title: Potent and selective pyrazole-based inhibitors of B-Raf kinase.
abstract: Herein we describe a novel pyrazole-based class of ATP competitive B-Raf inhibitors. These inhibitors exhibit both excellent cellular potency and striking B-Raf selectivity. A subset of these inhibitors has demonstrated the ability to inhibit downstream ERK phosphorylation in LOX tumors from mouse xenograft studies.
authors.affiliation: Lead Optimization, Array BioPharma, 3200 Walnut Street, Boulder, CO 80301, USA. josh.hansen@arraybiopharma.com
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Hansen
authors.forename: Jonas
authors.initials: J
authors.lastname: Grina
authors.forename: Brad
authors.initials: B
authors.lastname: Newhouse
authors.forename: Mike
authors.initials: M
authors.lastname: Welch
authors.forename: George
authors.initials: G
authors.lastname: Topalov
authors.forename: Nicole
authors.initials: N
authors.lastname: Littman
authors.forename: Michele
authors.initials: M
authors.lastname: Callejo
authors.forename: Susan
authors.initials: S
authors.lastname: Gloor
authors.forename: Matthew
authors.initials: M
authors.lastname: Martinson
authors.forename: Ellen
authors.initials: E
authors.lastname: Laird
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Brandhuber
authors.forename: Guy
authors.initials: G
authors.lastname: Vigers
authors.forename: Tony
authors.initials: T
authors.lastname: Morales
authors.forename: Rich
authors.initials: R
authors.lastname: Woessner
authors.forename: Nikole
authors.initials: N
authors.lastname: Randolph
authors.forename: Joseph
authors.initials: J
authors.lastname: Lyssikatos
authors.forename: Alan
authors.initials: A
authors.lastname: Olivero
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D008956:Models, Chemical; D009368:Neoplasm Transplantation; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D011720:Pyrazoles / Q000737:chemistry*; D048490:raf Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D048493:Proto-Oncogene Proteins B-raf; D048490:raf Kinases