AGN 193109 (sodium salt)

AGN 193109 is a potent antagonist of retinoic acid receptors (RARs; Kd = 2, 2, and 3 nM for RARα, β, and γ, respectively). It is selective for RARs over retinoid X receptors (RXRs; Kd = >10,000 nM for human RXRα, β, and γ receptors). AGN 193109 reverses changes in cell morphology induced by the RAR agonist TTNPB in ECE16-1 human endometrial ectocervical epithelial cells. It also reverses the growth suppressive effects of all-trans-RA, 13-cis-RA, and 9-cis-RA when used at a 10-fold molar excess. AGN 193109 decreases expression of cytokeratin K5-8, 13, 14, 16, 17, and 19 genes, markers of retinoid action in ECE16-1 cells, when co-administered with TTNPB but not when used alone. In vivo, AGN 193109 induces cleft palate or frontonasal dysplasia and eye malformations in fetuses of pregnant mice following a single oral dose of 1 mg/kg.