PMID- 30746761
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230123
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 120
IP  - 7
DP  - 2019 Jul
TI  - Molecular docking, dynamics, and pharmacology studies on bexarotene as an agonist 
      of ligand-activated transcription factors, retinoid X receptors.
PG  - 11745-11760
LID - 10.1002/jcb.28455 [doi]
AB  - Retinoid X receptors (RXRs) belong to the nuclear receptor superfamily, and upon 
      ligand activation, these receptors control gene transcription via either 
      homodimerization with themselves or heterodimerization with the partner-nuclear 
      receptor. The protective effects of RXRs and RXR agonists have been reported in 
      several neurodegenerative diseases, including in the retina. This study was aimed 
      to prioritize compounds from natural and synthetic origin retinoids as potential 
      RXR agonists by molecular docking and molecular dynamic simulation strategies. 
      The docking studies indicated bexarotene as a lead compound that can activate 
      various RXR receptor isoforms (alpha, beta, and gamma) and has a strong binding affinity to 
      the receptor protein than retinoic acid, which is known as a natural endogenous 
      RXR agonist. Dynamic simulation studies confirmed that the hydrogen bonding and 
      hydrophobic interactions were highly stable in all the three isoforms of the 
      RXR-bexarotene complex. To further validate the significance of the RXR receptor 
      in neurons, in vitro pharmacological treatment of neuronal SH-SY5Y cells with 
      bexarotene was performed. In vitro data from SH-SY5Y cells confirmed that 
      bexarotene activated RXR-simulated neurite outgrowth significantly. We conclude 
      that bexarotene could be potentially used as an exogenous activator of RXRs and 
      emerge as a good drug target for several neurodegenerative disorders.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Chitranshi, Nitin
AU  - Chitranshi N
AUID- ORCID: 0000-0002-8038-4387
AD  - Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South 
      Wales.
FAU - Dheer, Yogita
AU  - Dheer Y
AD  - Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South 
      Wales.
FAU - Kumar, Sanjay
AU  - Kumar S
AD  - Bioinformatics Centre, Biotech Park, Jankipuram, Lucknow, Uttar Pradesh, India.
FAU - Graham, Stuart L
AU  - Graham SL
AD  - Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South 
      Wales.
AD  - Save Sight Institute, Sydney University, Sydney, New South Wales, Australia.
FAU - Gupta, Vivek
AU  - Gupta V
AD  - Faculty of Medicine and Health Sciences, Macquarie University, Sydney, New South 
      Wales.
LA  - eng
PT  - Journal Article
DEP - 20190211
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
SB  - IM
OTO - NOTNLM
OT  - bexarotene
OT  - docking
OT  - molecular dynamics
OT  - retinoic acid
OT  - retinoid X receptors
EDAT- 2019/02/13 06:00
MHDA- 2019/02/13 06:01
CRDT- 2019/02/13 06:00
PHST- 2018/12/05 00:00 [revised]
PHST- 2018/10/22 00:00 [received]
PHST- 2018/12/06 00:00 [accepted]
PHST- 2019/02/13 06:00 [pubmed]
PHST- 2019/02/13 06:01 [medline]
PHST- 2019/02/13 06:00 [entrez]
AID - 10.1002/jcb.28455 [doi]
PST - ppublish
SO  - J Cell Biochem. 2019 Jul;120(7):11745-11760. doi: 10.1002/jcb.28455. Epub 2019 
      Feb 11.