2. Academic Validation
  3. 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. [email protected]
PMID: 22437115 DOI: 10.1016/j.bmcl.2012.02.041
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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