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Updated: Sep 29, 2025

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Optochemical Control of mTOR Signaling and mTOR-Dependent Autophagy

Tianyi Wang1,2,3, Kaiqi Long1,2,3, Yang Zhou1,2,3

  • 1State Key Laboratory of Pharmaceutical Biotechnology, The University of Hong Kong, Hong Kong, China.

ACS Pharmacology & Translational Science
|March 21, 2022
PubMed

Insights

Researchers developed a light-activated prodrug of OSI-027 to target the mammalian target of rapamycin (mTOR) pathway. This photoactivatable drug offers a new strategy for cancer therapy by precisely controlling mTOR inhibition, triggering cell death.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Mammalian target of rapamycin (mTOR) signaling regulates crucial cellular processes like metabolism, proliferation, and survival.
  • mTOR is a significant target for cancer therapy and a tool for studying cell metabolism.
  • The mTOR inhibitor OSI-027 shows anticancer effects but causes side effects.

Purpose of the Study:

  • To design a photoactivatable prodrug of OSI-027 for targeted mTOR inhibition.
  • To investigate the potential of this prodrug in cancer therapy and as a research tool.

Main Methods:

  • Design and synthesis of a photoactivatable OSI-027 prodrug.
  • Light irradiation to release active OSI-027.
  • Assessment of mTOR pathway inhibition, autophagy induction, and cell death.

Main Results:

  • The photoactivatable prodrug successfully released OSI-027 upon light irradiation.
  • Inhibition of the mTOR signaling pathway was achieved.
  • Light-triggered drug release induced autophagy and subsequent cancer cell death.

Conclusions:

  • Photoactivatable OSI-027 prodrugs offer a novel strategy for precise mTOR-targeting cancer therapy.
  • This approach allows for controlled inhibition of mTOR signaling, minimizing systemic side effects.
  • The prodrug serves as a valuable tool for studying mTOR signaling and related biological processes.

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