Discovery of EBI-907: A highly potent and orally active B-RafV600E inhibitor for the treatment of melanoma and associated cancers. Issue 3 (1st February 2016)

• Record Type: Journal Article
• Authors: Lu, Biao; Cao, Hu; Cao, Jingsong; Huang, Song; Hu, Qiyue; Liu, Dong; Shen, Ru; Shen, Xiaodong; Tao, Weikang; Wan, Hong; Wang, Dan; Yan, Yinfa; Yang, Liuqing; Zhang, Jiayin; Zhang, Lei; Zhang, Lianshan; Zhang, Minsheng
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 3(2016)
• Page Start: 819
• Page End: 823
• Publication Date: 2016-02-01
• Subjects: B-RafV600E -- Kinase -- Pyrazolo[3, 4-c]isoquinoline -- Scaffold hopping -- Cancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.12.086
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: A novel series of pyrazolo[3, 4- c ]isoquinoline derivatives was discovered as B-Raf V600E inhibitors through scaffold hopping based on a literature lead PLX4720. Further SAR exploration and optimization led to the discovery of potent B-Raf V600E inhibitors with good oral bioavailability in rats and dogs. One of the compoundsEBI-907 (13g ) demonstrated excellent in vivo efficacy in B-Raf V600E dependent Colo-205 tumor xenograft models in mouse and is under preclinical studies for the treatment of melanoma and B-Raf V600E associated cancers.