Portal de Periódicos da CAPES

Identification of a novel series of BET family bromodomain inhibitors: Binding mode and profile of I-BET151 (GSK1210151A)

2012; Elsevier BV; Volume: 22; Issue: 8 Linguagem: Inglês

10.1016/j.bmcl.2012.02.041

1464-3405

Jonathan T. Seal, Yann Lamotte, Frédéric Donche, Anne Bouillot, Olivier Mirguet, Françoise Gellibert, Edwige Nicodème, Gaël Krysa, Jorge Kirilovsky, Sören Beinke, Scott McCleary, Inma Rioja, Paul Bamborough, Chun‐wa Chung, Laurie Gordon, Toni Lewis, Ann L. Walker, Leanne Cutler, David Lugo, David M. Wilson, Jason Witherington, Kevin Lee, Rab K. Prinjha,

RNA Interference and Gene Delivery

A novel series of quinoline isoxazole BET family bromodomain inhibitors are discussed. Crystallography is used to illustrate binding modes and rationalize their SAR. One member, I-BET151 (GSK1210151A), shows good oral bioavailability in both the rat and minipig as well as demonstrating efficient suppression of bacterial induced inflammation and sepsis in a murine in vivo endotoxaemia model.