Details of the Drug Combination

General Information of Drug Combination (ID: DC9U1VH)

Drug Combination Name
Rifampin Diazoxide
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Rifampin   DMA8J1G Diazoxide   DML1538
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL is unavailable 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 5.12
Bliss Independence Score: 5.12
Loewe Additivity Score: 5.91
LHighest Single Agent (HSA) Score: 5.91

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
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]
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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]
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Indication(s) of Diazoxide
Disease Entry ICD 11 Status REF
Congenital hyperinsulinism 5A4Y Approved [3]
Hyperinsulinemia 5A4Y Approved [3]
Hypertension BA00-BA04 Approved [4]
Hypertensive emergency BA03 Approved [3]
Insulinoma 2C10.1 Approved [3]
Malignant essential hypertension BA00 Approved [3]
Diazoxide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Modulator [11]
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Diazoxide Interacts with 8 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tumor necrosis factor (TNF) OT4IE164 TNFA_HUMAN Decreases Secretion [12]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [12]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Activity [13]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [12]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [14]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [14]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [13]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11) OTPUUELV KCJ11_HUMAN Decreases Expression [15]
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⏷ Show the Full List of 8 DOT(s)

References

1 Recurrent recessive mutation in deoxyguanosine kinase causes idiopathic noncirrhotic portal hypertension.Hepatology. 2016 Jun;63(6):1977-86. doi: 10.1002/hep.28499. Epub 2016 Mar 31.
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 Diazoxide 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: 2409).
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 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.
13 Diazoxide-mediated preconditioning against apoptosis involves activation of cAMP-response element-binding protein (CREB) and NFkappaB. J Biol Chem. 2004 Nov 5;279(45):46748-54. doi: 10.1074/jbc.M406217200. Epub 2004 Aug 23.
14 Diazoxide-mediated growth inhibition in human lung cancer cells via downregulation of beta-catenin-mediated cyclin D1 transcription. Lung. 2009 Jan-Feb;187(1):61-7. doi: 10.1007/s00408-008-9127-1. Epub 2008 Dec 4.
15 Combined contributions of over-secreted glucagon-like peptide 1 and suppressed insulin secretion to hyperglycemia induced by gatifloxacin in rats. Toxicol Appl Pharmacol. 2013 Feb 1;266(3):375-84. doi: 10.1016/j.taap.2012.11.015. Epub 2012 Nov 28.