Phenotypic Identification of a Novel Autophagy Inhibitor Chemotype Targeting Lipid Kinase VPS34

• DOI: 10.1002/anie.201703738
• Publication Date: 2017-05-24T00:12:15Z
• Authors: Lucas Robke; Luca Laraia; Marjorie A. Carne...; Georgios Konstant...; Makoto Muroi; André Richters; Michael Winzker; Tobias Engbring; Stefano Tomassi; Nobumoto Watanabe; Hiroyuki Osada; Daniel Rauh; Herbert Waldmann; Yao‐Wen Wu; Julian Engel
• Keywords: Chemotype; Identification

Autophagy is a critical regulator of cellular homeostasis and metabolism. Interference with this process considered new approach for the treatment disease, in particular cancer neurological disorders. Therefore, novel small-molecule autophagy modulators are high demand. We describe discovery autophinib, potent inhibitor chemotype. Autophinib was identified by means phenotypic assay monitoring formation autophagy-induced puncta, indicating accumulation lipidated cytosolic protein LC3 on autophagosomal membrane. Target identification validation revealed that autophinib inhibits induced starvation or rapamycin targeting lipid kinase VPS34.