enasidenib 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | 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

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 351.07 37.27 53 1465 1050 63486454
Death 279.87 37.27 147 1371 374234 63113270
Platelet count decreased 46.84 37.27 31 1487 116091 63371413
Acute myeloid leukaemia recurrent 40.08 37.27 9 1509 1614 63485890

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 357.66 39.02 233 1643 397816 34557239
Differentiation syndrome 313.80 39.02 56 1820 1382 34953673
Full blood count decreased 74.12 39.02 30 1846 18058 34936997
Fatigue 49.39 39.02 78 1798 370575 34584480
Platelet count decreased 47.46 39.02 44 1832 119673 34835382
Haemoglobin abnormal 45.17 39.02 14 1862 3866 34951189
Decreased appetite 43.78 39.02 49 1827 166343 34788712
Neutrophil count abnormal 40.61 39.02 11 1865 1891 34953164

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 564.34 40.94 90 1935 2434 79739929
Death 507.52 40.94 255 1770 566259 79176104
Febrile neutropenia 72.32 40.94 54 1971 230945 79511418
Sepsis 67.06 40.94 55 1970 269373 79472990
Eastern Cooperative Oncology Group performance status worsened 64.32 40.94 14 2011 2051 79740312
Haemoglobin abnormal 56.12 40.94 16 2009 7038 79735325
Platelet count decreased 53.15 40.94 42 1983 194622 79547741

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC L01XX59 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
OTHER ANTINEOPLASTIC AGENTS
Other antineoplastic agents
FDA MoA N0000193614 Isocitrate Dehydrogenase 2 Inhibitors
FDA EPC N0000193615 Isocitrate Dehydrogenase 2 Inhibitor
CHEBI has role CHEBI:35610 antineoplastic agents
CHEBI has role CHEBI:145410 IDP1 inhibitors

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 100MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL Aug. 1, 2024 TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION AS DETECTED BY AN FDA-APPROVED TEST
EQ 50MG BASE IDHIFA BRISTOL MYERS SQUIBB N209606 Aug. 1, 2017 RX TABLET ORAL Aug. 1, 2024 TREATMENT OF ADULT PATIENTS WITH RELAPSED OR REFRACTORY ACUTE MYELOID LEUKEMIA WITH AN ISOCITRATE DEHYDROGENASE-2 (IDH2) MUTATION AS DETECTED BY AN FDA-APPROVED TEST

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
8960 IUPHAR_LIGAND_ID
32972 MMSL
d08627 MMSL
017290 NDDF
017291 NDDF
763038001 SNOMEDCT_US
763039009 SNOMEDCT_US
763583008 SNOMEDCT_US
1940331 RXNORM
C000605269 MESH_SUPPLEMENTAL_RECORD_UI

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Idhifa HUMAN PRESCRIPTION DRUG LABEL 1 59572-705 TABLET, FILM COATED 50 mg ORAL NDA 29 sections
Idhifa HUMAN PRESCRIPTION DRUG LABEL 1 59572-705 TABLET, FILM COATED 50 mg ORAL NDA 29 sections
Idhifa HUMAN PRESCRIPTION DRUG LABEL 1 59572-710 TABLET, FILM COATED 100 mg ORAL NDA 29 sections
Idhifa HUMAN PRESCRIPTION DRUG LABEL 1 59572-710 TABLET, FILM COATED 100 mg ORAL NDA 29 sections