Details of the Drug Combination

General Information of Drug Combination (ID: DC5AOCT)

Drug Combination Name
Chlorthalidone Amlodipine
Indication
Disease Entry Status REF
Hypertension Phase 1 [1]
Component Drugs Chlorthalidone   DM4DMBT Amlodipine   DMBDAZV
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 [6]
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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 [7]
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Indication(s) of Amlodipine
Disease Entry ICD 11 Status REF
Angina pectoris BA40 Approved [4]
Chronic heart failure BD1Z Approved [4]
Hypertension BA00-BA04 Approved [5]
Malignant essential hypertension BA00 Approved [4]
Stroke 8B20 Investigative [4]
Amlodipine Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Voltage-gated calcium channel alpha-2/delta-1 (CACNA2D1) TTFK1JQ CA2D1_HUMAN Blocker [8]
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Amlodipine Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [9]
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Amlodipine Interacts with 7 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Tyrosine-protein kinase JAK2 (JAK2) OTBIDOOR JAK2_HUMAN Increases Expression [10]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Response To Substance [11]
Platelet basic protein (PPBP) OT1FHGQS CXCL7_HUMAN Decreases Expression [12]
Retinoblastoma-associated protein (RB1) OTQJUJMZ RB_HUMAN Decreases Phosphorylation [13]
Cyclin-dependent kinase inhibitor 1 (CDKN1A) OTQWHCZE CDN1A_HUMAN Increases Expression [13]
Resistin (RETN) OTW5Z1NH RETN_HUMAN Decreases Expression [14]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Increases ADR [15]
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⏷ Show the Full List of 7 DOT(s)

Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Hypertension DCPZY7H N. A. Phase 1 [16]
Hypertension DCFUKT5 N. A. Phase 1 [17]
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References

1 ClinicalTrials.gov (NCT02152969) Drug-drug Interaction Study (Telmisartan, Amlodipine, Chlorthalidone)
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 Amlodipine 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: 6981).
6 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.
7 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.
8 A first drug combination for the treatment of arterial hypertension with a calcium channel antagonist (amlodipine besylate) and an angiotensin receptor blocker (valsartan): Exforge. Rev Med Liege. 2007 Nov;62(11):688-94.
9 Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab Dispos. 2014 Feb;42(2):245-9.
10 Amlodipine inhibits cell proliferation via PKD1-related pathway. Biochem Biophys Res Commun. 2008 May 2;369(2):376-81. doi: 10.1016/j.bbrc.2008.02.075. Epub 2008 Feb 25.
11 Effects of amlodipine on TGF--induced Smad2, 4 expressions in adriamycin toxicity of rat mesangial cells. Arch Toxicol. 2011 Jun;85(6):663-8. doi: 10.1007/s00204-011-0667-4. Epub 2011 Feb 20.
12 Platelet morphology and plasma indices of platelet activation in essential hypertension: effects of amlodipine-based antihypertensive therapy. Ann Med. 2004;36(7):552-7. doi: 10.1080/07853890410017386.
13 G1 cell cycle arrest by amlodipine, a dihydropyridine Ca2+ channel blocker, in human epidermoid carcinoma A431 cells. Biochem Pharmacol. 2007 Apr 1;73(7):943-53. doi: 10.1016/j.bcp.2006.12.011. Epub 2006 Dec 14.
14 Amlodipine improves endothelial function and metabolic parameters in patients with hypertension. Int J Cardiol. 2009 Mar 20;133(1):23-31. doi: 10.1016/j.ijcard.2007.11.058. Epub 2008 Jan 15.
15 Pharmacogenetic association of the NPPA T2238C genetic variant with cardiovascular disease outcomes in patients with hypertension. JAMA. 2008 Jan 23;299(3):296-307. doi: 10.1001/jama.299.3.296.
16 ClinicalTrials.gov (NCT02121041) Ambulatory vs Office BP Management Usual Care for Diagnosing and Managing Hypertension: A Pilot Study
17 ClinicalTrials.gov (NCT05976438) Skin Sodium and Salt Sensitivity of Blood Pressure