Details of the Drug Combination

General Information of Drug Combination (ID: DCJB4CG)

• Drug Combination Name: Oseltamivir + Hydralazine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Oseltamivir (DMGO72P): Small molecular drug
  Hydralazine (DMU8JGH): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 31.25
  Bliss Independence Score: 31.25
  Loewe Additivity Score: 51.12
  LHighest Single Agent (HSA) Score: 51.14

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Oseltamivir

Disease Entry	ICD 11	Status	REF
Influenza	1E30-1E32	Approved	[2]
Influenza virus infection	1E30-1E32	Approved	[3]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 3	[4]

Oseltamivir Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Influenza Neuraminidase (Influ NA)	TT50QJ3	NRAM_I33A0	Inhibitor	[7]

Oseltamivir Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]
Multidrug resistance-associated protein 4 (ABCC4)	DTCSGPB	MRP4_HUMAN	Substrate	[9]
Peptide transporter 1 (SLC15A1)	DT9G7XN	S15A1_HUMAN	Substrate	[10]
Organic anion transporter 1 (SLC22A6)	DTQ23VB	S22A6_HUMAN	Substrate	[11]
Organic anion transporter 3 (SLC22A8)	DTVP67E	S22A8_HUMAN	Substrate	[11]

Oseltamivir Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[12]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Increases Metabolism	[13]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Response To Substance	[14]

Indication(s) of Hydralazine

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[5]
Hypertension	BA00-BA04	Approved	[6]
Malignant essential hypertension	BA00	Approved	[5]

Hydralazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Membrane copper amine oxidase (AOC3)	TT7HC21	AOC3_HUMAN	Modulator	[15]

Hydralazine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[16]
N-acetyltransferase 1 (NAT1)	DE7OAB3	ARY1_HUMAN	Metabolism	[17]
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Metabolism	[17]

Hydralazine Interacts with 16 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Arylamine N-acetyltransferase 2 (NAT2)	OTBPDQOY	ARY2_HUMAN	Increases Acetylation	[18]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[19]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Expression	[19]
Retinoic acid receptor beta (RARB)	OT367U3E	RARB_HUMAN	Decreases Methylation	[19]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Increases Expression	[19]
Adenomatous polyposis coli protein (APC)	OTKV0TIK	APC_HUMAN	Decreases Methylation	[19]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Methylation	[19]
Bis(5'-adenosyl)-triphosphatase (FHIT)	OTGWBSLA	FHIT_HUMAN	Increases Expression	[19]
Death-associated protein kinase 1 (DAPK1)	OTNCNUCO	DAPK1_HUMAN	Increases Expression	[19]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[20]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[21]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[22]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[23]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[24]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[21]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[21]

References

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• [5] Hydralazine FDA Label
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• [10] Oseltamivir (tamiflu) is a substrate of peptide transporter 1. Drug Metab Dispos. 2009 Aug;37(8):1676-81.
• [11] FDA Drug Development and Drug Interactions
• [12] An in vitro coculture system of human peripheral blood mononuclear cells with hepatocellular carcinoma-derived cells for predicting drug-induced liver injury. Arch Toxicol. 2021 Jan;95(1):149-168. doi: 10.1007/s00204-020-02882-4. Epub 2020 Aug 20.
• [13] In vitro inhibition of carboxylesterase 1 by Kava (Piper methysticum) Kavalactones. Chem Biol Interact. 2022 Apr 25;357:109883. doi: 10.1016/j.cbi.2022.109883. Epub 2022 Mar 9.
• [14] Interleukin-6 alters the cellular responsiveness to clopidogrel, irinotecan, and oseltamivir by suppressing the expression of carboxylesterases HCE1 and HCE2. Mol Pharmacol. 2007 Sep;72(3):686-94. doi: 10.1124/mol.107.036889. Epub 2007 May 30.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [16] Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension. Clin Pharmacol Ther. 1981 May;29(5):588-93.
• [17] N-acetyltransferase 2 genotype-dependent N-acetylation of hydralazine in human hepatocytes. Drug Metab Dispos. 2017 Dec;45(12):1276-1281.
• [18] Eukaryotic arylamine N-acetyltransferase. Investigation of substrate specificity by high-throughput screening. Biochem Pharmacol. 2005 Jan 15;69(2):347-59. doi: 10.1016/j.bcp.2004.09.014. Epub 2004 Nov 24.
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• [20] Sympathetic activity in idiopathic dilated cardiomyopathy. Influence of captopril and hydralazine. Cardiovasc Drugs Ther. 1987 Aug;1(2):177-81. doi: 10.1007/BF02125471.
• [21] Antihypertensive drugs clonidine, diazoxide, hydralazine and furosemide regulate the production of cytokines by placentas and peripheral blood mononuclear cells in normal pregnancy. J Hypertens. 2006 May;24(5):915-22. doi: 10.1097/01.hjh.0000222762.84605.03.
• [22] Hydralazine inhibits human peritoneal mesothelial cell proliferation and collagen synthesis. Nephrol Dial Transplant. 1996 Nov;11(11):2276-81. doi: 10.1093/oxfordjournals.ndt.a027148.
• [23] Albumin Protects Lung Cells against Acrolein Cytotoxicity and Acrolein-Adducted Albumin Increases Heme Oxygenase 1 Transcripts. Chem Res Toxicol. 2020 Jul 20;33(7):1969-1979. doi: 10.1021/acs.chemrestox.0c00146. Epub 2020 Jun 29.
• [24] High-throughput measurement of the Tp53 response to anticancer drugs and random compounds using a stably integrated Tp53-responsive luciferase reporter. Carcinogenesis. 2002 Jun;23(6):949-57. doi: 10.1093/carcin/23.6.949.