Details of the Drug Combination

General Information of Drug Combination (ID: DCLPALM)

Drug Combination Name

Fedratinib Enasidenib

Indication

Disease Entry	Status	REF
IDH Mutation	Phase 1	[1]

Component Drugs

Fedratinib DM4ZBK6

Enasidenib DM8QXOC

Small molecular drug

N.A.

2D MOL

3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)

Indication(s) of Fedratinib

Disease Entry	ICD 11	Status	REF
Myelofibrosis	2A20.2	Approved	[2]
Polycythemia vera	2A20.4	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]

Fedratinib Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Janus kinase 2 (JAK-2)	TTRMX3V	JAK2_HUMAN	Inhibitor	[2]
HUMAN janus kinase 2 (JAK-2)	TT0F5HE	JAK2_HUMAN	Inhibitor	[4]
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Fedratinib Interacts with 4 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Suppressor of cytokine signaling 3 (SOCS3)	OTY183WJ	SOCS3_HUMAN	Decreases Expression	[6]
Myc proto-oncogene protein (MYC)	OTPV5LUK	MYC_HUMAN	Decreases Expression	[5]
G1/S-specific cyclin-D1 (CCND1)	OT8HPTKJ	CCND1_HUMAN	Decreases Expression	[5]
Bcl-2-like protein 1 (BCL2L1)	OTRC5K9O	B2CL1_HUMAN	Increases Expression	[5]
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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	[7]
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[8]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[9]
Cytochrome P450 2B6 (CYP2B6)	DEPKLMQ	CP2B6_HUMAN	Metabolism	[10]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[11]
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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	[12]
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References

1	ClinicalTrials.gov (NCT04955938) A Study of Fedratinib With IDH Inhibition in Advanced-Phase, IDH-Mutated Ph-Negative Myeloproliferative Neoplasms
2	Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
3	FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (NDA) 212327
4	TH17 responses in cytokine storm of COVID-19: An emerging target of JAK2 inhibitor Fedratinib. J Microbiol Immunol Infect. 2020 Mar 11. pii: S1684-1182(20)30065-7.
5	Differences in gene expression and alterations in cell cycle of acute myeloid leukemia cell lines after treatment with JAK inhibitors. Eur J Pharmacol. 2015 Oct 15;765:188-97. doi: 10.1016/j.ejphar.2015.08.037. Epub 2015 Aug 20.
6	The antimicrobial drug pyrimethamine inhibits STAT3 transcriptional activity by targeting the enzyme dihydrofolate reductase. J Biol Chem. 2022 Feb;298(2):101531. doi: 10.1016/j.jbc.2021.101531. Epub 2021 Dec 23.
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	FDA Label of Enasidenib. The 2020 official website of the U.S. Food and Drug Administration.
10	FDA Label of Enasidenib. The 2020 official website of the U.S. Food and Drug Administration.
11	Enasidenib for the treatment of acute myeloid leukemia. Expert Rev Clin Pharmacol. 2018 Aug;11(8):755-760.
12	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.