2. Academic Validation
  3. Targeting the PI3K/AKT/mTOR Signaling Pathway in the Treatment of Human Diseases: Current Status, Trends, and Solutions

Targeting the PI3K/AKT/mTOR Signaling Pathway in the Treatment of Human Diseases: Current Status, Trends, and Solutions

  • J Med Chem. 2022 Dec 22;65(24):16033-16061. doi: 10.1021/acs.jmedchem.2c01070.
Jindi Huang 1,  Liye Chen 1,  Jiangxia Wu 1,  Daiqiao Ai 1,  Ji-Quan Zhang 2,  Tie-Gen Chen 3,  Ling Wang 1
Affiliations

Affiliations

  • 1 Guangdong Provincial Key Laboratory of Fermentation and Enzyme Engineering, Joint International Research Laboratory of Synthetic Biology and Medicine, Guangdong Provincial Engineering and Technology Research Center of Biopharmaceuticals, School of Biology and Biological Engineering, South China University of Technology, Guangzhou 510006, China.
  • 2 College of Pharmacy, Guizhou Medical University, Guiyang 550004, China.
  • 3 Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Room 109, Building C, SSIP Healthcare and Medicine Demonstration Zone, Zhongshan Tsuihang New District, Zhongshan, Guangdong 528400, China.
PMID: 36503229 DOI: 10.1021/acs.jmedchem.2c01070
Abstract

The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway is one of the most important intracellular pathways involved in cell proliferation, growth, differentiation, and survival. Therefore, this route is a prospective biological target for treating various human diseases, such as tumors, neurodegenerative diseases, pulmonary fibrosis, and diabetes. An increasing number of clinical studies emphasize the necessity of developing novel molecules targeting the PI3K/Akt/mTOR pathway. This review focuses on recent advances in ATP-competitive inhibitors, allosteric inhibitors, covalent inhibitors, and proteolysis-targeting chimeras against the PI3K/Akt/mTOR pathway, and highlights possible solutions for overcoming the toxicities and acquired drug resistance of currently available drugs. We also provide recommendations for the future design and development of promising drugs targeting this pathway.

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