Wang Tianyi, Long Kaiqi, Zhou Yang, Jiang Xiaoding, Liu Jinzhao, Fong John H C, Wong Alan S L, Ng Wai-Lung, Wang Weiping
State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
ACS Pharmacol Transl Sci. 2022 Feb 8;5(3):149-155. doi: 10.1021/acsptsci.1c00230. eCollection 2022 Mar 11.
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.
作为细胞代谢、增殖和存活的重要调节因子，雷帕霉素哺乳动物靶蛋白（mTOR）信号传导既是癌症治疗的潜在靶点，也是研究细胞代谢的研究工具。一种同时作用于mTORC1和mTORC2途径的抑制剂OSI-027，显示出强大的抗癌功效，但会引发副作用。在此，我们设计了一种光可激活的OSI-027前药，其在光照后可释放OSI-027以抑制mTOR信号通路，触发自噬并导致细胞死亡。这种光可激活前药可为mTOR靶向癌症治疗提供新策略，并作为研究mTOR信号传导及其相关生物学过程的新工具。
