Details of the Drug Combination

General Information of Drug Combination (ID: DCPL6GD)

• Drug Combination Name: Rifampin + Hydralazine
• Indication: Chronic myelogenous leukemia; Status: Investigative [1]
• Component Drugs:
  Rifampin (DMA8J1G): Small molecular drug
  Hydralazine (DMU8JGH): Small molecular drug
• High-throughput Screening Result:
  Testing Cell Line: KBM-7
  Zero Interaction Potency (ZIP) Score: 48.34
  Bliss Independence Score: 48.34
  Loewe Additivity Score: 64.15
  LHighest Single Agent (HSA) Score: 64.15

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Rifampin

Disease Entry	ICD 11	Status	REF
Tuberculosis	1B10-1B1Z	Approved	[2]

Rifampin Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Bacterial RNA polymerase switch region (Bact RNAP-SR)	TTIJ5EB	NOUNIPROTAC	Inhibitor	[5]

Rifampin Interacts with 5 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Multidrug resistance-associated protein 2 (ABCC2)	DTFI42L	MRP2_HUMAN	Substrate	[6]
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[8]
Organic anion transporting polypeptide 1B1 (SLCO1B1)	DT3D8F0	SO1B1_HUMAN	Substrate	[9]
Organic anion transporting polypeptide 1B3 (SLCO1B3)	DT9C1TS	SO1B3_HUMAN	Substrate	[10]

Indication(s) of Hydralazine

Disease Entry	ICD 11	Status	REF
Chronic heart failure	BD1Z	Approved	[3]
Hypertension	BA00-BA04	Approved	[4]
Malignant essential hypertension	BA00	Approved	[3]

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	[11]

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	[12]
N-acetyltransferase 1 (NAT1)	DE7OAB3	ARY1_HUMAN	Metabolism	[13]
N-acetyltransferase 2 (NAT2)	DER7TA0	ARY2_HUMAN	Metabolism	[13]

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	[14]
Estrogen receptor (ESR1)	OTKLU61J	ESR1_HUMAN	Increases Expression	[15]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Increases Expression	[15]
Retinoic acid receptor beta (RARB)	OT367U3E	RARB_HUMAN	Decreases Methylation	[15]
Methylated-DNA--protein-cysteine methyltransferase (MGMT)	OT40A9WH	MGMT_HUMAN	Increases Expression	[15]
Adenomatous polyposis coli protein (APC)	OTKV0TIK	APC_HUMAN	Decreases Methylation	[15]
Cyclin-dependent kinase inhibitor 2A (CDKN2A)	OTN0ZWAE	CDN2A_HUMAN	Decreases Methylation	[15]
Bis(5'-adenosyl)-triphosphatase (FHIT)	OTGWBSLA	FHIT_HUMAN	Increases Expression	[15]
Death-associated protein kinase 1 (DAPK1)	OTNCNUCO	DAPK1_HUMAN	Increases Expression	[15]
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[16]
Tumor necrosis factor (TNF)	OT4IE164	TNFA_HUMAN	Decreases Secretion	[17]
Collagen alpha-1(I) chain (COL1A1)	OTI31178	CO1A1_HUMAN	Decreases Expression	[18]
Albumin (ALB)	OTVMM513	ALBU_HUMAN	Affects Binding	[19]
Cellular tumor antigen p53 (TP53)	OTIE1VH3	P53_HUMAN	Increases Activity	[20]
Interleukin-6 (IL6)	OTUOSCCU	IL6_HUMAN	Decreases Secretion	[17]
Interleukin-10 (IL10)	OTIRFRXC	IL10_HUMAN	Increases Secretion	[17]

References

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• [2] Drugs used to treat Parkinson's disease, present status and future directions. CNS Neurol Disord Drug Targets. 2008 Oct;7(4):321-42.
• [3] Hydralazine FDA Label
• [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: 7326).
• [5] Bacillus subtilis tolerance of moderate concentrations of rifampin involves the sigma(B)-dependent general and multiple stress response. J Bacteriol. 2002 Jan;184(2):459-67.
• [6] Expression and distribution of CYP3A genes, CYP2B22, and MDR1, MRP1, MRP2, LRP efflux transporters in brain of control and rifampicin-treated pigs. Mol Cell Biochem. 2010 Apr;337(1-2):133-43.
• [7] Mammalian drug efflux transporters of the ATP binding cassette (ABC) family in multidrug resistance: A review of the past decade. Cancer Lett. 2016 Jan 1;370(1):153-64.
• [8] Arginine-482 is not essential for transport of antibiotics, primary bile acids and unconjugated sterols by the human breast cancer resistance protein (ABCG2). Biochem J. 2005 Jan 15;385(Pt 2):419-26.
• [9] Human organic anion transporting polypeptide-C (SLC21A6) is a major determinant of rifampin-mediated pregnane X receptor activation. J Pharmacol Exp Ther. 2003 Jan;304(1):223-8.
• [10] Interactions of rifamycin SV and rifampicin with organic anion uptake systems of human liver. Hepatology. 2002 Jul;36(1):164-72.
• [11] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [12] Prizidilol, an antihypertensive with precapillary vasodilator and beta-adrenoceptor blocking actions, in primary hypertension. Clin Pharmacol Ther. 1981 May;29(5):588-93.
• [13] N-acetyltransferase 2 genotype-dependent N-acetylation of hydralazine in human hepatocytes. Drug Metab Dispos. 2017 Dec;45(12):1276-1281.
• [14] 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.
• [15] A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes. BMC Cancer. 2005 Apr 29;5:44.
• [16] Sympathetic activity in idiopathic dilated cardiomyopathy. Influence of captopril and hydralazine. Cardiovasc Drugs Ther. 1987 Aug;1(2):177-81. doi: 10.1007/BF02125471.
• [17] 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.
• [18] 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.
• [19] 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.
• [20] 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.