enasidenib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
isocitrate dehydrogenase inhibitors 5251 1446502-11-9

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • enasidenib
  • enasidenib mesylate
  • AG-221
  • CC-90007 Free Base
  • CC-90007
  • AG-221 mesylate
Enasidenib is a small molecule inhibitor of the isocitrate dehydrogenase 2 (IDH2) enzyme. Enasidenib targets the mutant IDH2 variants R140Q, R172S, and R172K at approximately 40-fold lower concentrations than the wild-type enzyme in vitro. 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.
  • Molecular weight: 473.38
  • Formula: C19H17F6N7O
  • CLOGP: 3.76
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 3
  • TPSA: 108.74
  • ALOGS: -4.11
  • ROTB: 8
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
kinase-safety-class ACVR2B,AXL,BRAF,CAMK2D,EIF2AK3,GRK2,MAPK7,PDK1,PDK2,PDK4,PRKDC 11
kinase-selectivity-class ACVR2B,CAMK2D,DYRK1B,FLT3,IRAK1,IRAK3,LRRK2,PDK1 8
pfas-class PFAS structural alert (1 = True, 0 = False) 1

Approvals:

DateAgencyCompanyOrphan
Aug. 1, 2017 FDA CELGENE CORP

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Differentiation syndrome 401.32 36.81 59 1614 1272 90625502
Death 341.81 36.81 165 1508 456386 90170388
Platelet count decreased 49.47 36.81 31 1642 136938 90489836
Geotrichum infection 44.48 36.81 8 1665 608 90626166
Eastern Cooperative Oncology Group performance status worsened 40.81 36.81 9 1664 1930 90624844
Acute myeloid leukaemia recurrent 40.28 36.81 9 1664 2048 90624726
Nausea 37.22 36.81 70 1603 1110246 89516528

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Death 398.26 37.71 255 1799 470930 42148351
Differentiation syndrome 332.89 37.71 60 1994 1753 42617528
Full blood count decreased 76.95 37.71 31 2023 20529 42598752
Fatigue 51.64 37.71 82 1972 435559 42183722
Platelet count decreased 45.97 37.71 44 2010 138537 42480744
Decreased appetite 43.78 37.71 50 2004 193087 42426194
Haemoglobin abnormal 43.26 37.71 14 2040 4950 42614331
Nausea 37.98 37.71 68 1986 396731 42222550

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Differentiation syndrome 637.52 44.77 100 2228 2944 110584027
Death 628.19 44.77 297 2031 698572 109888399
Febrile neutropenia 72.52 44.77 57 2271 316710 110270261
Sepsis 68.74 44.77 56 2272 327290 110259681
Eastern Cooperative Oncology Group performance status worsened 67.32 44.77 15 2313 2954 110584017
Haemoglobin abnormal 59.63 44.77 17 2311 9021 110577950
Platelet count decreased 53.81 44.77 42 2286 230401 110356570
Blood bilirubin increased 48.23 44.77 26 2302 75946 110511025

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XM01 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Isocitrate dehydrogenase (IDH) inhibitors
FDA MoA N0000193614 Isocitrate Dehydrogenase 2 Inhibitors
FDA EPC N0000193615 Isocitrate Dehydrogenase 2 Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:145410 EC 1.1.1.42 (isocitrate dehydrogenase) inhibitor

Related Drugs by ATC class:

L01XM Isocitrate dehydrogenase (IDH) inhibitors 3 drugs
ivosidenibolutasidenibvorasidenib

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Acute myeloid leukemia, disease indication 91861009




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.77 Basic
pKa2 2.61 Basic
pKa3 0.4 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 100MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 10610125 June 21, 2030 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 50MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 10610125 June 21, 2030 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 100MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 10294215 Jan. 7, 2033 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 100MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 9512107 Jan. 7, 2033 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 50MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 10294215 Jan. 7, 2033 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 50MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 9512107 Jan. 7, 2033 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 100MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 10093654 Aug. 1, 2034 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION
EQ 50MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL 10093654 Aug. 1, 2034 TREATMENT OF RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA (AML) WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Isocitrate dehydrogenase [NADP], mitochondrial Enzyme INHIBITOR IC50 7 SCIENTIFIC LITERATURE DRUG LABEL
Isocitrate dehydrogenase [NADP] cytoplasmic Enzyme IC50 5.30 CHEMBL

External reference:

IDSource
3T1SS4E7AG UNII
1650550-25-6 SECONDARY_CAS_RN
4036873 VANDF
C4519428 UMLSCUI
CHEBI:145374 CHEBI
69Q PDB_CHEM_ID
CHEMBL3989908 ChEMBL_ID
89683805 PUBCHEM_CID
DB13874 DRUGBANK_ID
D10901 KEGG_DRUG
CHEMBL3989931 ChEMBL_ID
10162 INN_ID
C000605269 MESH_SUPPLEMENTAL_RECORD_UI
8960 IUPHAR_LIGAND_ID
763038001 SNOMEDCT_US
763039009 SNOMEDCT_US
763583008 SNOMEDCT_US
32972 MMSL
d08627 MMSL
017290 NDDF
017291 NDDF
1940331 RXNORM
3T1SS4E7AG INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Idhifa HUMAN PRESCRIPTION DRUG LABEL 1 59572-705 TABLET, FILM COATED 50 mg ORAL NDA 27 sections
Idhifa HUMAN PRESCRIPTION DRUG LABEL 1 59572-710 TABLET, FILM COATED 100 mg ORAL NDA 27 sections