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ID: ALA2380223

Journal: Bioorg Med Chem Lett

Title: A thiocarbamate inhibitor of endothelial lipase raises HDL cholesterol levels in mice.

Authors: Greco MN, Connelly MA, Leo GC, Olson MW, Powell E, Huang Z, Hawkins M, Smith C, Schalk-Hihi C, Darrow AL, Xin H, Lang W, Damiano BP, Hlasta DJ.

Abstract: 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.

CiteXplore: 23528297

DOI: 10.1016/j.bmcl.2013.02.113