Discovery of 2,4-dimethoxypyridines as novel autophagy inhibitors
Accepted version
Peer-reviewed
Repository URI
Repository DOI
Change log
Authors
Abstract
© 2018 Elsevier Ltd Autophagy is a catabolic process, which mediates degradation of cellular components and has important roles in health and disease. Therefore, small molecule modulators of autophagy are in great demand. Herein, we describe a phenotypic high-content screen for autophagy inhibitors, which led to the discovery of a dimethoxypyridine-based class of autophagy inhibitors, which derive from previously reported, natural product-inspired MAP4K4 inhibitors. Comprehensive structure-activity relationship studies led to a potent compound, and biological validation experiments indicated that the mode of action was upstream or independent of mTOR.
Description
Keywords
Autophagy, Phenotypic screening, High-throughput screening, Natural products, Medicinal chemistry
Journal Title
Tetrahedron
Conference Name
Journal ISSN
0040-4020
1464-5416
1464-5416
Volume Title
74
Publisher
Elsevier BV
Publisher DOI
Sponsorship
Royal Society (URF\R\180019)
European Commission (EC) (852985)
European Commission (EC) (852985)