title: The genesis of Zelboraf: targeting mutant B-Raf in melanoma.
abstract: The protein kinase B-Raf is a critical component of the Ras/MAPK signaling pathway. An oncogenic B-Raf mutation that constitutively activates the kinase was identified in ~50% of melanoma patients and in other cancers. A structure-guided drug discovery approach enabled the development of Zelboraf, a targeted inhibitor of oncogenic B-Raf. This drug has been used successfully in the clinic to treat metastatic melanoma patients harboring B-Raf mutations.
authors.affiliation: Department of Pharmacology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Davis
authors.forename: Joseph
authors.initials: J
authors.lastname: Schlessinger
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000009:adverse effects / Q000494:pharmacology*; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; D048493:Proto-Oncogene Proteins B-raf