Details of the Drug Combination

General Information of Drug Combination (ID: DCABQHO)

• Drug Combination Name: Idarubicin + Buspirone
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Idarubicin (DMM0XGL): Small molecular drug
  Buspirone (DMBS632): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 22.14
  Bliss Independence Score: 22.14
  Loewe Additivity Score: 30.83
  LHighest Single Agent (HSA) Score: 30.83

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Idarubicin

Disease Entry	ICD 11	Status	REF
Acute myelogenous leukaemia	2A41	Approved	[2]
Acute myeloid leukaemia	2A60	Approved	[3]
Adult acute monocytic leukemia	N.A.	Approved	[2]
Childhood acute megakaryoblastic leukemia	N.A.	Approved	[2]
Leukemia	N.A.	Approved	[2]

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	[6]

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	[7]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]

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	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[9]

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	[5]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[10]
Androgen receptor (AR)	OTUBKAZZ	ANDR_HUMAN	Increases Activity	[5]
Natriuretic peptides B (NPPB)	OTSN2IPY	ANFB_HUMAN	Increases Expression	[11]
Peroxisome proliferator-activated receptor gamma (PPARG)	OTHMARHO	PPARG_HUMAN	Decreases Activity	[5]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[12]
Peroxisome proliferator-activated receptor delta (PPARD)	OTI4WTOP	PPARD_HUMAN	Decreases Activity	[5]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[13]
Bile acid receptor (NR1H4)	OTWZLPTB	NR1H4_HUMAN	Decreases Activity	[5]

Indication(s) of Buspirone

Disease Entry	ICD 11	Status	REF
Anxiety disorder	6B00-6B0Z	Approved	[4]

Buspirone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Agonist	[14]

Buspirone Interacts with 5 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[15]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[16]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[16]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[17]
Cytochrome P450 102A1 (cyp102)	DE4OGUF	CPXB_BACMB	Metabolism	[18]

Buspirone Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Increases Oxidation	[16]
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Oxidation	[16]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[19]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[20]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[20]

References

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• [2] Idarubicin FDA Label
• [3] 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).
• [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: 36).
• [5] 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.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
• [8] Amonafide L-malate is not a substrate for multidrug resistance proteins in secondary acute myeloid leukemia. Leukemia. 2008 Nov;22(11):2110-5.
• [9] In vitro evaluation of cytochrome P450-mediated drug interactions between cytarabine, idarubicin, itraconazole and caspofungin. Hematology. 2004 Jun;9(3):217-21.
• [10] 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.
• [11] The use of biochemical markers in cardiotoxicity monitoring in patients treated for leukemia. Neoplasma. 2005;52(5):430-4.
• [12] 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.
• [13] 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.
• [14] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [15] Effects of cytochrome P450 (CYP) 3A4 inhibitors on the anxiolytic action of tandospirone in rat contextual conditioned fear. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):926-31.
• [16] Cytochrome P450 3A-mediated metabolism of buspirone in human liver microsomes. Drug Metab Dispos. 2005 Apr;33(4):500-7.
• [17] Drug Interactions Flockhart Table
• [18] The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 2007 Jul;25(7):289-98.
• [19] Effect of common medications on the expression of SARS-CoV-2 entry receptors in liver tissue. Arch Toxicol. 2020 Dec;94(12):4037-4041. doi: 10.1007/s00204-020-02869-1. Epub 2020 Aug 17.
• [20] Hormonal responses to the 5-HT1A agonist buspirone in remitted endogenous depressive patients after long-term imipramine treatment. Psychoneuroendocrinology. 2010 May;35(4):481-9. doi: 10.1016/j.psyneuen.2009.08.012. Epub 2009 Sep 16.