Dated: Feb 07, 2022
Publication Name: Pharmaceuticals
Citations : The p97 Inhibitor UPCDC-30245 Blocks Endo-Lysosomal Degradation
The diverse modes of action of small molecule inhibitors provide versatile tools to investigate basic biology and develop therapeutics. However, it remains a challenging task to evaluate their exact mechanisms of action. We identified two classes of inhibitors for the p97 ATPase: ATP competitive and allosteric. We showed that the allosteric p97 inhibitor, UPCDC-30245, does not affect two well-known cellular functions of p97, endoplasmic-reticulum-associated protein degradation and the unfolded protein response pathway; instead, it strongly increases the lipidated form of microtubule-associated proteins 1A/1B light chain 3B (LC3-II), suggesting an alteration of autophagic pathways.
Contributors: Feng Wang, Shan Li, Kai-Wen Cheng, William M. Rosencrans and Tsui-Fen Chou