Recent Advances in the Research and Development of B-Raf Inhibitors

Title: Recent Advances in the Research and Development of B-Raf Inhibitors

Volume: 17 Issue: 16

Author(s): 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

Affiliation:

Keywords: B-Raf, B-RafV600E, B-Raf kinase inhibitors, binding mode, SAR, mechanism of action

Abstract: 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.

Cite this article as:

Li Hui-Fang, Chen Yadong, Rao Sha-Sha, Chen Xiu-Mei, Liu Hai-Chun, Qin Ji-Hong, Tang Wei-Fang, Yue-Wang , Zhou Xiang and Lu Tao, Recent Advances in the Research and Development of B-Raf Inhibitors, Current Medicinal Chemistry 2010; 17 (16) . https://dx.doi.org/10.2174/092986710791111242