Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice

  • Bioorg Med Chem. 2013 Dec 15;21(24):7724-34. doi: 10.1016/j.bmc.2013.10.023.
Shaoyi Sun  1 ,  Richard Dean ,  Qi Jia ,  Alla Zenova ,  Jing Zhong ,  Celene Grayson ,  Clark Xie ,  Andrea Lindgren ,  Pritpaul Samra ,  Luis Sojo ,  Margaret van Heek ,  Linus Lin ,  David Percival ,  Jian-Min Fu ,  Michael D Winther ,  Zaihui Zhang
Affiliations
  • 1. Xenon Pharmaceuticals Inc, 200-3650 Gilmore Way, Burnaby, BC V5G 4W8, Canada. Electronic address: [email protected].
PMID: 24211162 DOI: 10.1016/j.bmc.2013.10.023
Abstract

Endothelial Lipase (EL) activity has been implicated in HDL metabolism and in atherosclerotic plaque development; inhibitors are proposed to be efficacious in the treatment of dyslipidemia related Cardiovascular Disease. We describe here the discovery of a novel class of anthranilic acids EL inhibitors. XEN445 (compound 13) was identified as a potent and selective EL inhibitor, that showed good ADME and PK properties, and demonstrated in vivo efficacy in raising plasma HDLc concentrations in mice.

Keywords
Anthranilic acid; Cardiovascular disease; Endothelial lipase inhibitors; HDL cholesterol.
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