155873-50-0Relevant articles and documents
Structure-based design of dipeptide derivatives for the human neutral endopeptidase
Misawa, Kensuke,Suzuki, Yasuto,Takahashi, Satoshi,Yoshimori, Atsushi,Takasawa, Ryoko,Shibuya, Yusuke,Tanuma, Sei-Ichi
experimental part, p. 5935 - 5947 (2011/11/04)
Neutral endopeptidase (NEP) plays a key role in the metabolic inactivation of various bioactive peptides such as atrial natriuretic peptide (ANP), endothelins, and enkephalins. Furthermore, NEP is known to work as elastase in skin fibroblast. Therefore, effective inhibitors of NEP offer significant therapeutic interest as antihypertensives, analgesics, and skin anti-aging agents. Recently, the X-ray crystal structure of human NEP complexed with phosphoramidon has been reported and provided insights into the active site specificity of NEP. Here, we designed new inhibitors by using in silico molecular modeling and synthesized them by short steps. Expectedly, we found highly effective inhibitors with sub-nanomolar levels of IC50 values. These results indicate that our structure-based molecular designing program is useful for obtaining novel NEP inhibitors. Furthermore, these inhibitors may be attractive leads for the generation of new pharmaceuticals for NEP-related diseases.
N-phosphonomethyl dipeptides and their phosphonate prodrugs, a new generation of neutral endopeptidase (NEP, EC 3.4.24.11) inhibitors
De Lombaert,Erion,Tan,Blanchard,El-Chehabi,Ghai,Sakane,Berry,Trapani
, p. 498 - 511 (2007/10/02)
Inhibitors of the zinc protease neutral endopeptidase (NEP, EC 3.4.24.11) offer significant therapeutic interest as antihypertensives due to their ability to potentiate the biological action of the circulating natriuretic hormone ANF (atrial natriuretic f
