Details of the Drug Combination

General Information of Drug Combination (ID: DCYS7BQ)

• Drug Combination Name: INCB24360 + Idarubicin
• Indication: AML; Status: Phase 1 [1]
• Component Drugs:
  INCB24360 (DMIJGT9): Small molecular drug
  Idarubicin (DMM0XGL): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of INCB24360

Disease Entry	ICD 11	Status	REF
Urothelial carcinoma	2C92.0	Phase 3	[2]
Melanoma	2C30	Phase 2	[3]
Solid tumour/cancer	2A00-2F9Z	Phase 2	[4]
B-cell lymphoma	2A86	Phase 1	[3]
Colorectal cancer	2B91.Z	Phase 1	[3]
Head and neck cancer	2D42	Phase 1	[3]
Lung cancer	2C25.0	Phase 1	[3]
Lymphoma	2A80-2A86	Phase 1	[3]
Merkel cell carcinoma	2C34	Phase 1	[3]
Ovarian cancer	2C73	Phase 1	[3]
Recurrent glioblastoma	2A00.00	Phase 1	[5]

INCB24360 Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Indoleamine 2,3-dioxygenase 1 (IDO1)	TTZJYKH	I23O1_HUMAN	Inhibitor	[8]

INCB24360 Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Indoleamine 2,3-dioxygenase 1 (IDO1)	OT91DBN7	I23O1_HUMAN	Decreases Activity	[9]

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[6]
Acute myeloid leukaemia	2A60	Approved	[7]
Adult acute monocytic leukemia	N.A.	Approved	[6]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[6]
Leukemia	N.A.	Approved	[6]

Idarubicin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
DNA topoisomerase II (TOP2)	TT0IHXV	TOP2A_HUMAN; TOP2B_HUMAN	Modulator	[11]

Idarubicin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 1 (ABCC1)	DTSYQGK	MRP1_HUMAN	Substrate	[12]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[13]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[13]

Idarubicin Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[14]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[14]

Idarubicin Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Decreases Activity	[10]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[15]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[10]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[16]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Activity	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[17]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Decreases Activity	[10]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[18]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[10]

References

• [1] ClinicalTrials.gov (NCT03444649) Epacadostat, Idarubicin and Cytarabine (EIC) in AML
• [2] ClinicalTrials.gov (NCT03361865) Pembrolizumab in Combination With Epacadostat or Placebo in Cisplatin-ineligible Urothelial Carcinoma (KEYNOTE-672/ECHO-307). U.S. National Institutes of Health.
• [3] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 8221).
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Idarubicin FDA Label
• [7] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7083).
• [8] Incyte. Product Development Pipeline.
• [9] Salinomycin promotes T-cell proliferation by inhibiting the expression and enzymatic activity of immunosuppressive indoleamine-2,3-dioxygenase in human breast cancer cells. Toxicol Appl Pharmacol. 2020 Oct 1;404:115203. doi: 10.1016/j.taap.2020.115203. Epub 2020 Aug 19.
• [10] Quantitative high-throughput profiling of environmental chemicals and drugs that modulate farnesoid X receptor. Sci Rep. 2014 Sep 26;4:6437. doi: 10.1038/srep06437.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [13] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [14] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [15] A Quantitative Approach to Screen for Nephrotoxic Compounds In Vitro. J Am Soc Nephrol. 2016 Apr;27(4):1015-28. doi: 10.1681/ASN.2015010060. Epub 2015 Aug 10.
• [16] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
• [17] The induction of apoptosis by daunorubicin and idarubicin in human trisomic and diabetic fibroblasts. Cell Mol Biol Lett. 2008;13(2):182-94. doi: 10.2478/s11658-007-0045-7. Epub 2008 Apr 10.
• [18] Refining the human iPSC-cardiomyocyte arrhythmic risk assessment model. Toxicol Sci. 2013 Dec;136(2):581-94. doi: 10.1093/toxsci/kft205. Epub 2013 Sep 19.