期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 27, 期 13, 页码 2905-2913出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2019.05.021
关键词
Bruton's Tyrosine Kinase (BTK); Fragment screen; Computer aid drug design (CADD)
资金
- Biogen Inc.
- Sunesis Pharmaceuticals, Inc.
Since the approval of ibrutinib for the treatment of B-cell malignancies in 2012, numerous clinical trials have been reported using covalent inhibitors to target Bruton's tyrosine kinase (BTK) for oncology indications. However, a formidable challenge for the pharmaceutical industry has been the identification of reversible, selective, potent molecules for inhibition of BTK. Herein, we report application of Tethering-fragment-based screens to identify low molecular weight fragments which were further optimized to improve on-target potency and ADME properties leading to the discovery of reversible, selective, potent BTK inhibitors suitable for preclinical proof-of-concept studies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据