| Title : Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity - Zhou_2010_J.Med.Chem_53_7251 |
| Author(s) : Zhou C , Garcia-Calvo M , Pinto S , Lombardo M , Feng Z , Bender K , Pryor KD , Bhatt UR , Chabin RM , Geissler WM , Shen Z , Tong X , Zhang Z , Wong KK , Roy RS , Chapman KT , Yang L , Xiong Y |
| Ref : Journal of Medicinal Chemistry , 53 :7251 , 2010 |
|
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 IC(50) values of 1 and 2 nM and is not active (IC(50) > 25 microM) against a panel of closely related proteases. It has lower serum binding than its close analogues and is bioavailable in mouse. Subchronic dosing of 8o in PrCP(-/-) and WT mice at 100 mg/kg for 5 days resulted in a 5% reduction in body weight in WT mice and a 1% reduction in PrCP KO mice. |
| PubMedSearch : Zhou_2010_J.Med.Chem_53_7251 |
| PubMedID: 20857914 |
| Gene_locus related to this paper: human-PRCP |
| Inhibitor | UCI-80224067 |
| Gene_locus | human-PRCP |
Zhou C, Garcia-Calvo M, Pinto S, Lombardo M, Feng Z, Bender K, Pryor KD, Bhatt UR, Chabin RM, Geissler WM, Shen Z, Tong X, Zhang Z, Wong KK, Roy RS, Chapman KT, Yang L, Xiong Y (2010)
Design and synthesis of prolylcarboxypeptidase (PrCP) inhibitors to validate PrCP as a potential target for obesity
Journal of Medicinal Chemistry
53 :7251
Zhou C, Garcia-Calvo M, Pinto S, Lombardo M, Feng Z, Bender K, Pryor KD, Bhatt UR, Chabin RM, Geissler WM, Shen Z, Tong X, Zhang Z, Wong KK, Roy RS, Chapman KT, Yang L, Xiong Y (2010)
Journal of Medicinal Chemistry
53 :7251