In Silico HTS and Structure Based Optimization of Indazole-Derived ULK1 Inhibitors
2017; American Chemical Society; Volume: 8; Issue: 12 Linguagem: Inglês
10.1021/acsmedchemlett.7b00344
ISSN1948-5875
AutoresSpencer D. Wood, Wayne Grant, Isabel Adrados, Jun Yong Choi, James M. Alburger, Derek R. Duckett, William Roush,
Tópico(s)Plant-Microbe Interactions and Immunity
ResumoWe 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.
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