title: Discovery of Small Molecule RIP1 Kinase Inhibitors for the Treatment of Pathologies Associated with Necroptosis.
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.
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Harris
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Deepak
authors.initials: D
authors.lastname: Bandyopadhyay
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Scott B
authors.initials: SB
authors.lastname: Berger
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Nino
authors.initials: N
authors.lastname: Campobasso
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Capriotti
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Cox
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Lauren
authors.initials: L
authors.lastname: Dare
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Finger
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Hoffman
authors.affiliation: Platform Technology & Science, GlaxoSmithKline , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Kirsten M
authors.initials: KM
authors.lastname: Kahler
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Ruth
authors.initials: R
authors.lastname: Lehr
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: John D
authors.initials: JD
authors.lastname: Lich
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Nagilla
authors.affiliation: Platform Technology & Science, GlaxoSmithKline , Research Triangle Park, North Carolina 27709, United States.
authors.forename: Robert T
authors.initials: RT
authors.lastname: Nolte
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Michael T
authors.initials: MT
authors.lastname: Ouellette
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Christina S
authors.initials: CS
authors.lastname: Pao
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Michelle C
authors.initials: MC
authors.lastname: Schaeffer
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Angela
authors.initials: A
authors.lastname: Smallwood
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Helen H
authors.initials: HH
authors.lastname: Sun
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Swift
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Totoritis
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Paris
authors.initials: P
authors.lastname: Ward
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Marquis
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: John
authors.initials: J
authors.lastname: Bertin
authors.affiliation: Pattern Recognition Receptor DPU and Platform Technology & Science, GlaxoSmithKline , Collegeville Road, Collegeville, Pennsylvania 19426, United States.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Gough
keywords: RIP1; necroptosis; type II kinase inhibitors