PMID- 32966896
OWN - NLM
STAT- MEDLINE
DCOM- 20210526
LR  - 20211204
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 208
DP  - 2020 Dec 15
TI  - Research progress of mTOR inhibitors.
PG  - 112820
LID - S0223-5234(20)30792-3 [pii]
LID - 10.1016/j.ejmech.2020.112820 [doi]
AB  - Mammalian target of rapamycin (mTOR) is a highly conserved Serine/Threonine 
      (Ser/Thr) protein kinase, which belongs to phosphatidylinositol-3-kinase-related 
      kinase (PIKK) protein family. mTOR exists as two types of protein complex: mTORC1 
      and mTORC2, which act as central controller regulating processes of cell 
      metabolism, growth, proliferation, survival and autophagy. The mTOR inhibitors 
      block mTOR signaling pathway, producing anti-inflammatory, anti-proliferative, 
      autophagy and apoptosis induction effects, thus mTOR inhibitors are mainly used 
      in cancer therapy. At present, mTOR inhibitors are divided into four categories: 
      Antibiotic allosteric mTOR inhibitors (first generation), ATP-competitive mTOR 
      inhibitors (second generation), mTOR/PI3K dual inhibitors (second generation) and 
      other new mTOR inhibitors (third generation). In this article, these four 
      categories of mTOR inhibitors and their structures, properties and some clinical 
      researches will be introduced. Among them, we focus on the structure of mTOR 
      inhibitors and try to analyze the structure-activity relationship. mTOR 
      inhibitors are classified according to their chemical structure and their 
      contents are introduced systematically. Moreover, some natural products that have 
      direct or indirect mTOR inhibitory activities are introduced together. In this 
      article, we analyzed the target, binding mode and structure-activity relationship 
      of each generation of mTOR inhibitors and proposed two hypothetic scaffolds (the 
      inverted-Y-shape scaffold and the C-shape scaffold) for the second generation of 
      mTOR inhibitors. These findings may provide some help or reference for drug 
      designing, drug modification or the future development of mTOR inhibitor.
CI  - Copyright (c) 2020 Elsevier Masson SAS. All rights reserved.
FAU - Chen, Yifan
AU  - Chen Y
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China.
FAU - Zhou, Xiaoping
AU  - Zhou X
AD  - School of Pharmaceutical Sciences, Jilin University, Changchun, 130021, China. 
      Electronic address: zhouxp@jlu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20200913
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Molecular Structure
MH  - Protein Kinase Inhibitors/chemistry/metabolism/*therapeutic use
MH  - Signal Transduction/drug effects
MH  - Structure-Activity Relationship
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Anticancer
OT  - Drug design
OT  - mTOR
OT  - mTOR inhibitor
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2020/09/24 06:00
MHDA- 2021/05/27 06:00
CRDT- 2020/09/23 20:05
PHST- 2020/07/17 00:00 [received]
PHST- 2020/08/16 00:00 [revised]
PHST- 2020/09/03 00:00 [accepted]
PHST- 2020/09/24 06:00 [pubmed]
PHST- 2021/05/27 06:00 [medline]
PHST- 2020/09/23 20:05 [entrez]
AID - S0223-5234(20)30792-3 [pii]
AID - 10.1016/j.ejmech.2020.112820 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2020 Dec 15;208:112820. doi: 10.1016/j.ejmech.2020.112820. Epub 
      2020 Sep 13.