开发针对守门突变激酶的“DFG-out”抑制剂。
Development of 'DFG-out' inhibitors of gatekeeper mutant kinases.
机构信息
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
出版信息
Bioorg Med Chem Lett. 2012 Aug 15;22(16):5297-302. doi: 10.1016/j.bmcl.2012.06.036. Epub 2012 Jun 23.
Abstract
HG-7-85-01(22) and HG-7-86-01(26) are thiazolo[5,4-b]pyridine containing type II tyrosine kinase inhibitors with potent cellular activity against both wild-type and 'gatekeeper' mutant T315I- Bcr-Abl. Here we report on the 'hybrid design' concept and subsequent structure activity guided optimization efforts that resulted in the development of these inhibitors.
摘要
HG-7-85-01(22) 和 HG-7-86-01(26) 是噻唑并[5,4-b]吡啶类的 II 型酪氨酸激酶抑制剂，对野生型和“守门员”突变 T315I-Bcr-Abl 均具有强大的细胞活性。在这里，我们报告了“混合设计”的概念以及随后的结构活性导向优化工作，这些工作导致了这些抑制剂的开发。
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