Optochemical Control of mTOR Signaling and mTOR-Dependent Autophagy

Tianyi Wang; Kaiqi Long; Yang Zhou; Xiaoding Jiang; Jinzhao Liu; John H C Fong; Alan S L Wong; Wai-Lung Ng; Weiping Wang

doi:10.1021/acsptsci.1c00230

Optochemical Control of mTOR Signaling and mTOR-Dependent Autophagy

ACS Pharmacol Transl Sci. 2022 Feb 8;5(3):149-155. doi: 10.1021/acsptsci.1c00230. eCollection 2022 Mar 11.

Authors

Tianyi Wang^{1

2

3}, Kaiqi Long^{1

2

3}, Yang Zhou^{1

2

3}, Xiaoding Jiang⁴, Jinzhao Liu³, John H C Fong⁵, Alan S L Wong^{5

6}, Wai-Lung Ng⁴, Weiping Wang^{1

2

3}

Affiliations

¹ State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.
² Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
³ Dr. Li Dak-Sum Research Centre, The University of Hong Kong, Hong Kong 0000, China.
⁴ School of Pharmacy, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
⁵ Laboratory of Combinatorial Genetics and Synthetic Biology, School of Biomedical Sciences, The University of Hong Kong, Hong Kong China.
⁶ Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, China.

Abstract

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.