2. Academic Validation
  3. Synthesis and biological evaluation of novel benzamide derivatives as potent smoothened antagonists

Synthesis and biological evaluation of novel benzamide derivatives as potent smoothened antagonists

  • Bioorg Med Chem Lett. 2014 Mar 1;24(5):1426-31. doi: 10.1016/j.bmcl.2014.01.006.
Tian-Ming Wu 1,  Dao-Cai Wang 2,  Pu Xiang 1,  Jian-Nan Zhang 1,  Ya-Xiong Sang 1,  Hong-Jun Lin 1,  Jie Chen 1,  Gang Xie 1,  Hang Song 2,  Ying-Lan Zhao 3,  Yong-Mei Xie 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China.
  • 2 Department of Pharmaceutical and Biological Engineering, College of Chemical Engineering, Sichuan University, Chengdu 610065, China.
  • 3 State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: zhaoyinglan@scu.edu.cn.
  • 4 State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China. Electronic address: xieym@scu.edu.cn.
PMID: 24491459 DOI: 10.1016/j.bmcl.2014.01.006
Abstract

A series of novel benzamide derivatives were prepared and evaluated using cell-based measurements. Among these compounds, 10f significantly inhibited Hedgehog signaling and showed equivalent or more potency than GDC-0449 in different tests. Furthermore, compound 10f potently inhibited the proliferation of Daoy, a medulloblastoma cell line that is reported to be resistant to GDC-0449, which indicated a promising prospect in the treatment of Hedgehog signaling pathway related Cancer in clinical trial.

Keywords

Amide derivatives; Hedgehog; Smoothened antagonist.

Figures