Discovery of EBI-907: A highly potent and orally active B-Raf(V600E) inhibitor for the treatment of melanoma and associated cancers

  • Bioorg Med Chem Lett. 2016 Feb 1;26(3):819-823. doi: 10.1016/j.bmcl.2015.12.086.
Biao Lu  1 ,  Hu Cao  1 ,  Jingsong Cao  2 ,  Song Huang  1 ,  Qiyue Hu  1 ,  Dong Liu  2 ,  Ru Shen  2 ,  Xiaodong Shen  1 ,  Weikang Tao  1 ,  Hong Wan  1 ,  Dan Wang  1 ,  Yinfa Yan  2 ,  Liuqing Yang  2 ,  Jiayin Zhang  2 ,  Lei Zhang  1 ,  Lianshan Zhang  3 ,  Minsheng Zhang  2
Affiliations
  • 1. Shanghai Hengrui Pharmaceutical Co., Ltd, 279 Wenjing Rd, Minhang Hi-tech Zone, Shanghai 200245, China.
  • 2. Eternity Bioscience Inc., 2005 EastPark Blvd, Cranbury, NJ 08512, USA.
  • 3. National Engineering and Research Center for Targeted Drugs, Jiangsu Hengrui Medicine Co., Ltd, 7 Kunlun Shan Road, Lianyungang Economic and Technology Development Zone, Jiangsu Province, China.
PMID: 26739779 DOI: 10.1016/j.bmcl.2015.12.086
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 compounds EBI-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.

Keywords
B-Raf(V600E); Cancer; Kinase; Pyrazolo[3,4-c]isoquinoline; Scaffold hopping.
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-117707
    EBI-907
    B-RafV600E Inhibitor
    target: Raf
    Research Areas: Cancer