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Pharmacological Profile of a Non-peptidic Dual Inhibitor of Neutral Endopeptidase 24.11 and Endothelin-Converting Enzyme

https://doi.org/10.1006/bbrc.1994.2473Get rights and content

Abstract

CGS 26303 is a potent and structurally unique non-peptidic inhibitor of neutral endopeptidase (NEP) capable of protecting atrial natriuretic peptide (ANP) from enzymatic degradation. In addition, CGS 26303 displays modest endothelin-converting enzyme (ECE) inhibitory activity in vitro. Unlike CGS 24592, a potent but selective NEP inhibitor, CGS 26303 significantly blocks endothelin-1 production in rats after exogenous administration of big ET-1 and reduces the mean arterial pressure in spontaneously hypertensive rats during chronic administration. These results suggest that CGS 26303 represents a new class of therapeutic agents with potential benefits for the treatment of cardiovascular and renal disorders.

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