PMID- 32189570
OWN - NLM
STAT- MEDLINE
DCOM- 20210628
LR  - 20210628
IS  - 1538-0254 (Electronic)
IS  - 0739-1102 (Linking)
VI  - 39
IP  - 5
DP  - 2021 Mar
TI  - In-silico identification of peroxisome proliferator-activated receptor (PPAR)alpha/gamma 
      agonists from Ligand Expo Components database.
PG  - 1853-1864
LID - 10.1080/07391102.2020.1745279 [doi]
AB  - PPARalpha and PPARgamma play important roles in regulating glucose and lipid metabolism. 
      In recent years, the development of dual PPAR agonists has become a hot topic in 
      the field of anti-diabetic medicinal chemistry. The dual PPARalpha/gamma agonists can 
      both improve metabolism and reduce side effects caused by single drugs, and has 
      become a promising strategy for designing effective drugs for the treatment of 
      type 2 diabetes. In this study, by means of virtual screening, molecular docking 
      and ADMET prediction technology, a representative compound with higher docking 
      score, lower toxicity than original ligands was gained from the Ligand Expo 
      Components database. It was observed through MD simulation that the 
      representative compound not only has the function of activating the PPARalpha target 
      and the PPARgamma target, but also show a more favorable binding mode when the 
      representative compound binds to the two receptors compared to the original 
      ligands. Our results provided an approach to rapidly find novel PPARalpha/gamma dual 
      agonists for the treatment of type 2 diabetes mellitus (T2DM).This paper explores 
      novel compounds targeting PPARalpha/gamma dual agonists by using molecular docking, ADMET 
      prediction, and molecular dynamics simulation methods. The specific flowchart is 
      as follows: HighlightsThe results show that the skeleton of compound M80 is not 
      only similar to Saroglitazar but also higher than that of Saroglitazar in 
      activity.This study explained the binding modes of saroglitazar-PPARalpha/gamma complexes 
      and provided structure reference for the research and development of novel 
      PPARalpha/gamma dual agonists.
FAU - Feng, Xiao-Yan
AU  - Feng XY
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Ding, Ting-Ting
AU  - Ding TT
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Liu, Ya-Ya
AU  - Liu YY
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
FAU - Xu, Wei-Ren
AU  - Xu WR
AD  - Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute 
      of Pharmaceutical Research, Tianjin, China.
FAU - Cheng, Xian-Chao
AU  - Cheng XC
AD  - Tianjin Key Laboratory on Technologies Enabling Development of Clinical 
      Therapeutics and Diagnostics (Theranostics), School of Pharmacy, Tianjin Medical 
      University, Tianjin, China.
LA  - eng
PT  - Journal Article
DEP - 20200401
PL  - England
TA  - J Biomol Struct Dyn
JT  - Journal of biomolecular structure & dynamics
JID - 8404176
RN  - 0 (Ligands)
RN  - 0 (PPAR alpha)
RN  - 0 (PPAR gamma)
SB  - IM
MH  - *Diabetes Mellitus, Type 2/drug therapy
MH  - Humans
MH  - Ligands
MH  - Molecular Docking Simulation
MH  - PPAR alpha
MH  - PPAR gamma
OTO - NOTNLM
OT  - ADMET
OT  - PPARalpha/gamma agonists
OT  - molecular dynamics
OT  - virtual screening
EDAT- 2020/03/20 06:00
MHDA- 2021/06/29 06:00
CRDT- 2020/03/20 06:00
PHST- 2020/03/20 06:00 [pubmed]
PHST- 2021/06/29 06:00 [medline]
PHST- 2020/03/20 06:00 [entrez]
AID - 10.1080/07391102.2020.1745279 [doi]
PST - ppublish
SO  - J Biomol Struct Dyn. 2021 Mar;39(5):1853-1864. doi: 
      10.1080/07391102.2020.1745279. Epub 2020 Apr 1.