Optochemical Control of mTOR Signaling and mTOR-Dependent Autophagy.
Tianyi WangKaiqi LongYang ZhouXiaoding JiangJinzhao LiuJohn H C FongAlan S L WongWai-Lung NgWeiping WangPublished in: ACS pharmacology & translational science (2022)
As an important regulator of cell metabolism, proliferation, and survival, mTOR (mammalian target of rapamycin) signaling provides both a potential target for cancer treatment and a research tool for investigation of cell metabolism. One inhibitor for both mTORC1 and mTORC2 pathways, OSI-027, exhibited robust anticancer efficacy but induced side effects. Herein, we designed a photoactivatable OSI-027 prodrug, which allowed the release of OSI-027 after light irradiation to inhibit the mTOR signaling pathway, triggering autophagy and leading to cell death. This photoactivatable prodrug can provide novel strategies for mTOR-targeting cancer therapy and act as a new tool for investigating mTOR signaling and its related biological processes.