PMID- 27320335
OWN - NLM
STAT- MEDLINE
DCOM- 20170208
LR  - 20190907
IS  - 1873-4294 (Electronic)
IS  - 1568-0266 (Linking)
VI  - 17
IP  - 6
DP  - 2017
TI  - Natural and Structure-based RXR Ligand Scaffolds and Their Functions.
PG  - 631-662
AB  - Retinoid X receptors (RXRs) are promiscuous partners of heterodimeric 
      associations with other members of the Nuclear Receptor (NR) superfamily. Through 
      these liaisons RXR ligands ("rexinoids") either transcriptionally activate on 
      their own the "permissive" subclass of heterodimers (PPAR/RXR, LXR/RXR, FXR/RXR) 
      or synergize with partner ligands in the "non-permissive" subclass of 
      heterodimers (RAR/RXR, VDR/RXR and TR/RXR). The nature and extent of the 
      interaction of the ligand-receptor complexes with co-regulators, which is cell 
      and context-dependent, results ultimately in transcriptional modulation of 
      cognate gene networks. RXR modulators hold therapeutical potential for the 
      treatment of cancer and other diseases related to nutrient acquisition and 
      disposal, among them metabolic diseases. A rexinoid (bexarotene) has indeed 
      reached the clinic for the treatment of cutaneous T-cell lymphoma. The modulation 
      of RXR function by rexinoids acting as agonists, parcial agonists, inverse 
      agonists or antagonists is encoded in the structure of the ligandreceptor 
      complexes. A very large number of rexinoids with a wide structural diversity has 
      been published. In addition to natural products and other ligands discovered by 
      HTS or mere serendipity, most rexinoids have been rationally designed based on 
      the structures of existing complexes with RXR determined by X-Ray or based on 
      Molecular Modeling. Although the structural rationale for the modulation of the 
      ligand-receptor complexes is reasonably well understood, it has not yet been 
      possible to predict the correlation between ligand structure and physiological 
      response, particularly in the case of heterodimer-selective rexinoids.
FAU - Dominguez, Marta
AU  - Dominguez M
FAU - Alvarez, Susana
AU  - Alvarez S
FAU - de Lera, Angel R
AU  - de Lera AR
AD  - Departamento de Quimica Organica, Facultade de Quimica, CINBIO and IBIV, 
      Universidade de Vigo, Campus As Lagoas-Marcosende, 36310 Vigo, Spain.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Top Med Chem
JT  - Current topics in medicinal chemistry
JID - 101119673
RN  - 0 (Ligands)
RN  - 0 (Retinoid X Receptors)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Ligands
MH  - Protein Conformation
MH  - Retinoid X Receptors/chemistry/*physiology
EDAT- 2016/06/21 06:00
MHDA- 2017/02/09 06:00
CRDT- 2016/06/21 06:00
PHST- 2015/08/31 00:00 [received]
PHST- 2016/02/18 00:00 [revised]
PHST- 2016/02/18 00:00 [accepted]
PHST- 2016/06/21 06:00 [pubmed]
PHST- 2017/02/09 06:00 [medline]
PHST- 2016/06/21 06:00 [entrez]
AID - CTMC-EPUB-76603 [pii]
AID - 10.2174/1568026616666160617072521 [doi]
PST - ppublish
SO  - Curr Top Med Chem. 2017;17(6):631-662. doi: 10.2174/1568026616666160617072521.