PMID- 36503229
OWN - NLM
STAT- MEDLINE
DCOM- 20221223
LR  - 20230105
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 65
IP  - 24
DP  - 2022 Dec 22
TI  - Targeting the PI3K/AKT/mTOR Signaling Pathway in the Treatment of Human Diseases: 
      Current Status, Trends, and Solutions.
PG  - 16033-16061
LID - 10.1021/acs.jmedchem.2c01070 [doi]
AB  - 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.
FAU - Huang, Jindi
AU  - Huang J
AD  - 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.
FAU - Chen, Liye
AU  - Chen L
AD  - 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.
FAU - Wu, Jiangxia
AU  - Wu J
AD  - 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.
FAU - Ai, Daiqiao
AU  - Ai D
AD  - 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.
FAU - Zhang, Ji-Quan
AU  - Zhang JQ
AUID- ORCID: 0000-0002-8034-7551
AD  - College of Pharmacy, Guizhou Medical University, Guiyang 550004, China.
FAU - Chen, Tie-Gen
AU  - Chen TG
AD  - 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.
FAU - Wang, Ling
AU  - Wang L
AUID- ORCID: 0000-0001-5116-7749
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20221212
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.1.1 (MTOR protein, human)
SB  - IM
MH  - Humans
MH  - *Proto-Oncogene Proteins c-akt/metabolism
MH  - *Phosphatidylinositol 3-Kinase/metabolism
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Prospective Studies
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases
EDAT- 2022/12/13 06:00
MHDA- 2022/12/24 06:00
CRDT- 2022/12/12 09:03
PHST- 2022/12/13 06:00 [pubmed]
PHST- 2022/12/24 06:00 [medline]
PHST- 2022/12/12 09:03 [entrez]
AID - 10.1021/acs.jmedchem.2c01070 [doi]
PST - ppublish
SO  - J Med Chem. 2022 Dec 22;65(24):16033-16061. doi: 10.1021/acs.jmedchem.2c01070. 
      Epub 2022 Dec 12.