T-068677

T-068677 is an experimental small molecule autophagy activator. Identified through a high-throughput screening of a compound library in pancreatic beta cells, T-068677 increases autophagic flux via an mTOR-independent pathway. It activates the canonical autophagic pathway, acting on the formation of the ULK1 complex and PI3K complex independently of mTOR, and significantly degrades the autophagic substrate SQSTM1 (p62). In preclinical studies, T-068677 mitigated lipotoxicity-induced impairment of autophagic flux in beta cells and significantly improved glucose tolerance in diabetic db/db mice, suggesting its potential as a therapeutic candidate for beta cell dysfunction in type 2 diabetes.