Identification

Name
Enasidenib
Accession Number
DB13874
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
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
External IDs
AG 221 / AG-221
Product Ingredients
IngredientUNIICASInChI Key
Enasidenib mesylateUF6PC17XAV1650550-25-6ORZHZQZYWXEDDL-UHFFFAOYSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IdhifaTablet, film coated50 mg/1OralCelgene2017-08-01Not applicableUs
IdhifaTablet, film coated100 mg/1OralCelgene2017-08-01Not applicableUs
Categories
UNII
3T1SS4E7AG
CAS number
1446502-11-9
Weight
Average: 473.383
Monoisotopic: 473.139877173
Chemical Formula
C19H17F6N7O
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

Pharmacology

Indication

Indicated for the treatment of adult patients with relapsed or refractory acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation.

Structured Indications
Not Available
Pharmacodynamics

In a study involving adult patients with relapsed or refractory AML, overall response rate of 40.3% was achieved in enasidenib therapy which was associated with cellular differentiation and maturation, typically without evidence of aplasia [2]. Enasidenib is not shown to cause QTc prolongation.

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 [FDA 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
Human
Absorption

Following a single oral dose of 100mg enasidenib, the peak plasma concentration of 1.3 mcg/mL is reached at 4 hours after ingestion. The absolute bioavailability is aproximately 57% and the steady-state plasma levels are reached within 29 days of once-daily dosing [FDA Label].

Volume of distribution

The mean volume of distribution is 55.8L [FDA Label].

Protein binding

In vitro, human plasma protein binding of enasidenib is 98.5% and 96.6% for its metabolite AGI-16903. Both the parent drug and its main metabolite are not reported to be substrates of MRP2, OAT1, OAT3, OATP1B1, OATP1B3, and OCT2. AGI-16903 is a substrate for both P-glycoprotein and BCRP [FDA Label].

Metabolism

Enasidenib undergoes N-dealkylation mediated by multiple CYP (CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and UGT (UGT1A1, UGT1A3, UGT1A4, UGT1A9, UGT2B7, and UGT2B15) enzymes to form AGI-16903, as suggested by in vitro studies. AGI-16903 can be further metabolized by CYP1A2, CYP2C19, CYP3A4, UGT1A1, UGT1A3, and UGT1A9. The parent drug accounts for 89% of total detectable drug in the circulation, while AGI-16903 represents 10% of circulating total drug [FDA Label].

Route of elimination

Elimination of enasidenib involves 89% of fecal excretion and 11% of renal excretion. Unchanged drug accounts for 34% and 0.4% of the total drug detected in the feces and urine, respectively [FDA Label].

Half life

Enasidenib has a terminal half-life of 137 hours [FDA Label].

Clearance

Enasidenib displays a mean total body clearance (CL/F) of 0.74 L/hour [FDA Label].

Toxicity

Enasidenib is not clastogenic or mutagenic in vitro. In vitro repeat-dose toxicity studies, enasidenib treatment induced changes in male and female reproductive systems 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 [FDA Label].

Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
AbirateroneThe serum concentration of Enasidenib can be increased when it is combined with Abiraterone.Approved
AfatinibThe serum concentration of Afatinib can be increased when it is combined with Enasidenib.Approved
AmiodaroneThe metabolism of Enasidenib can be decreased when combined with Amiodarone.Approved, Investigational
AmodiaquineThe serum concentration of Amodiaquine can be increased when it is combined with Enasidenib.Approved, Investigational
AprepitantThe serum concentration of Enasidenib can be increased when it is combined with Aprepitant.Approved, Investigational
AripiprazoleThe serum concentration of Aripiprazole can be decreased when it is combined with Enasidenib.Approved, Investigational
ArmodafinilThe metabolism of Enasidenib can be decreased when combined with Armodafinil.Approved, Investigational
ArtemetherThe metabolism of Enasidenib can be decreased when combined with Artemether.Approved
AtazanavirThe metabolism of Enasidenib can be decreased when combined with Atazanavir.Approved, Investigational
AtomoxetineThe metabolism of Enasidenib can be decreased when combined with Atomoxetine.Approved
AtorvastatinThe risk or severity of adverse effects can be increased when Enasidenib is combined with Atorvastatin.Approved
AzithromycinThe metabolism of Enasidenib can be decreased when combined with Azithromycin.Approved
BetaxololThe metabolism of Enasidenib can be decreased when combined with Betaxolol.Approved
BoceprevirThe metabolism of Enasidenib can be decreased when combined with Boceprevir.Approved, Withdrawn
BortezomibThe metabolism of Enasidenib can be decreased when combined with Bortezomib.Approved, Investigational
BosentanThe serum concentration of Enasidenib can be decreased when it is combined with Bosentan.Approved, Investigational
BosutinibThe serum concentration of Bosutinib can be increased when it is combined with Enasidenib.Approved
Brentuximab vedotinThe serum concentration of Brentuximab vedotin can be increased when it is combined with Enasidenib.Approved
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Enasidenib.Approved, Investigational
BupropionThe metabolism of Enasidenib can be decreased when combined with Bupropion.Approved
CabergolineThe risk or severity of adverse effects can be increased when Cabergoline is combined with Enasidenib.Approved
CaffeineThe metabolism of Enasidenib can be decreased when combined with Caffeine.Approved
CapecitabineThe metabolism of Enasidenib can be decreased when combined with Capecitabine.Approved, Investigational
CarbamazepineThe metabolism of Enasidenib can be increased when combined with Carbamazepine.Approved, Investigational
CelecoxibThe metabolism of Enasidenib can be decreased when combined with Celecoxib.Approved, Investigational
CeritinibThe serum concentration of Enasidenib can be increased when it is combined with Ceritinib.Approved
CerivastatinThe serum concentration of Cerivastatin can be increased when it is combined with Enasidenib.Withdrawn
ChloramphenicolThe metabolism of Enasidenib can be decreased when combined with Chloramphenicol.Approved, Vet Approved
ChloroquineThe metabolism of Enasidenib can be decreased when combined with Chloroquine.Approved, Vet Approved
ChlorpromazineThe metabolism of Enasidenib can be decreased when combined with Chlorpromazine.Approved, Vet Approved
CholecalciferolThe metabolism of Enasidenib can be decreased when combined with Cholecalciferol.Approved, Nutraceutical
CilostazolThe serum concentration of Cilostazol can be increased when it is combined with Enasidenib.Approved
CimetidineThe metabolism of Enasidenib can be decreased when combined with Cimetidine.Approved
CinacalcetThe metabolism of Enasidenib can be decreased when combined with Cinacalcet.Approved
CitalopramThe metabolism of Enasidenib can be decreased when combined with Citalopram.Approved
ClarithromycinThe metabolism of Enasidenib can be decreased when combined with Clarithromycin.Approved
ClemastineThe metabolism of Enasidenib can be decreased when combined with Clemastine.Approved
ClobazamThe metabolism of Enasidenib can be decreased when combined with Clobazam.Approved, Illicit
ClomipramineThe metabolism of Enasidenib can be decreased when combined with Clomipramine.Approved, Vet Approved
ClopidogrelThe metabolism of Enasidenib can be decreased when combined with Clopidogrel.Approved, Nutraceutical
ClotrimazoleThe metabolism of Enasidenib can be decreased when combined with Clotrimazole.Approved, Vet Approved
ClozapineThe metabolism of Enasidenib can be decreased when combined with Clozapine.Approved
CobicistatThe serum concentration of Enasidenib can be increased when it is combined with Cobicistat.Approved
CocaineThe metabolism of Enasidenib can be decreased when combined with Cocaine.Approved, Illicit
ColchicineThe serum concentration of Colchicine can be increased when it is combined with Enasidenib.Approved
ConivaptanThe serum concentration of Enasidenib can be increased when it is combined with Conivaptan.Approved, Investigational
CrisaboroleThe metabolism of Enasidenib can be decreased when combined with Crisaborole.Approved
CrizotinibThe metabolism of Enasidenib can be decreased when combined with Crizotinib.Approved
CyclosporineThe metabolism of Enasidenib can be decreased when combined with Cyclosporine.Approved, Investigational, Vet Approved
Cyproterone acetateThe serum concentration of Enasidenib can be decreased when it is combined with Cyproterone acetate.Approved, Investigational
Dabigatran etexilateThe serum concentration of the active metabolites of Dabigatran etexilate can be increased when Dabigatran etexilate is used in combination with Enasidenib.Approved
DabrafenibThe serum concentration of Enasidenib can be decreased when it is combined with Dabrafenib.Approved
DarifenacinThe metabolism of Enasidenib can be decreased when combined with Darifenacin.Approved, Investigational
DarunavirThe serum concentration of Enasidenib can be increased when it is combined with Darunavir.Approved
DasatinibThe serum concentration of Enasidenib can be increased when it is combined with Dasatinib.Approved, Investigational
DeferasiroxThe serum concentration of Enasidenib can be decreased when it is combined with Deferasirox.Approved, Investigational
DelavirdineThe metabolism of Enasidenib can be decreased when combined with Delavirdine.Approved
DesipramineThe metabolism of Enasidenib can be decreased when combined with Desipramine.Approved
DihydroergocornineThe risk or severity of adverse effects can be increased when Dihydroergocornine is combined with Enasidenib.Approved
DihydroergocristineThe risk or severity of adverse effects can be increased when Dihydroergocristine is combined with Enasidenib.Experimental
DihydroergocryptineThe risk or severity of adverse effects can be increased when Dihydroergocryptine is combined with Enasidenib.Experimental
DihydroergotamineThe metabolism of Enasidenib can be decreased when combined with Dihydroergotamine.Approved
DiltiazemThe metabolism of Enasidenib can be decreased when combined with Diltiazem.Approved
DiphenhydramineThe metabolism of Enasidenib can be decreased when combined with Diphenhydramine.Approved
DosulepinThe metabolism of Enasidenib can be decreased when combined with Dosulepin.Approved
DoxorubicinThe serum concentration of Doxorubicin can be increased when it is combined with Enasidenib.Approved, Investigational
DoxorubicinThe metabolism of Enasidenib can be decreased when combined with Doxorubicin.Approved, Investigational
DoxycyclineThe metabolism of Enasidenib can be decreased when combined with Doxycycline.Approved, Investigational, Vet Approved
DronedaroneThe metabolism of Enasidenib can be decreased when combined with Dronedarone.Approved
DuloxetineThe metabolism of Enasidenib can be decreased when combined with Duloxetine.Approved
EdoxabanThe serum concentration of Edoxaban can be increased when it is combined with Enasidenib.Approved
EfavirenzThe metabolism of Enasidenib can be decreased when combined with Efavirenz.Approved, Investigational
EliglustatThe metabolism of Enasidenib can be decreased when combined with Eliglustat.Approved
EltrombopagThe serum concentration of Enasidenib can be increased when it is combined with Eltrombopag.Approved
EnzalutamideThe serum concentration of Enasidenib can be decreased when it is combined with Enzalutamide.Approved
ErgonovineThe risk or severity of adverse effects can be increased when Ergonovine is combined with Enasidenib.Approved
ErgotamineThe risk or severity of adverse effects can be increased when Ergotamine is combined with Enasidenib.Approved
ErythromycinThe metabolism of Enasidenib can be decreased when combined with Erythromycin.Approved, Vet Approved
Eslicarbazepine acetateThe metabolism of Enasidenib can be decreased when combined with Eslicarbazepine acetate.Approved
EsomeprazoleThe metabolism of Enasidenib can be decreased when combined with Esomeprazole.Approved, Investigational
EtravirineThe metabolism of Enasidenib can be decreased when combined with Etravirine.Approved
EverolimusThe serum concentration of Everolimus can be increased when it is combined with Enasidenib.Approved
FelodipineThe metabolism of Enasidenib can be decreased when combined with Felodipine.Approved, Investigational
FesoterodineThe serum concentration of the active metabolites of Fesoterodine can be increased when Fesoterodine is used in combination with Enasidenib.Approved
FloxuridineThe metabolism of Enasidenib can be decreased when combined with Floxuridine.Approved
FluconazoleThe metabolism of Enasidenib can be decreased when combined with Fluconazole.Approved
FluorouracilThe metabolism of Enasidenib can be decreased when combined with Fluorouracil.Approved
FluoxetineThe metabolism of Enasidenib can be decreased when combined with Fluoxetine.Approved, Vet Approved
FluvastatinThe metabolism of Enasidenib can be decreased when combined with Fluvastatin.Approved
FluvoxamineThe metabolism of Enasidenib can be decreased when combined with Fluvoxamine.Approved, Investigational
FosamprenavirThe metabolism of Enasidenib can be decreased when combined with Fosamprenavir.Approved
FosaprepitantThe serum concentration of Enasidenib can be increased when it is combined with Fosaprepitant.Approved
FosphenytoinThe metabolism of Enasidenib can be increased when combined with Fosphenytoin.Approved
Fusidic AcidThe serum concentration of Enasidenib can be increased when it is combined with Fusidic Acid.Approved
GemfibrozilThe metabolism of Enasidenib can be decreased when combined with Gemfibrozil.Approved
HaloperidolThe metabolism of Enasidenib can be decreased when combined with Haloperidol.Approved
ImatinibThe metabolism of Enasidenib can be decreased when combined with Imatinib.Approved
ImipramineThe metabolism of Enasidenib can be decreased when combined with Imipramine.Approved
IndinavirThe metabolism of Enasidenib can be decreased when combined with Indinavir.Approved
IrbesartanThe metabolism of Enasidenib can be decreased when combined with Irbesartan.Approved, Investigational
IrinotecanThe serum concentration of SN-38 an active metabolite of Irinotecan can be increased when used in combination with Enasidenib.Approved, Investigational
IsavuconazoniumThe metabolism of Enasidenib can be decreased when combined with Isavuconazonium.Approved, Investigational
IsoniazidThe metabolism of Enasidenib can be decreased when combined with Isoniazid.Approved
IsradipineThe metabolism of Enasidenib can be decreased when combined with Isradipine.Approved
ItraconazoleThe metabolism of Enasidenib can be decreased when combined with Itraconazole.Approved, Investigational
IvacaftorThe serum concentration of Enasidenib can be increased when it is combined with Ivacaftor.Approved
KetoconazoleThe metabolism of Enasidenib can be decreased when combined with Ketoconazole.Approved, Investigational
LapatinibThe metabolism of Enasidenib can be decreased when combined with Lapatinib.Approved, Investigational
LedipasvirThe serum concentration of Ledipasvir can be increased when it is combined with Enasidenib.Approved
LeflunomideThe metabolism of Enasidenib can be decreased when combined with Leflunomide.Approved, Investigational
LidocaineThe metabolism of Enasidenib can be decreased when combined with Lidocaine.Approved, Vet Approved
LisurideThe risk or severity of adverse effects can be increased when Lisuride is combined with Enasidenib.Approved, Investigational
LobeglitazoneThe metabolism of Enasidenib can be decreased when combined with Lobeglitazone.Approved, Investigational
LopinavirThe metabolism of Enasidenib can be decreased when combined with Lopinavir.Approved
LorcaserinThe metabolism of Enasidenib can be decreased when combined with Lorcaserin.Approved
LosartanThe metabolism of Enasidenib can be decreased when combined with Losartan.Approved
LovastatinThe metabolism of Enasidenib can be decreased when combined with Lovastatin.Approved, Investigational
LuliconazoleThe serum concentration of Enasidenib can be increased when it is combined with Luliconazole.Approved
LumacaftorThe serum concentration of Enasidenib can be increased when it is combined with Lumacaftor.Approved
LumefantrineThe metabolism of Enasidenib can be decreased when combined with Lumefantrine.Approved
Lysergic Acid DiethylamideThe risk or severity of adverse effects can be increased when Lysergic Acid Diethylamide is combined with Enasidenib.Illicit, Investigational, Withdrawn
ManidipineThe metabolism of Enasidenib can be decreased when combined with Manidipine.Approved, Investigational
MetergolineThe risk or severity of adverse effects can be increased when Metergoline is combined with Enasidenib.Experimental
MethadoneThe metabolism of Enasidenib can be decreased when combined with Methadone.Approved
MethotrimeprazineThe metabolism of Enasidenib can be decreased when combined with Methotrimeprazine.Approved
MethylergometrineThe risk or severity of adverse effects can be increased when Methylergometrine is combined with Enasidenib.Approved
MethysergideThe risk or severity of adverse effects can be increased when Methysergide is combined with Enasidenib.Approved
MetoprololThe serum concentration of Metoprolol can be increased when it is combined with Enasidenib.Approved, Investigational
MevastatinThe serum concentration of Mevastatin can be increased when it is combined with Enasidenib.Experimental
MexiletineThe metabolism of Enasidenib can be decreased when combined with Mexiletine.Approved
MidostaurinThe metabolism of Enasidenib can be decreased when combined with Midostaurin.Approved
MifepristoneThe serum concentration of Enasidenib can be increased when it is combined with Mifepristone.Approved, Investigational
MirabegronThe metabolism of Enasidenib can be decreased when combined with Mirabegron.Approved
MitotaneThe serum concentration of Enasidenib can be decreased when it is combined with Mitotane.Approved
MoclobemideThe metabolism of Enasidenib can be decreased when combined with Moclobemide.Approved
ModafinilThe metabolism of Enasidenib can be decreased when combined with Modafinil.Approved, Investigational
NaloxegolThe serum concentration of Naloxegol can be increased when it is combined with Enasidenib.Approved
NefazodoneThe metabolism of Enasidenib can be decreased when combined with Nefazodone.Approved, Withdrawn
NelfinavirThe metabolism of Enasidenib can be decreased when combined with Nelfinavir.Approved
NetupitantThe serum concentration of Enasidenib can be increased when it is combined with Netupitant.Approved
NevirapineThe metabolism of Enasidenib can be increased when combined with Nevirapine.Approved
NicardipineThe metabolism of Enasidenib can be decreased when combined with Nicardipine.Approved
NicergolineThe risk or severity of adverse effects can be increased when Nicergoline is combined with Enasidenib.Approved, Investigational
NilotinibThe metabolism of Enasidenib can be decreased when combined with Nilotinib.Approved, Investigational
NintedanibThe serum concentration of Nintedanib can be increased when it is combined with Enasidenib.Approved
OlaparibThe metabolism of Enasidenib can be decreased when combined with Olaparib.Approved
OmeprazoleThe metabolism of Enasidenib can be decreased when combined with Omeprazole.Approved, Investigational, Vet Approved
OsimertinibThe serum concentration of Enasidenib can be increased when it is combined with Osimertinib.Approved
PalbociclibThe serum concentration of Enasidenib can be increased when it is combined with Palbociclib.Approved
PanobinostatThe serum concentration of Enasidenib can be increased when it is combined with Panobinostat.Approved, Investigational
PantoprazoleThe metabolism of Enasidenib can be decreased when combined with Pantoprazole.Approved
ParoxetineThe metabolism of Enasidenib can be decreased when combined with Paroxetine.Approved, Investigational
PazopanibThe serum concentration of Pazopanib can be increased when it is combined with Enasidenib.Approved
Peginterferon alfa-2bThe serum concentration of Enasidenib can be decreased when it is combined with Peginterferon alfa-2b.Approved
PentobarbitalThe metabolism of Enasidenib can be increased when combined with Pentobarbital.Approved, Vet Approved
PergolideThe risk or severity of adverse effects can be increased when Pergolide is combined with Enasidenib.Approved, Investigational, Vet Approved, Withdrawn
PhenobarbitalThe metabolism of Enasidenib can be increased when combined with Phenobarbital.Approved
PhenytoinThe metabolism of Enasidenib can be increased when combined with Phenytoin.Approved, Vet Approved
PioglitazoneThe metabolism of Enasidenib can be decreased when combined with Pioglitazone.Approved, Investigational
PitavastatinThe serum concentration of Pitavastatin can be increased when it is combined with Enasidenib.Approved
PosaconazoleThe metabolism of Enasidenib can be decreased when combined with Posaconazole.Approved, Investigational, Vet Approved
PravastatinThe serum concentration of Pravastatin can be increased when it is combined with Enasidenib.Approved
PrimidoneThe metabolism of Enasidenib can be increased when combined with Primidone.Approved, Vet Approved
PromazineThe metabolism of Enasidenib can be decreased when combined with Promazine.Approved, Vet Approved
PrucaloprideThe serum concentration of Prucalopride can be increased when it is combined with Enasidenib.Approved
PyrimethamineThe metabolism of Enasidenib can be decreased when combined with Pyrimethamine.Approved, Vet Approved
QuazepamThe serum concentration of Enasidenib can be increased when it is combined with Quazepam.Approved, Illicit
QuinidineThe metabolism of Enasidenib can be decreased when combined with Quinidine.Approved
QuinineThe metabolism of Enasidenib can be decreased when combined with Quinine.Approved
RabeprazoleThe metabolism of Enasidenib can be decreased when combined with Rabeprazole.Approved, Investigational
RanolazineThe serum concentration of Ranolazine can be increased when it is combined with Enasidenib.Approved, Investigational
RifabutinThe metabolism of Enasidenib can be increased when combined with Rifabutin.Approved
RifampicinThe metabolism of Enasidenib can be increased when combined with Rifampicin.Approved
RifapentineThe metabolism of Enasidenib can be increased when combined with Rifapentine.Approved
RifaximinThe serum concentration of Rifaximin can be increased when it is combined with Enasidenib.Approved, Investigational
RilpivirineThe serum concentration of Rilpivirine can be decreased when it is combined with Enasidenib.Approved
RitonavirThe metabolism of Enasidenib can be decreased when combined with Ritonavir.Approved, Investigational
RolapitantThe serum concentration of Enasidenib can be increased when it is combined with Rolapitant.Approved
RopiniroleThe metabolism of Enasidenib can be decreased when combined with Ropinirole.Approved, Investigational
RosiglitazoneThe metabolism of Enasidenib can be decreased when combined with Rosiglitazone.Approved, Investigational
RosuvastatinThe serum concentration of Rosuvastatin can be increased when it is combined with Enasidenib.Approved
SaquinavirThe metabolism of Enasidenib can be decreased when combined with Saquinavir.Approved, Investigational
SaxagliptinThe serum concentration of Saxagliptin can be decreased when it is combined with Enasidenib.Approved
SecobarbitalThe metabolism of Enasidenib can be increased when combined with Secobarbital.Approved, Vet Approved
SertralineThe metabolism of Enasidenib can be decreased when combined with Sertraline.Approved
SildenafilThe metabolism of Enasidenib can be decreased when combined with Sildenafil.Approved, Investigational
SilodosinThe serum concentration of Silodosin can be increased when it is combined with Enasidenib.Approved
SiltuximabThe serum concentration of Enasidenib can be decreased when it is combined with Siltuximab.Approved
SimeprevirThe serum concentration of Enasidenib can be increased when it is combined with Simeprevir.Approved
SimvastatinThe serum concentration of Simvastatin can be increased when it is combined with Enasidenib.Approved
SorafenibThe metabolism of Enasidenib can be decreased when combined with Sorafenib.Approved, Investigational
St. John's WortThe serum concentration of Enasidenib can be decreased when it is combined with St. John's Wort.Investigational, Nutraceutical
StiripentolThe serum concentration of Enasidenib can be increased when it is combined with Stiripentol.Approved
SulfadiazineThe metabolism of Enasidenib can be decreased when combined with Sulfadiazine.Approved, Vet Approved
SulfamethoxazoleThe metabolism of Enasidenib can be decreased when combined with Sulfamethoxazole.Approved
SulfisoxazoleThe metabolism of Enasidenib can be decreased when combined with Sulfisoxazole.Approved, Vet Approved
TamoxifenThe metabolism of Enasidenib can be decreased when combined with Tamoxifen.Approved
TelaprevirThe metabolism of Enasidenib can be decreased when combined with Telaprevir.Approved, Withdrawn
TelithromycinThe metabolism of Enasidenib can be decreased when combined with Telithromycin.Approved
Tenofovir disoproxilThe metabolism of Enasidenib can be decreased when combined with Tenofovir disoproxil.Approved, Investigational
TerbinafineThe metabolism of Enasidenib can be decreased when combined with Terbinafine.Approved, Investigational, Vet Approved
TergurideThe risk or severity of adverse effects can be increased when Terguride is combined with Enasidenib.Experimental
TeriflunomideThe serum concentration of Enasidenib can be decreased when it is combined with Teriflunomide.Approved
TheophyllineThe metabolism of Enasidenib can be decreased when combined with Theophylline.Approved
ThioridazineThe serum concentration of Thioridazine can be increased when it is combined with Enasidenib.Approved, Withdrawn
ThiotepaThe metabolism of Enasidenib can be decreased when combined with Thiotepa.Approved
TicagrelorThe metabolism of Enasidenib can be decreased when combined with Ticagrelor.Approved
TiclopidineThe metabolism of Enasidenib can be decreased when combined with Ticlopidine.Approved
TipranavirThe metabolism of Enasidenib can be decreased when combined with Tipranavir.Approved, Investigational
TocilizumabThe serum concentration of Enasidenib can be decreased when it is combined with Tocilizumab.Approved
TolbutamideThe metabolism of Enasidenib can be decreased when combined with Tolbutamide.Approved
TopiramateThe metabolism of Enasidenib can be decreased when combined with Topiramate.Approved
TopiroxostatThe metabolism of Enasidenib can be decreased when combined with Topiroxostat.Approved, Investigational
TopotecanThe serum concentration of Topotecan can be increased when it is combined with Enasidenib.Approved, Investigational
TranylcypromineThe metabolism of Enasidenib can be decreased when combined with Tranylcypromine.Approved
TrimethoprimThe metabolism of Enasidenib can be decreased when combined with Trimethoprim.Approved, Vet Approved
UbidecarenoneThe serum concentration of Ubidecarenone can be increased when it is combined with Enasidenib.Approved, Investigational, Nutraceutical
Valproic AcidThe metabolism of Enasidenib can be decreased when combined with Valproic Acid.Approved, Investigational
ValsartanThe metabolism of Enasidenib can be decreased when combined with Valsartan.Approved, Investigational
VenlafaxineThe metabolism of Enasidenib can be decreased when combined with Venlafaxine.Approved
VerapamilThe metabolism of Enasidenib can be decreased when combined with Verapamil.Approved
VincristineThe serum concentration of Vincristine can be increased when it is combined with Enasidenib.Approved, Investigational
VoriconazoleThe metabolism of Enasidenib can be decreased when combined with Voriconazole.Approved, Investigational
ZafirlukastThe metabolism of Enasidenib can be decreased when combined with Zafirlukast.Approved, Investigational
ZiprasidoneThe metabolism of Enasidenib can be decreased when combined with Ziprasidone.Approved
ZucapsaicinThe metabolism of Enasidenib can be decreased when combined with Zucapsaicin.Approved
Food Interactions
Not Available

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. [PubMed:27721426]
  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. [PubMed:28588020]
  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. [PubMed:28588019]
External Links
PubChem Compound
89683805
PubChem Substance
347829326
ChemSpider
38772329
HET
69Q
Wikipedia
Enasidenib
PDB Entries
5i96
FDA label
Download (420 KB)
MSDS
Download (27 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealthy Volunteers2
1RecruitingTreatmentAML Arising After Exposure to Genotoxic Injury / AML Arising From Antecedent Hematologic Disorder (AHD) / AML Arising From Myelodysplastic Syndrome (MDS) / Newly Diagnosed Acute Myeloid Leukemia (AML) / Untreated AML1
1RecruitingTreatmentHepatic Impairment1
1, 2Active Not RecruitingTreatmentNeoplasms, Hematologic1
1, 2CompletedTreatmentAngioimmunoblastic T-Cell Lymphoma / Chondrosarcomas / Gliomas / Intrahepatic Cholangiocarcinoma / Tumors, Solid1
1, 2RecruitingTreatmentLeukemia Acute Myeloid Leukemia (AML)1
1, 2RecruitingTreatmentPreviously Untreated Acute Myeloid Leukemia1
3RecruitingTreatmentIsocitrate Dehydrogenase / Myeloid Leukemias1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral50 mg/1
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US9512107No2013-01-072033-01-07Us
US9732062No2014-09-162034-09-16Us
US9738625No2014-08-012034-08-01Us

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
Not Available

Taxonomy

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
2,4-diamine-s-triazine / Aminopyridine / N-aliphatic s-triazine / Pyridine / 1,3,5-triazine / Tertiary alcohol / Heteroaromatic compound / Azacycle / Hydrocarbon derivative / Alcohol
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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. [PubMed:27721426]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
Human
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
Human
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
Human
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
Human
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
Human
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
Human
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
Human
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

Transporters

Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
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
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Human
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 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
Human
Pharmacological action
Unknown
Actions
Inhibitor
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
Human
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
Human
Pharmacological action
Unknown
Actions
Inhibitor
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 on August 02, 2017 08:49 / Updated on December 01, 2017 17:38