Discovery of 2,4-dimethoxypyridines as novel autophagy inhibitors

Lucas Robke, Tiago Rodrigues, Peter Schröder, Daniel J. Foley, Gonçalo J.L. Bernardes, Luca Laraia*, Herbert Waldmann

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

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
Original languageEnglish
JournalTetrahedron
Volume74
Pages (from-to)4531-4537
ISSN0040-4020
DOIs
Publication statusPublished - 2018

Keywords

  • Autophagy
  • Phenotypic screening
  • High-throughput screening
  • Natural products
  • Medicinal chemistry

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