Hui-Fang Li, Yadong Chen, Sha-Sha Rao, Xiu-Mei Chen, Hai-Chun Liu, Ji-Hong Qin, Wei-Fang Tang, Yue-Wang, Xiang Zhou and Tao Lu Pages 1618 - 1634 ( 17 )
Oncogenic B-Raf has been identified in a variety of cancers with high incidence, especially in malignant melanoma and thyroid cancer. Most B-Raf mutations elicit elevated kinase activity and the constitutive activation of Ras/Raf/MEK/ERK pathway, which induces proliferation and promotes malignant transformation. Therefore, B-Raf inhibitors, targeting B-Raf or mutated B-Raf, have received increasing momentum in oncology drug discovery arena. This review focuses on the diverse small-molecule inhibitors of B-Raf kinase recently reported in the literature, including those currently in clinical and preclinical phase. They are described as two categories, type I or type II kinase inhibitors, based on their different mechanism of action with active or inactive conformations of the B-Raf kinase derived from the available crystal structures or molecular docking analysis. A particular emphasis is placed on their binding modes and the structure-activity relationship (SAR) of each chemical structure class.
B-Raf,B-RafV600E,B-Raf kinase inhibitors,binding mode,SAR,mechanism of action
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