Targeting the PI3K/AKT/mTOR Signaling Pathway in the Treatment of Human Diseases: Current Status, Trends, and Solutions.
Jindi HuangLiye ChenJiangxia WuDaiqiao AiJi-Quan ZhangTie-Gen ChenLing WangPublished in: Journal of medicinal chemistry (2022)
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.
Keyphrases
- cell proliferation
- signaling pathway
- current status
- endothelial cells
- cancer therapy
- protein kinase
- pulmonary fibrosis
- pi k akt
- type diabetes
- cardiovascular disease
- induced pluripotent stem cells
- cell cycle
- pluripotent stem cells
- adipose tissue
- metabolic syndrome
- skeletal muscle
- tyrosine kinase
- combination therapy
- free survival