Valsartan
Valsartan is an angiotensin II (ATII) type 1 receptor (AT1) inhibitor that is clinically used to lower blood pressure and coronary resistance, and to decrease cardiac hypertrophy. Valsartan exhibits antihypertensive, cardioprotective, neuroprotective, anti-angiogenic, and anti-inflammatory activities. Inhibition of the ATII type 1 receptor results in inhibition of NF-κB and AP-1 activation. Valsartan induces autophagy through alteration of Akt/mTOR signaling in the rat heart, decreasing infarct size in an ischemia-reperfusion model. In neurons, valsartan promotes spinogenesis, increasing the number of AMPA receptors on the cell surface and altering levels of CaMKIIα and phospho-CDK5. In vivo, valsartan prevents induction of cardiotrophin-1, inhibiting increases in creatine kinase, atrial natriuretic peptide, and the heart weight/body weight ratio during heart failure. Additionally, inhibition of the angiotensin II type 1 (AT1) receptor prevents phosphorylation of Akt and decreases expression of VEGF in bone marrow stromal cells. Valsartan also inhibits release of pro-inflammatory cytokines such as IL-6, TNF-α, and IL-1β independent of its activity on ATII type 1 receptors.
References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/18978729
| Cas No. |
137862-53-4 |
|---|---|
| Purity |
≥98% |
| Formula |
C24H29N5O3 |
| Formula Wt. |
435.52 |
| Chemical Name |
N-(1-Oxopentyl)-N-[[2’-1H-tetrazol-5-yl)[1,1’-biphenyl]-4-yl]methyl]-L-valine |
| IUPAC Name |
(2S)-3-methyl-2-[pentanoyl-[[4-[2-(2H-tetrazol-5-yl)phenyl]phenyl]methyl]amino]butanoic acid |
| Melting Point |
116-117°C |
| Appearance |
White to off white powder |
Wu X, He L, Cai Y, et al. Induction of autophagy contributes to the myocardial protection of valsartan against ischemia reperfusion injury. Mol Med Rep. 2013 Dec;8(6):1824-30. PMID: 24084854.
Sohn YI, Lee NJ, Chung A, et al. Antihypertensive drug Valsartan promotes dendritic spine density by altering AMPA receptor trafficking. Biochem Biophys Res Commun. 2013 Oct 4;439(4):464-70. PMID: 24012668.
Cheng CI, Hsiao CC, Wu SC, et al. Valsartan impairs angiogenesis of mesenchymal stem cells through Akt pathway. Int J Cardiol. 2013 Sep 10;167(6):2765-74. PMID: 22805546.
Al-Mazroua HA, Al-Rasheed NM, Korashy HM. Downregulation of the cardiotrophin-1 gene expression by valsartan and spironolactone in hypertrophied heart rats in vivo and rat cardiomyocyte H9c2 cell line in vitro: a novel mechanism of cardioprotection. J Cardiovasc Pharmacol. 2013 Apr;61(4):337-44. PMID: 23288202.
Iwashita M, Sakoda H, Kushiyama A, et al. Valsartan, independently of AT1 receptor or PPARγ, suppresses LPS-induced macrophage activation and improves insulin resistance in cocultured adipocytes. Am J Physiol Endocrinol Metab. 2012 Feb 1;302(3):E286-96. PMID: 22045314.
Müller DN, Mervaala EM, Dechend R, et al. Angiotensin II (AT(1)) receptor blockade reduces vascular tissue factor in angiotensin II-induced cardiac vasculopathy. Am J Pathol. 2000 Jul;157(1):111-22. PMID: 10880382.
Izumi S, Nozaki Y, Maeda K, et al. Investigation of the impact of substrate selection on in vitro organic anion transporting polypeptide 1B1 inhibition profiles for the prediction of drug-drug interactions. Drug Metab Dispos. 2015 Feb;43(2):235-247. PMID: 25414411.
