General Information of Drug Combination (ID: DC2V7NE)

Drug Combination Name
Valsartan Probucol
Indication
Disease Entry Status REF
Type 2 Diabetes Mellitus Phase 1 [1]
Component Drugs Valsartan   DMREUQ6 Probucol   DMVZQ2M
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 Valsartan
Disease Entry ICD 11 Status REF
Chronic heart failure BD1Z Approved [2]
Hypertension BA00-BA04 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Nephropathy GC2Z Investigative [2]
Valsartan Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Angiotensin II receptor type-1 (AGTR1) TT8DBY3 AGTR1_HUMAN Antagonist [8]
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Valsartan 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 [9]
Organic anion transporting polypeptide 1B1 (SLCO1B1) DT3D8F0 SO1B1_HUMAN Substrate [10]
Peptide transporter 1 (SLC15A1) DT9G7XN S15A1_HUMAN Substrate [11]
Organic anion transporter 3 (SLC22A8) DTVP67E S22A8_HUMAN Substrate [12]
Organic anion transporting polypeptide 1B3 (SLCO1B3) DT9C1TS SO1B3_HUMAN Substrate [9]
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Valsartan Interacts with 1 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Metabolism [13]
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Valsartan Interacts with 17 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Organic anion transporter 3 (SLC22A8) OT8BY933 S22A8_HUMAN Increases Expression [14]
Angiotensinogen (AGT) OTBZLYR3 ANGT_HUMAN Increases Expression [15]
Transforming growth factor beta-1 proprotein (TGFB1) OTV5XHVH TGFB1_HUMAN Decreases Expression [16]
Serum amyloid P-component (APCS) OT76JZ8Z SAMP_HUMAN Decreases Expression [17]
Albumin (ALB) OTVMM513 ALBU_HUMAN Decreases Export [18]
Angiogenin (ANG) OT3ECS6P ANGI_HUMAN Decreases Expression [7]
Fatty acid-binding protein, adipocyte (FABP4) OT3DKFOU FABP4_HUMAN Decreases Expression [7]
Natriuretic peptides B (NPPB) OTSN2IPY ANFB_HUMAN Decreases Expression [19]
Macrophage mannose receptor 1 (MRC1) OTTVCOPT MRC1_HUMAN Decreases Expression [7]
Cathepsin S (CTSS) OT3PXIPM CATS_HUMAN Decreases Expression [7]
Hematopoietic progenitor cell antigen CD34 (CD34) OT1MOFLZ CD34_HUMAN Decreases Expression [7]
Macrosialin (CD68) OTOYEY3J CD68_HUMAN Decreases Expression [7]
Peroxisome proliferator-activated receptor gamma (PPARG) OTHMARHO PPARG_HUMAN Decreases Expression [7]
CCAAT/enhancer-binding protein alpha (CEBPA) OTOM9OE4 CEBPA_HUMAN Decreases Expression [7]
Coxsackievirus and adenovirus receptor (CXADR) OT9ZP02A CXAR_HUMAN Decreases Expression [20]
Scavenger receptor cysteine-rich type 1 protein M130 (CD163) OT2E32LN C163A_HUMAN Decreases Expression [7]
Cytochrome P450 3A5 (CYP3A5) OTSXFBXB CP3A5_HUMAN Affects Response To Substance [21]
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⏷ Show the Full List of 17 DOT(s)
Indication(s) of Probucol
Disease Entry ICD 11 Status REF
Coronary artery disease BA80 Approved [5]
Coronary heart disease BA80.Z Approved [6]
Hypercholesterolaemia 5C80.0 Approved [6]
Hyperlipidemia 5C80.Z Approved [6]
Probucol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
ATP-binding cassette transporter A1 (ABCA1) TTJW1GN ABCA1_HUMAN Modulator [22]
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Probucol Interacts with 1 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Potassium voltage-gated channel subfamily H member 2 (KCNH2) OTZX881H KCNH2_HUMAN Decreases Activity [23]
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Test Results of This Drug Combination in Other Disease Systems

Indication DrugCom ID Cell Line Status REF
Glomerulonephritis DCLFY1P N. A. Phase 1 [24]
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References

1 ClinicalTrials.gov (NCT00655330) Probucol Combined With Valsartan in Reducing Proteinuria in Diabetes Nephropathy
2 Valsartan 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: 3937).
4 Valsartan for Prevention of Acute Respiratory Distress Syndrome in Hospitalized Patients With SARS-COV-2 (COVID-19) Infection Disease
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: 7277).
6 Probucol FDA Label
7 Valsartan improves adipose tissue function in humans with impaired glucose metabolism: a randomized placebo-controlled double-blind trial. PLoS One. 2012;7(6):e39930. doi: 10.1371/journal.pone.0039930. Epub 2012 Jun 29.
8 Radioligand binding assays: application of [(125)I]angiotensin II receptor binding. Methods Mol Biol. 2009;552:131-41.
9 Involvement of transporters in the hepatic uptake and biliary excretion of valsartan, a selective antagonist of the angiotensin II AT1-receptor, in humans. Drug Metab Dispos. 2006 Jul;34(7):1247-54.
10 Regulation of Organic Anion Transporting Polypeptides (OATP) 1B1- and OATP1B3-Mediated Transport: An Updated Review in the Context of OATP-Mediated Drug-Drug Interactions. Int J Mol Sci. 2018 Mar 14;19(3). pii: E855.
11 High-affinity interaction of sartans with H+/peptide transporters. Drug Metab Dispos. 2009 Jan;37(1):143-9.
12 Prediction of the overall renal tubular secretion and hepatic clearance of anionic drugs and a renal drug-drug interaction involving organic anion transporter 3 in humans by in vitro uptake experiments. Drug Metab Dispos. 2011 Jun;39(6):1031-8.
13 In vitro inhibition screening of human hepatic P450 enzymes by five angiotensin-II receptor antagonists. Eur J Clin Pharmacol. 2000 May;56(2):135-40.
14 Uric acid accumulation in the kidney triggers mast cell degranulation and aggravates renal oxidative stress. Toxicology. 2023 Jan 1;483:153387. doi: 10.1016/j.tox.2022.153387. Epub 2022 Dec 1.
15 Angiotensin II receptor blockade in normotensive subjects: A direct comparison of three AT1 receptor antagonists. Hypertension. 1999 Mar;33(3):850-5. doi: 10.1161/01.hyp.33.3.850.
16 [The relationship between the gene polymorphism of TGF-beta1 and early renal injury in patients with essential hypertension, and the effect of the gene polymorphism of TGF- beta1 on the individual treatment with valsartan]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2007 Aug;24(4):428-31.
17 C-reactive protein in heart failure: prognostic value and the effect of valsartan. Circulation. 2005 Sep 6;112(10):1428-34. doi: 10.1161/CIRCULATIONAHA.104.508465. Epub 2005 Aug 29.
18 Is renoprotection by angiotensin receptor blocker dependent on blood pressure?: the Saitama Medical School, Albuminuria Reduction in Diabetics with Valsartan (STAR) study. Hypertens Res. 2007 Jun;30(6):529-33. doi: 10.1291/hypres.30.529.
19 Effects of valsartan on circulating brain natriuretic peptide and norepinephrine in symptomatic chronic heart failure: the Valsartan Heart Failure Trial (Val-HeFT). Circulation. 2002 Nov 5;106(19):2454-8. doi: 10.1161/01.cir.0000036747.68104.ac.
20 Antiviral effect of Bosentan and Valsartan during coxsackievirus B3 infection of human endothelial cells. J Gen Virol. 2010 Aug;91(Pt 8):1959-1970. doi: 10.1099/vir.0.020065-0. Epub 2010 Apr 14.
21 Comparing antihypertensive effect and plasma ciclosporin concentration between amlodipine and valsartan regimens in hypertensive renal transplant patients receiving ciclosporin therapy. Am J Cardiovasc Drugs. 2011 Dec 1;11(6):401-9. doi: 10.2165/11593800-000000000-00000.
22 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
23 Probucol aggravates long QT syndrome associated with a novel missense mutation M124T in the N-terminus of HERG. Clin Sci (Lond). 2004 Aug;107(2):175-82. doi: 10.1042/CS20030351.
24 ClinicalTrials.gov (NCT00426348) A Study of the Antioxidant Probucol Combined With Valsartan in Patients With IgA Nephropathy