PMID- 8308867
OWN - NLM
STAT- MEDLINE
DCOM- 19940315
LR  - 20190709
IS  - 0022-2623 (Print)
IS  - 0022-2623 (Linking)
VI  - 37
IP  - 3
DP  - 1994 Feb 4
TI  - Synthesis of high specific activity [3H]-9-cis-retinoic acid and its application 
      for identifying retinoids with unusual binding properties.
PG  - 408-14
AB  - all-trans-Retinoic acid is known to bind to the retinoic acid receptors (RARs) 
      resulting in an increase in their transcriptional activity. In contrast, recently 
      identified 9-cis-retinoic acid (9-cis-RA), which is an additional endogenous RA 
      isomer, is capable of binding to both RARs and retinoid X receptors (RXRs). These 
      distinct properties have raised questions as to the biological role governed by 
      these two retinoic acid isomers and the set of target genes that they regulate. 
      Herein, we report the synthesis of high specific activity [3H]-9-cis-RA and its 
      application to study the ligand-binding properties of the various retinoid 
      receptor subtypes. We examined the binding properties of RARs and RXRs for a 
      series of synthetic retinoids and compared the ligand-binding properties of these 
      arotinoid analogs with their ability to regulate gene expression via the retinoid 
      receptors in a cotransfection assay. The utilization of the [3H]-9-cis-RA 
      competitive binding assay and the cotransfection assay has made it possible to 
      rapidly identify important structural features of retinoids leading to increased 
      selectivity for either the RAR or RXR receptor subtypes.
FAU - Boehm, M F
AU  - Boehm MF
AD  - Department of Medicinal Chemistry, Ligand Pharmaceuticals, Incorporated, San 
      Diego, California 92121.
FAU - McClurg, M R
AU  - McClurg MR
FAU - Pathirana, C
AU  - Pathirana C
FAU - Mangelsdorf, D
AU  - Mangelsdorf D
FAU - White, S K
AU  - White SK
FAU - Hebert, J
AU  - Hebert J
FAU - Winn, D
AU  - Winn D
FAU - Goldman, M E
AU  - Goldman ME
FAU - Heyman, R A
AU  - Heyman RA
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Benzoates)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Retinoids)
RN  - 0 (Transcription Factors)
RN  - 10028-17-8 (Tritium)
RN  - 5688UTC01R (Tretinoin)
RN  - 71441-28-6 
      (4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic 
      acid)
SB  - IM
MH  - Animals
MH  - Baculoviridae/genetics
MH  - Benzoates/metabolism
MH  - Binding, Competitive
MH  - Methylation
MH  - Molecular Structure
MH  - Moths
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Receptors, Retinoic Acid/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Retinoid X Receptors
MH  - Retinoids/metabolism
MH  - Structure-Activity Relationship
MH  - *Transcription Factors
MH  - Transfection
MH  - Tretinoin/*chemical synthesis/chemistry/metabolism
MH  - Tritium
EDAT- 1994/02/04 00:00
MHDA- 1994/02/04 00:01
CRDT- 1994/02/04 00:00
PHST- 1994/02/04 00:00 [pubmed]
PHST- 1994/02/04 00:01 [medline]
PHST- 1994/02/04 00:00 [entrez]
AID - 10.1021/jm00029a013 [doi]
PST - ppublish
SO  - J Med Chem. 1994 Feb 4;37(3):408-14. doi: 10.1021/jm00029a013.