A thiocarbamate inhibitor of endothelial lipase raises HDL cholesterol levels in mice
作者:M.N. Greco、M.A. Connelly、G.C. Leo、M.W. Olson、E. Powell、Z. Huang、M. Hawkins、C. Smith、C. Schalk-Hihi、A.L. Darrow、H. Xin、W. Lang、B.P. Damiano、D.J. Hlasta
DOI:10.1016/j.bmcl.2013.02.113
日期:2013.5
By screening directed libraries of serine hydrolase inhibitors using the cell surface form of endothelial lipase (EL), we identified a series of carbamate-derived (EL) inhibitors. Compound 3 raised plasma HDL-C levels in the mouse, and a correlation was found between HDL-C and plasma compound levels. Spectroscopic and kinetic studies support a covalent mechanism of inhibition. Our findings represent the first report of EL inhibition as an effective means for increasing HDL-C in an in vivo model. (C) 2013 Elsevier Ltd. All rights reserved.