2.Aurone derivatives as Vps34 inhibitors that modulate autophagy.
Guodong LI ; Joshua William BOYLE ; Chung-Nga KO ; Wu ZENG ; Vincent Kam Wai WONG ; Jian-Bo WAN ; Philip Wai Hong CHAN ; Dik-Lung MA ; Chung-Hang LEUNG
Acta Pharmaceutica Sinica B 2019;9(3):537-544
We report in this study the identification of a natural product-like antagonist () of Vps34 as a potent autophagy modulator structure-based virtual screening. Aurone derivative strongly inhibited Vps34 activity in cell-free and cell-based assays. Significantly, prevents autophagy in human cells induced either by starvation or by an mTOR inhibitor. modeling and kinetic data revealed that could function as an ATP-competitive inhibitor of Vps34. Moreover, it suppressed autophagy and without inducing heart or liver damage in mice. could be utilized as a new motif for more selective and efficacious antagonists of Vps34 for the potential treatment of autophagy-related human diseases.
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