(23,24)25/h3-8,33H,9H2,1-2H3,(H2,26,27,28,30,31,32)
- IUPAC Name
- 2-methyl-1-({4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl}amino)propan-2-ol
- SMILES
- CC(C)(O)CNC1=NC(=NC(NC2=CC(=NC=C2)C(F)(F)F)=N1)C1=NC(=CC=C1)C(F)(F)F
References
- General References
- Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R: Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017 Feb;31(2):272-281. doi: 10.1038/leu.2016.275. Epub 2016 Oct 10. [Article]
- Stein EM, DiNardo CD, Pollyea DA, Fathi AT, Roboz GJ, Altman JK, Stone RM, DeAngelo DJ, Levine RL, Flinn IW, Kantarjian HM, Collins R, Patel MR, Frankel AE, Stein A, Sekeres MA, Swords RT, Medeiros BC, Willekens C, Vyas P, Tosolini A, Xu Q, Knight RD, Yen KE, Agresta S, de Botton S, Tallman MS: Enasidenib in mutant-IDH2 relapsed or refractory acute myeloid leukemia. Blood. 2017 Jun 6. pii: blood-2017-04-779405. doi: 10.1182/blood-2017-04-779405. [Article]
- Amatangelo MD, Quek L, Shih A, Stein EM, Roshal M, David MD, Marteyn B, Rahnamay Farnoud N, de Botton S, Bernard OA, Wu B, Yen KE, Tallman MS, Papaemmanuil E, Penard-Lacronique V, Thakurta A, Vyas P, Levine RL: Enasidenib induces acute myeloid leukemia cell differentiation to promote clinical response. Blood. 2017 Jun 6. pii: blood-2017-04-779447. doi: 10.1182/blood-2017-04-779447. [Article]
- FDA Approved Drug Products: IDHIFA® (enasidenib) tablets, for oral use (Feb 2024) [Link]
- External Links
- Human Metabolome Database
- HMDB0251786
- PubChem Compound
- 89683805
- PubChem Substance
- 347829326
- ChemSpider
- 38772329
- BindingDB
- 50503251
- 1940332
- ChEBI
- 145374
- ChEMBL
- CHEMBL3989908
- ZINC
- ZINC000222731806
- PDBe Ligand
- 69Q
- Wikipedia
- Enasidenib
- PDB Entries
- 5i96
- FDA label
- Download (420 KB)
- MSDS
- Download (27 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Isocitrate Dehydrogenase / Myeloid Leukemias 1 3 Recruiting Treatment Acute Myeloid Leukemia / Myelodysplastic Syndrome With Excess Blasts-2 (MDS-EB-2) 1 2 Active Not Recruiting Treatment Acute Myeloid Leukemia / Chronic Myelomonocytic Leukemia / IDH2 Gene Mutation / IDH2 R140 / IDH2 R172 / Myelodysplastic Syndrome 1 2 Active Not Recruiting Treatment Recurrent Acute Myeloid Leukemia 1 2 Completed Treatment Accelerated/Blast-phase Myeloproliferative Neoplasm / Chronic Phase Myelofibrosis / IDH2 Mutation 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet Oral 100 mg Tablet Oral 50 mg Tablet, film coated Oral 100 mg/1 Tablet, film coated Oral 50 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US9512107 No 2016-12-06 2033-01-07 US US9732062 No 2017-08-15 2034-09-16 US US9738625 No 2017-08-22 2034-08-01 US US10093654 No 2018-10-09 2034-08-01 US US10294215 No 2019-05-21 2033-01-07 US US10610125 No 2020-04-07 2030-06-21 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0366 mg/mL ALOGPS logP 4.25 ALOGPS logP 4.59 Chemaxon logS -4.1 ALOGPS pKa (Strongest Acidic) 11.37 Chemaxon pKa (Strongest Basic) 3.82 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 8 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 108.74 Å2 Chemaxon Rotatable Bond Count 8 Chemaxon Refractivity 118.37 m3·mol-1 Chemaxon Polarizability 41.41 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-a730cd99e7d197cc1d91 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-00di-0000900000-37b4ee3e6001e3c62dfa Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0kmi-0000900000-298cf0f892926f13cbd1 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0229-0509700000-f985ff1fbfb3b5201cbb Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-052b-0009200000-e5f8dea4492d1e92e63c Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-07br-4819000000-1c5866e957f7fa3b8ba9 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 197.61714 predictedDeepCCS 1.0 (2019) [M+H]+ 200.01271 predictedDeepCCS 1.0 (2019) [M+Na]+ 205.95427 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Nad binding
- Specific Function
- Plays a role in intermediary metabolism and energy production. It may tightly associate or interact with the pyruvate dehydrogenase complex.
- Gene Name
- IDH2
- Uniprot ID
- P48735
- Uniprot Name
- Isocitrate dehydrogenase [NADP], mitochondrial
- Molecular Weight
- 50908.915 Da
References
- Medeiros BC, Fathi AT, DiNardo CD, Pollyea DA, Chan SM, Swords R: Isocitrate dehydrogenase mutations in myeloid malignancies. Leukemia. 2017 Feb;31(2):272-281. doi: 10.1038/leu.2016.275. Epub 2016 Oct 10. [Article]
- FDA Approved Drug Products: IDHIFA® (enasidenib) tablets, for oral use (Feb 2024) [Link]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- The FDA label states these data are supported by in vitro studies.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- 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
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Enasidenib FDA label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- Curator comments
- Also inhibited by metabolite AGI-16903
- 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
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Enasidenib FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Also inhibited by metabolite AGI-16903
- 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
- Enasidenib FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Also inhibited by metabolite AGI-16903
- 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
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Enasidenib FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Also inhibited by metabolite AGI-16903. Enasidenib has been shown to act as an in vitro inhibitor of CY2C19. No current in vivo studies are available.
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Also inhibited by metabolite AGI-16903
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitorInducer
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Protein homodimerization activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A4
- Uniprot ID
- P22310
- Uniprot Name
- UDP-glucuronosyltransferase 1-4
- Molecular Weight
- 60024.535 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols. Isoform 2 lacks trans...
- Gene Name
- UGT1A9
- Uniprot ID
- O60656
- Uniprot Name
- UDP-glucuronosyltransferase 1-9
- Molecular Weight
- 59940.495 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds.Its unique specificity for 3,4-catechol estrogens and estriol su...
- Gene Name
- UGT2B7
- Uniprot ID
- P16662
- Uniprot Name
- UDP-glucuronosyltransferase 2B7
- Molecular Weight
- 60694.12 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Glucuronosyltransferase activity
- Specific Function
- UDPGTs are of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isozyme displays activity toward several classes of xeno...
- Gene Name
- UGT2B15
- Uniprot ID
- P54855
- Uniprot Name
- UDP-glucuronosyltransferase 2B15
- Molecular Weight
- 61035.815 Da
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Binder
- General Function
- Toxic substance binding
- Specific Function
- Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
- Gene Name
- ALB
- Uniprot ID
- P02768
- Uniprot Name
- Serum albumin
- Molecular Weight
- 69365.94 Da
References
- Saber Abdelhameed A, Bakheit AH, Hassan ES, Alanazi AM, Naglah AM, AlRabiah H: Spectroscopic and computational investigation of the interaction between the new anticancer agent enasidenib and human serum albumin. Spectrochim Acta A Mol Biomol Spectrosc. 2022 Apr 5;270:120790. doi: 10.1016/j.saa.2021.120790. Epub 2021 Dec 22. [Article]
Transporters
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- Metabolite of enasidenib, AGI-16903 is a substrate of MDR1/P-gp while enasidenib is an inhibitor of MDR1/P-gp.
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- Curator comments
- AGI-16903 is a substrate and inhibitor of BCRP while enasidenib is an inhibitor of BCRP.
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibited by both enasidenib and AGI-16903
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
- Gene Name
- SLC22A6
- Uniprot ID
- Q4U2R8
- Uniprot Name
- Solute carrier family 22 member 6
- Molecular Weight
- 61815.78 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibited by both enasidenib and AGI-16903
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as pravastatin, taurocholate, methotrexate, dehydroepiandrosterone sulfate, 17-beta-glucuronosyl estradiol, estrone sulfate, prostagland...
- Gene Name
- SLCO1B1
- Uniprot ID
- Q9Y6L6
- Uniprot Name
- Solute carrier organic anion transporter family member 1B1
- Molecular Weight
- 76447.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibited by both enasidenib and AGI-16903
- General Function
- Quaternary ammonium group transmembrane transporter activity
- Specific Function
- Mediates tubular uptake of organic compounds from circulation. Mediates the influx of agmatine, dopamine, noradrenaline (norepinephrine), serotonin, choline, famotidine, ranitidine, histamin, creat...
- Gene Name
- SLC22A2
- Uniprot ID
- O15244
- Uniprot Name
- Solute carrier family 22 member 2
- Molecular Weight
- 62579.99 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates the Na(+)-independent uptake of organic anions such as 17-beta-glucuronosyl estradiol, taurocholate, triiodothyronine (T3), leukotriene C4, dehydroepiandrosterone sulfate (DHEAS), methotre...
- Gene Name
- SLCO1B3
- Uniprot ID
- Q9NPD5
- Uniprot Name
- Solute carrier organic anion transporter family member 1B3
- Molecular Weight
- 77402.175 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inhibitor
- Curator comments
- Inhibited by AGI-16903
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
- Gene Name
- SLC22A8
- Uniprot ID
- Q8TCC7
- Uniprot Name
- Solute carrier family 22 member 8
- Molecular Weight
- 59855.585 Da
Drug created at August 02, 2017 14:49 / Updated at February 10, 2024 11:21