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CGEN-856 & CGEN-857
Using a new computational method aimed at discovering novel GPCR ligands encrypted in the human proteome (Shemesh et al. 2008), Compugen has discovered two new peptide ligands of the Mas GPCR receptor, one of the key components of the renin angiotensin (RAS) system. These novel peptides, CGEN-856 and CGEN-857, were discovered amongst a group of selected peptides screened for activation of 152 selected GPCRs using a calcium flux assay. CGEN-856 and CGEN-857 induce calcium flux in Mas-transfected cells, in a dose-dependent manner. Neither has significant homology to any of the known GPCR ligands or to one another. The peptides displayed activity in various studies, and were shown to have cardio-protective effects in-vivo.
In-particular, CGEN-856 induced relaxation of rat and murine aorta in an NO- and Mas-dependent manner, reduced in-vivo cardiac remodeling induced by isoproterenol or ischemia, displayed anti-hypertensive effects as well as cardiac and renal anti-fibrotic effects. This peptide may thus be a useful therapeutic agent in conditions benefiting from an increase in the activity of the Mas receptor, such as hypertension, heart failure, cardiac remodeling, myocardial infarction, renal fibrosis and other cardiovascular pathologies. |
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