PMID- 8600988
OWN - NLM
STAT- MEDLINE
DCOM- 19960503
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1289
IP  - 2
DP  - 1996 Mar 15
TI  - Characterization of synthetic retinoids with selectivity for retinoic acid or 
      retinoid X nuclear receptors.
PG  - 298-304
AB  - The broad spectrum of physiological activities of retinoids is mediate d by two 
      types of receptors, the retinoic acid receptors (RARs) and the retinoid X 
      receptors (RXRs). Though they have 9-cis retinoic acid as a common ligand, the 
      amino acid sequence of their ligand binding domains is only distantly related 
      (27%). This fact makes it probable that the ligand binding pockets of RARs and 
      RXRs differ significantly with respect to their three dimensional structure. 
      Therefore, one can expect that selective ligands for these receptor subclasses do 
      exit. A clear example of a naturally existing RAR-selective retinoid is all-trans 
      retinoic acid. Here we report on two synthetic retinoids which are very closely 
      related to retinoic acid in structure yet show good receptor subclass 
      selectivity. These compounds have a saturated double bond in the polyene side 
      chain between either the 7, 8 or 9, 10 carbon atoms and are highly RAR or RXR 
      selective, respectively (as shown by receptor binding, transactivation activity 
      and the ability to induce RXR homodimer formation). In addition, we present 
      compounds of the synthetic arotinoid class which are highly RAR selective. 
      Interestingly the corresponding '9-cis analogs' are not able to bind or activate 
      RXR alpha and show greatly reduced activity on the RARs.
FAU - LeMotte, P K
AU  - LeMotte PK
AD  - F. Hoffmann-LaRoche Ltd., Basel, Switzerland.
FAU - Keidel, S
AU  - Keidel S
FAU - Apfel, C M
AU  - Apfel CM
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (Ligands)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
SB  - IM
MH  - Animals
MH  - Cell Nucleus/metabolism
MH  - Ligands
MH  - Mice
MH  - Receptors, Retinoic Acid/*drug effects
MH  - Retinoid X Receptors
MH  - Retinoids/*pharmacology
MH  - Structure-Activity Relationship
MH  - Transcription Factors/*drug effects
EDAT- 1996/03/15 00:00
MHDA- 1996/03/15 00:01
CRDT- 1996/03/15 00:00
PHST- 1996/03/15 00:00 [pubmed]
PHST- 1996/03/15 00:01 [medline]
PHST- 1996/03/15 00:00 [entrez]
AID - 0304-4165(95)00179-4 [pii]
AID - 10.1016/0304-4165(95)00179-4 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 1996 Mar 15;1289(2):298-304. doi: 
      10.1016/0304-4165(95)00179-4.