Details of the Drug Combination

General Information of Drug Combination (ID: DCJZ273)

Drug Combination Name
Hyodeoxycholic acid Diazoxide
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Hyodeoxycholic acid   DMSIWD0 Diazoxide   DML1538
N.A. Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL
High-throughput Screening Result Testing Cell Line: KBM-7
Zero Interaction Potency (ZIP) Score: 2.76
Bliss Independence Score: 2.76
Loewe Additivity Score: 5.5
LHighest Single Agent (HSA) Score: 5.5

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Hyodeoxycholic acid Interacts with 2 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A6 (UGT1A6) DESD26P UD16_HUMAN Metabolism [6]
UDP-glucuronosyltransferase 2A3 (UGT2A3) DEWBT6H UD2A3_HUMAN Metabolism [7]
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Indication(s) of Diazoxide
Disease Entry ICD 11 Status REF
Congenital hyperinsulinism 5A4Y Approved [2]
Hyperinsulinemia 5A4Y Approved [2]
Hypertension BA00-BA04 Approved [3]
Hypertensive emergency BA03 Approved [2]
Insulinoma 2C10.1 Approved [2]
Malignant essential hypertension BA00 Approved [2]
Diazoxide Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Potassium channel unspecific (KC) TT1VOHK NOUNIPROTAC Modulator [8]
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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 [9]
Interleukin-6 (IL6) OTUOSCCU IL6_HUMAN Decreases Secretion [9]
Nuclear factor NF-kappa-B p105 subunit (NFKB1) OTNRRD8I NFKB1_HUMAN Increases Activity [10]
Interleukin-10 (IL10) OTIRFRXC IL10_HUMAN Decreases Secretion [9]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Decreases Expression [11]
Catenin beta-1 (CTNNB1) OTZ932A3 CTNB1_HUMAN Decreases Expression [11]
Bcl-2-like protein 1 (BCL2L1) OTRC5K9O B2CL1_HUMAN Increases Expression [10]
ATP-sensitive inward rectifier potassium channel 11 (KCNJ11) OTPUUELV KCJ11_HUMAN Decreases Expression [12]
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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 Diazoxide 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: 2409).
4 Complementary deoxyribonucleic acid cloning and expression of a human liver uridine diphosphate-glucuronosyltransferase glucuronidating carboxylic acid-containing drugs. J Pharmacol Exp Ther. 1993 Jan;264(1):475-9.
5 Isolation and characterization of hyodeoxycholic-acid: UDP-glucuronosyltransferase from human liver. Eur J Biochem. 1991 Sep 1;200(2):393-400. doi: 10.1111/j.1432-1033.1991.tb16197.x.
6 Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev. 1999 Nov;31(4):817-99.
7 Novel polymorphic human UDP-glucuronosyltransferase 2A3: cloning, functional characterization of enzyme variants, comparative tissue expression, and gene induction. Mol Pharmacol. 2008 Sep;74(3):744-54.
8 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
9 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.
10 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.
11 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.
12 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.