Discovery of a Novel Photocaged PI3K Inhibitor Capable of Real-Time Reporting of Drug Release

  • ACS Med Chem Lett. 2023 Jul 24;14(8):1100-1107. doi: 10.1021/acsmedchemlett.3c00240.
Hua Tian  1  2  3 ,  Shen You  1  3 ,  Tianning Xiong  1  2  3 ,  Ming Ji  1  3 ,  Kehui Zhang  1  2  3 ,  Lin Jiang  1  2  3 ,  Tingting Du  1  3 ,  Ying Li  1  2  3 ,  Wenqian Liu  1  2  3 ,  Songwen Lin  1  2  3 ,  Xiaoguang Chen  1  3 ,  Heng Xu  1  2  3
Affiliations
  • 1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 2. Beijing Key Laboratory of Active Substances Discovery and Drugability Evaluation, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
  • 3. Key Laboratory of Small Molecule Immuno-Oncology Drug Discovery, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
PMID: 37583818 DOI: 10.1021/acsmedchemlett.3c00240
Abstract

A novel photocaged PI3K Inhibitor 2 was designed and synthesized by introducing a cascade photocaging group to block its key interaction with the kinase. Upon UV light irradiation, the photocaged compound released a highly potent PI3K Inhibitor to recover its Anticancer properties and a Fluorescent Dye for real-time reporting of drug release, providing a new approach for studying the PI3K signaling transduction pathway as well as developing precisely controlled Cancer therapeutics.

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