Details of the Drug Combination

General Information of Drug Combination (ID: DCOY10X)

Drug Combination Name

Enasidenib Ivosidenib

Indication

Disease Entry	Status	REF
Acute Myeloid Leukemia	Phase 3	[1]

Component Drugs

Enasidenib DM8QXOC

Ivosidenib DM8S6T7

N.A.

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Enasidenib Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[5]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[6]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[7]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[8]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[9]
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Enasidenib Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Aldo-keto reductase family 1 member C3 (AKR1C3)	OTU2SXBA	AK1C3_HUMAN	Decreases Activity	[10]
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Indication(s) of Ivosidenib

Disease Entry	ICD 11	Status	REF
Acute myeloid leukaemia	2A60	Approved	[2]
Cholangiocarcinoma	2C12.10	Phase 3	[3]
Haematological malignancy	2B33.Y	Phase 1	[4]

Ivosidenib Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Oxalosuccinate decarboxylase (IDH1)	TTV2A1R	IDHC_HUMAN	Inhibitor	[2]
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Ivosidenib Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[11]
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References

1	ClinicalTrials.gov (NCT03839771) A Study of Ivosidenib or Enasidenib in Combination With Induction Therapy and Consolidation Therapy, Followed by Maintenance Therapy in Patients With Newly Diagnosed Acute Myeloid Leukemia or Myedysplastic Syndrome EB2, With an IDH1 or IDH2 Mutation, Respectively, Eligible for Intensive Chemotherapy
2	2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
3	ClinicalTrials.gov (NCT02989857) Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy) (ClarIDHy). U.S. National Institutes of Health.
4	ClinicalTrials.gov (NCT02073994) Study of Orally Administered AG-120 in Subjects With Advanced Solid Tumors, Including Glioma, With an IDH1 Mutation. U.S. National Institutes of Health.
5	FDA Label of Enasidenib. The 2020 official website of the U.S. Food and Drug Administration.
6	FDA Label of Enasidenib. The 2020 official website of the U.S. Food and Drug Administration.
7	FDA Label of Enasidenib. The 2020 official website of the U.S. Food and Drug Administration.
8	FDA Label of Enasidenib. The 2020 official website of the U.S. Food and Drug Administration.
9	Enasidenib for the treatment of acute myeloid leukemia. Expert Rev Clin Pharmacol. 2018 Aug;11(8):755-760.
10	Isocitrate dehydrogenase 2 inhibitor enasidenib synergizes daunorubicin cytotoxicity by targeting aldo-keto reductase 1C3 and ATP-binding cassette transporters. Arch Toxicol. 2022 Dec;96(12):3265-3277. doi: 10.1007/s00204-022-03359-2. Epub 2022 Aug 16.
11	DrugBank 5.0: a major update to the DrugBank database for 2018. Nucleic Acids Res. 2018 Jan 4;46(D1):D1074-D1082. (ID: DB14568)