1. Academic Validation
  2. Identification of a novel series of BET family bromodomain inhibitors: binding mode and profile of I-BET151 (GSK1210151A)

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

  • Bioorg Med Chem Lett. 2012 Apr 15;22(8):2968-72. doi: 10.1016/j.bmcl.2012.02.041.
Jonathan Seal 1 Yann Lamotte Frédéric Donche Anne Bouillot Olivier Mirguet Françoise Gellibert Edwige Nicodeme Gael Krysa Jorge Kirilovsky Soren 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
Affiliations

Affiliation

  • 1 Epinova DPU, GlaxoSmithKline R&D, Medicines Research Centre, Stevenage, Hertfordshire, UK. jon.t.seal@gsk.com
Abstract

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.

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