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

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

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.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-117707
    B-RafV600E Inhibitor.
    Raf