title: Conformation-specific inhibitors of Raf kinases.
abstract: Since the discovery linking B-Raf mutations to human tumors in 2002, significant advances in the development of Raf inhibitors have been made, leading to the recent approval of two Raf inhibitor drugs. This chapter includes a brief introduction to B-Raf as a validated target and focuses on the three different binding modes observed with Raf small-molecule inhibitors. These various binding modes lock the Raf kinase in different conformations that impact the toxicity profiles of the inhibitors. Possible solutions to mitigate the side effects caused by inhibitor-induced dimerization are also discussed.
authors.affiliation: Takeda California, San Diego, California, USA. Electronic address: xxw104@gmail.com.
authors.forename: Xiaolun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Takeda California, San Diego, California, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Schleicher
mesh_terms: D000818:Animals; D006801:Humans; D011487:Protein Conformation / Q000187:drug effects*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D048490:raf Kinases / Q000037:antagonists & inhibitors*
chemical_list: D047428:Protein Kinase Inhibitors; D048490:raf Kinases
keywords: Active; Conformation; Inactive; Inhibitors; Kinase; Raf