Enasidenib

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
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

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofRefractory acute myeloid leukemia•••••••••••••••••••••••
Treatment ofRefractory acute myeloid leukemia•••••••••••••••••••••••
Treatment ofRefractory acute myeloid leukemia•••••••••••••••••••••••
Treatment ofRelapsed acute myeloid leukemia•••••••••••••••••••••••
Treatment ofRelapsed acute myeloid leukemia•••••••••••••••••••••••
Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
AIsocitrate dehydrogenase [NADP], mitochondrial
inhibitor
Humans
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
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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
Not Available

Interactions

Drug Interactions
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
AbacavirThe metabolism of Abacavir can be decreased when combined with Enasidenib.
AbametapirThe serum concentration of Enasidenib can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Enasidenib can be increased when combined with Abatacept.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Enasidenib.
AbirateroneThe 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

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Product Ingredients
IngredientUNIICASInChI Key
Enasidenib mesylateUF6PC17XAV1650550-25-6ORZHZQZYWXEDDL-UHFFFAOYSA-N
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
IdhifaTablet, film coated100 mg/1OralCelgene Corporation2017-08-01Not applicableUS flag
IdhifaTablet100 mgOralCelgene2019-02-272022-01-14Canada flag
IdhifaTablet, film coated50 mg/1OralCelgene Corporation2017-08-01Not applicableUS flag
IdhifaTablet50 mgOralCelgene2019-02-272022-01-14Canada flag

Categories

ATC Codes
L01XX59 — Enasidenib
Drug Categories
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
  1. 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]
  2. 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]
  3. 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]
  4. FDA Approved Drug Products: IDHIFA® (enasidenib) tablets, for oral use (Feb 2024) [Link]
Human Metabolome Database
HMDB0251786
PubChem Compound
89683805
PubChem Substance
347829326
ChemSpider
38772329
BindingDB
50503251
RxNav
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

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
FormRouteStrength
TabletOral100 mg
TabletOral50 mg
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US9512107No2016-12-062033-01-07US flag
US9732062No2017-08-152034-09-16US flag
US9738625No2017-08-222034-08-01US flag
US10093654No2018-10-092034-08-01US flag
US10294215No2019-05-212033-01-07US flag
US10610125No2020-04-072030-06-21US flag

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0366 mg/mLALOGPS
logP4.25ALOGPS
logP4.59Chemaxon
logS-4.1ALOGPS
pKa (Strongest Acidic)11.37Chemaxon
pKa (Strongest Basic)3.82Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count8Chemaxon
Hydrogen Donor Count3Chemaxon
Polar Surface Area108.74 Å2Chemaxon
Rotatable Bond Count8Chemaxon
Refractivity118.37 m3·mol-1Chemaxon
Polarizability41.41 Å3Chemaxon
Number of Rings3Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
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/MSsplash10-00di-0000900000-a730cd99e7d197cc1d91
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00di-0000900000-37b4ee3e6001e3c62dfa
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0kmi-0000900000-298cf0f892926f13cbd1
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0229-0509700000-f985ff1fbfb3b5201cbb
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-052b-0009200000-e5f8dea4492d1e92e63c
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-07br-4819000000-1c5866e957f7fa3b8ba9
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-197.61714
predicted
DeepCCS 1.0 (2019)
[M+H]+200.01271
predicted
DeepCCS 1.0 (2019)
[M+Na]+205.95427
predicted
DeepCCS 1.0 (2019)

Targets

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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
  1. 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]
  2. FDA Approved Drug Products: IDHIFA® (enasidenib) tablets, for oral use (Feb 2024) [Link]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Enasidenib FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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
  1. Enasidenib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Enasidenib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Enasidenib FDA Label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
  1. Dugan J, Pollyea D: Enasidenib for the treatment of acute myeloid leukemia. Expert Rev Clin Pharmacol. 2018 Aug;11(8):755-760. doi: 10.1080/17512433.2018.1477585. Epub 2018 Jul 24. [Article]
  2. Enasidenib FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Substrate
Inhibitor
Inducer
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
Substrate
Inhibitor
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
  1. 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
Substrate
Inhibitor
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
Substrate
Inhibitor
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