Identification of synthetic retinoids with selectivity for human nuclear retinoic acid receptor gamma.
The action of retinoids on gene regulation is mediated by three distinct nuclear retinoic acid receptor (RAR) subtypes called RAR alpha, beta and gamma. Since RAR gamma is predominantly expressed in adult skin, specific ligands for this subtype could (i) represent valuable tools to evaluate the biological role of RAR gamma in skin and (ii) provide therapeutic entities with a higher therapeutic index at lower teratogenic risk. Using in vitro binding studies and a functional transactivation assay, we have identified three compounds with high RAR gamma selectivity.
Bernard
B A
BA
Centre International de Recherches Dermatologiques Galderma (CIRD Galderma), Valbonne, France.
Bernardon
J M
JM
Delescluse
C
C
Martin
B
B
Lenoir
M C
MC
Maignan
J
J
Charpentier
B
B
Pilgrim
W R
WR
Reichert
U
U
Shroot
B
B
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015195:Drug Design; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D018168:Receptors, Retinoic Acid; D012176:Retinoids / Q000138:chemical synthesis / Q000378:metabolism* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D012176:Retinoids; D015500:Chloramphenicol O-Acetyltransferase