Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity

…, M Garcia-Calvo, S Pinto, M Lombardo…

Index: Zhou, Changyou; Garcia-Calvo, Margareta; Pinto, Shirly; Lombardo, Matthew; Feng, Zhe; Bender, Kate; Pryor, Kellyann D.; Bhatt, Urmi R.; Chabin, Renee M.; Geissler, Wayne M.; Shen, Zhu; Tong, Xinchun; Zhang, Zhoupeng; Wong, Kenny K.; Roy, Ranabir Sinha; Chapman, Kevin T.; Yang, Lihu; Xiong, Yusheng Journal of Medicinal Chemistry, 2010 , vol. 53, # 19 p. 7251 - 7263

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Citation Number: 38

Abstract

Prolylcarboxypeptidase (PrCP) is a serine protease that may have a role in metabolism regulation. A class of reversible, potent, and selective PrCP inhibitors was developed starting from a mechanism based design for inhibiting this serine protease. Compound 8o inhibits human and mouse PrCP at IC50 values of 1 and 2 nM and is not active (IC50> 25 μM) against a panel of closely related proteases. It has lower serum binding than its close ...