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Abstract
Grant Number: 1R43HL074676-01 PI Name: LARRICK, JAMES W. PI Email: calvarez@pano.com PI Title: PRESIDENT AND SCIENTIFIC DIRECTOR Project Title: An Endogenous Cardioprotectant Abstract: DESCRIPTION (provided by applicant): Des-asp angiotensin 1 (DAA-1) is a potent endogenous cardiovasculo-protective peptide generated from angiotensin 1 by a novel aminopeptidase. DAA-1 given both iv and po has sub-micromolar protective activity in a number of cardiac and renal pathophysiology. These activities are mediated by a unique angiotensin 1 receptor subtype. Based on the novel proprietary activities of DAA-1 and its limited toxicity, the overall goal of the present project is to expand the preclinical studies of DAA-1 to support submission of an IND. Clinical need and preclinical animal studies of DAA-1 support its initial use in the context of myocardial infarction-reperfusion injury. In Phase I the activity of DAA-1 will be compared to ACE inhibition and ARB drugs using a rat cardiac reperfusion model. This will be followed by a comparison of the drugs versus DAA-1 in a porcine cardiac reperfusion model. Phase II goals include preparation of GMP grade DAA-1, expansion of preclinical toxicology studies, and validation of assays of DAA-1 in preparation for submission of an IND application. Because DAA-1 binds a novel, validated target, this molecule is expected to have significant therapeutic potential in cardiovascular medicine.
Thesaurus Terms:
angiotensin, cardiovascular agent, drug design /synthesis /production, myocardial infarction, protective chemical group
ACE inhibitor, angiotensin receptor, disease /disorder model, enzyme inhibitor, peptide, receptor binding, renin angiotensin system, reperfusion
blood chemistry, echocardiography, immunocytochemistry, immunofluorescence technique, laboratory rat, swine, terminal nick end labeling, western blotting
Institution: PANORAMA RESEARCH, INC. 2462 WYANDOTTE ST MOUNTAIN VIEW, CA 94043 Fiscal Year: 2003 Department: Project Start: 29-SEP-2003 Project End: 28-MAR-2004 ICD: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE IRG: ZRG1