2. Academic Validation
  3. Discovery of XEN445: a potent and selective endothelial lipase inhibitor raises plasma HDL-cholesterol concentration in mice

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

Affiliation

  • 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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