Details of the Drug Combination

General Information of Drug Combination (ID: DC0X15D)

Drug Combination Name
Chlorthalidone Spironolactone
Indication
Disease Entry Status REF
Renal Insufficiency Phase 2 [1]
Component Drugs Chlorthalidone   DM4DMBT Spironolactone   DM2AQ5N
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Chlorthalidone
Disease Entry ICD 11 Status REF
Edema MG29 Approved [2]
Hypertension BA00-BA04 Approved [2]
High blood pressure BA00 Investigative [3]
Chlorthalidone Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Solute carrier family 12 member 1 (SLC12A1) TTS087L S12A1_HUMAN Blocker [7]
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Chlorthalidone Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Increases Activity [8]
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Indication(s) of Spironolactone
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [4]
Congestive heart failure BD10 Approved [5]
Edema MG29 Approved [4]
Hyperaldosteronism 5A72 Approved [4]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [6]
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 ClinicalTrials.gov (NCT05222191) Spironolactone in CKD Enabled by Chlorthalidone: PILOT
2 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: 7147).
3 Chlorthalidone FDA Label
4 Spironolactone FDA Label
5 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).
6 Spironolactone in Covid-19 Induced ARDS
7 The 45-year story of the development of an anti-aldosterone more specific than spironolactone. Mol Cell Endocrinol. 2004 Mar 31;217(1-2):45-52.
8 Detection of low-renin hypertension; evaluation of out-patient renin-stimulating methods. Clin Sci Mol Med. 1975 Feb;48(2):91-6. doi: 10.1042/cs0480091.
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.