PMID- 36014530
OWN - NLM
STAT- MEDLINE
DCOM- 20220829
LR  - 20220830
IS  - 1420-3049 (Electronic)
IS  - 1420-3049 (Linking)
VI  - 27
IP  - 16
DP  - 2022 Aug 19
TI  - Overview of Research into mTOR Inhibitors.
LID - 10.3390/molecules27165295 [doi]
LID - 5295
AB  - The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that 
      belongs to the phosphoinositide 3-kinase (PI3K)-related kinase (PIKK) family. The 
      kinase exists in the forms of two complexes, mTORC1 and mTORC2, and it 
      participates in cell growth, proliferation, metabolism, and survival. The kinase 
      activity is closely related to the occurrence and development of multiple human 
      diseases. Inhibitors of mTOR block critical pathways to produce antiviral, 
      anti-inflammatory, antiproliferative and other effects, and they have been 
      applied to research in cancer, inflammation, central nervous system diseases and 
      viral infections. Existing mTOR inhibitors are commonly divided into mTOR 
      allosteric inhibitors, ATP-competitive inhibitors and dual binding site 
      inhibitors, according to their sites of action. In addition, there exist several 
      dual-target mTOR inhibitors that target PI3K, histone deacetylases (HDAC) or 
      ataxia telangiectasia mutated and Rad-3 related (ATR) kinases. This review 
      focuses on the structure of mTOR protein and related signaling pathways as well 
      as the structure and characteristics of various mTOR inhibitors. Non-rapalog 
      allosteric inhibitors will open new directions for the development of new 
      therapeutics specifically targeting mTORC1. The applications of ATP-competitive 
      inhibitors in central nervous system diseases, viral infections and inflammation 
      have laid the foundation for expanding the indications of mTOR inhibitors. Both 
      dual-binding site inhibitors and dual-target inhibitors are beneficial in 
      overcoming mTOR inhibitor resistance.
FAU - Mao, Beibei
AU  - Mao B
AD  - College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 
      250355, China.
FAU - Zhang, Qi
AU  - Zhang Q
AD  - College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 
      250355, China.
FAU - Ma, Li
AU  - Ma L
AUID- ORCID: 0000-0003-3458-7754
AD  - Shandong Provincial Key Laboratory of Molecular Engineering, State Key Laboratory 
      of Biobased Material and Green Papermaking, School of Chemistry and Chemical 
      Engineering, Qilu University of Technology (Shandong Academy of Sciences), Jinan 
      250353, China.
FAU - Zhao, Dong-Sheng
AU  - Zhao DS
AUID- ORCID: 0000-0003-3265-5442
AD  - College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 
      250355, China.
FAU - Zhao, Pan
AU  - Zhao P
AD  - College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 
      250355, China.
FAU - Yan, Peizheng
AU  - Yan P
AUID- ORCID: 0000-0002-1955-4412
AD  - College of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan 
      250355, China.
LA  - eng
GR  - ZR2019BB031/Shandong Provincial Natural Science Foundation/
GR  - 82004233/National Natural Science Foundation of China/
GR  - 81903780/National Natural Science Foundation of China/
GR  - ZR2020QB114/Shandong Provincial Natural Science Foundation/
PT  - Journal Article
PT  - Review
DEP - 20220819
PL  - Switzerland
TA  - Molecules
JT  - Molecules (Basel, Switzerland)
JID - 100964009
RN  - 0 (MTOR Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenosine Triphosphate/metabolism
MH  - Humans
MH  - Inflammation
MH  - *MTOR Inhibitors
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - *Phosphatidylinositol 3-Kinases/metabolism
MH  - Protein Kinase Inhibitors/pharmacology/therapeutic use
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC9413691
OTO - NOTNLM
OT  - dual inhibitors
OT  - human diseases
OT  - mTOR
OT  - mTOR inhibitors
COIS- The authors declare no conflict of interest.
EDAT- 2022/08/27 06:00
MHDA- 2022/08/30 06:00
PMCR- 2022/08/19
CRDT- 2022/08/26 01:37
PHST- 2022/07/29 00:00 [received]
PHST- 2022/08/15 00:00 [revised]
PHST- 2022/08/18 00:00 [accepted]
PHST- 2022/08/26 01:37 [entrez]
PHST- 2022/08/27 06:00 [pubmed]
PHST- 2022/08/30 06:00 [medline]
PHST- 2022/08/19 00:00 [pmc-release]
AID - molecules27165295 [pii]
AID - molecules-27-05295 [pii]
AID - 10.3390/molecules27165295 [doi]
PST - epublish
SO  - Molecules. 2022 Aug 19;27(16):5295. doi: 10.3390/molecules27165295.