AGN194310

Biochem/physiol Actions

AGN194310 (IRX4310; VTP 194310) is a retinoic acid receptor (RAR) antagonist that targets all three RAR subtypes with higher affinity (RARα/β/γ K_d = 3/2/5 nM) than all-trans retinoic acid/ATRA (RARα/β/γ K_d = 15/13/18 nM) without affecting RXR subtypes. AGN194310 effectively blocks RAR agonist TTNPB-induced transcription activity (using RARα, RARβ, or RARγ transfected cells) and prevents TTNPB toxicity in guinea pigs in vivo (by 79/84/94% at AGN194310/TTNPB ratios of 0.5/2/8). AGN194310 potentiates differentiation in osteoblast cultures (1 µM) and daily oral administration (0.5 mg/kg/d for a10-d period) is reported to cause impaired radial bone growth among 8-wk-old mice.