In Silico HTS and Structure Based Optimization of Indazole-Derived ULK1 Inhibitors.
In Silico HTS and Structure Based Optimization of Indazole-Derived ULK1 Inhibitors.
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DOI：
10.1021/acsmedchemlett.7b00344
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发表时间：
2017-11
影响因子：
4.2
通讯作者：
Spencer D Wood;Wayne Grant;I. Adrados;J. Choi;James M Alburger;Derek R Duckett;W. Roush
中科院分区：
文献类型：
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作者：
Spencer D Wood;Wayne Grant;I. Adrados;J. Choi;James M Alburger;Derek R Duckett;W. Roush
We present the outcome of an in silico high throughput screen (HTS) and optimization of a small molecule Unc-51-Like Kinase 1 (ULK1) inhibitor hit, SR-17398, with an indazole core. Docking studies guided design efforts that led to inhibitors with increased activity vs ULK1 (IC50 < 50 nM). The most advanced molecules in this inhibitor series (3a and 3g) hold promise for further development into selective ULK1 molecular probes to interrogate the biology of ULK1 and to assess whether selectively targeting autophagy is an effective anticancer strategy.
