Details of the Drug Combination

General Information of Drug Combination (ID: DCIGP8X)

Drug Combination Name
Hyodeoxycholic acid Spironolactone
Indication
Disease Entry Status REF
Chronic myelogenous leukemia Investigative [1]
Component Drugs Hyodeoxycholic acid   DMSIWD0 Spironolactone   DM2AQ5N
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: 4.89
Bliss Independence Score: 4.89
Loewe Additivity Score: 8.04
LHighest Single Agent (HSA) Score: 8.05

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 [7]
UDP-glucuronosyltransferase 2A3 (UGT2A3) DEWBT6H UD2A3_HUMAN Metabolism [8]
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Indication(s) of Spironolactone
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [2]
Congestive heart failure BD10 Approved [3]
Edema MG29 Approved [2]
Hyperaldosteronism 5A72 Approved [2]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Spironolactone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Mineralocorticoid receptor (MR) TT26PHO MCR_HUMAN Modulator [9]
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Spironolactone Interacts with 9 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Bile salt export pump (ABCB11) OTRU7THO ABCBB_HUMAN Decreases Activity [10]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Expression [11]
Collagen alpha-1(III) chain (COL3A1) OTT1EMLM CO3A1_HUMAN Decreases Expression [11]
Plasminogen activator inhibitor 1 (SERPINE1) OTT0MPQ3 PAI1_HUMAN Decreases Expression [12]
ATP-dependent translocase ABCB1 (ABCB1) OTEJROBO MDR1_HUMAN Increases Expression [13]
Myb-related protein A (MYBL1) OTBJMC2P MYBA_HUMAN Increases Expression [14]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Expression [11]
Protein GREB1 (GREB1) OTU6ZA26 GREB1_HUMAN Increases Expression [14]
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Response To Substance [15]
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⏷ Show the Full List of 9 DOT(s)

References

1 CheMBL Affinity Phenotypic Cellular Interaction Assay ID: CHEMBL1125966
2 Spironolactone 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: 2875).
4 Spironolactone in Covid-19 Induced ARDS
5 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.
6 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.
7 Structural and functional studies of UDP-glucuronosyltransferases. Drug Metab Rev. 1999 Nov;31(4):817-99.
8 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.
9 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
10 Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43.
11 Effect of spironolactone on plasma brain natriuretic peptide and left ventricular remodeling in patients with congestive heart failure. J Am Coll Cardiol. 2001 Apr;37(5):1228-33. doi: 10.1016/s0735-1097(01)01116-0.
12 Effect of spironolactone on impaired fibrinolysis of hypertensive patients. Kidney Blood Press Res. 2002;25(4):260-4. doi: 10.1159/000066348.
13 Pregnane X receptor mediates the induction of P-glycoprotein by spironolactone in HepG2 cells. Toxicology. 2011 Jul 11;285(1-2):18-24. doi: 10.1016/j.tox.2011.03.015. Epub 2011 Apr 1.
14 A Gene Expression Biomarker Identifies Chemical Modulators of Estrogen Receptor in an MCF-7 Microarray Compendium. Chem Res Toxicol. 2021 Feb 15;34(2):313-329. doi: 10.1021/acs.chemrestox.0c00243. Epub 2021 Jan 6.
15 Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study. Hypertension. 1980 Sep-Oct;2(5):672-9. doi: 10.1161/01.hyp.2.5.672.