2. Academic Validation
  3. Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis

Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis

  • ACS Med Chem Lett. 2013 Nov 4;4(12):1238-43. doi: 10.1021/ml400382p.
Philip A Harris 1,  Deepak Bandyopadhyay 1,  Scott B Berger 1,  Nino Campobasso 1,  Carol A Capriotti 1,  Julie A Cox 1,  Lauren Dare 1,  Joshua N Finger 1,  Sandra J Hoffman 1,  Kirsten M Kahler 2,  Ruth Lehr 1,  John D Lich 1,  Rakesh Nagilla 1,  Robert T Nolte 2,  Michael T Ouellette 1,  Christina S Pao 1,  Michelle C Schaeffer 1,  Angela Smallwood 1,  Helen H Sun 1,  Barbara A Swift 1,  Rachel D Totoritis 1,  Paris Ward 1,  Robert W Marquis 1,  John Bertin 1,  Peter J Gough 1
Affiliations

Affiliations

  • 1 Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
  • 2 Platform Technology & Science, GlaxoSmithKline , Research Triangle Park, North Carolina 27709, United States.
PMID: 24900635 DOI: 10.1021/ml400382p
Abstract

Potent inhibitors of RIP1 kinase from three distinct series, 1-aminoisoquinolines, pyrrolo[2,3-b]pyridines, and furo[2,3-d]pyrimidines, all of the type II class recognizing a DLG-out inactive conformation, were identified from screening of our in-house kinase focused sets. An exemplar from the furo[2,3-d]pyrimidine series showed a dose proportional response in protection from hypothermia in a mouse model of TNFα induced lethal shock.

Keywords

RIP1; necroptosis; type II kinase inhibitors.

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