Potent and selective inhibitors of human reticulocyte 12/15-lipoxygenase as anti-stroke therapies

…, V Kenyon, A Jadhav, A Simeonov, EH Lo…

Index: Rai, Ganesha; Joshi, Netra; Jung, Joo Eun; Liu, Yu; Schultz, Lena; Yasgar, Adam; Perry, Steve; Diaz, Giovanni; Zhang, Qiangli; Kenyon, Victor; Jadhav, Ajit; Simeonov, Anton; Lo, Eng H.; Van Leyen, Klaus; Maloney, David J.; Holman, Theodore R. Journal of Medicinal Chemistry, 2014 , vol. 57, # 10 p. 4035 - 4048

Full Text: HTML

Citation Number: 21

Abstract

A key challenge facing drug discovery today is variability of the drug target between species, such as with 12/15-lipoxygenase (12/15-LOX), which contributes to ischemic brain injury, but its human and rodent isozymes have different inhibitor specificities. In the current work, we have utilized a quantitative high-throughput (qHTS) screen to identify compound 1 (ML351), a novel chemotype for 12/15-LOX inhibition that has nanomolar potency (IC50= 200 nM) ...