De Lombaert S, Ghai R D, Jeng A Y, Trapani A J, Webb R L
Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
Biochem Biophys Res Commun. 1994 Oct 14;204(1):407-12. doi: 10.1006/bbrc.1994.2473.
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.
CGS 26303是一种强效且结构独特的中性内肽酶（NEP）非肽类抑制剂，能够保护心房利钠肽（ANP）不被酶解。此外，CGS 26303在体外表现出适度的内皮素转化酶（ECE）抑制活性。与强效但选择性的NEP抑制剂CGS 24592不同，CGS 26303在外源性给予大内皮素-1（big ET-1）后能显著阻断大鼠体内内皮素-1的产生，并在长期给药期间降低自发性高血压大鼠的平均动脉压。这些结果表明，CGS 26303代表了一类新型治疗药物，对治疗心血管和肾脏疾病可能具有益处。
