AGN 193109, a retinoid analog, is a potent and specific antagonist of RARs (Kds: 2 nM, 2 nM, and 3 nM for RARα, RARβ, and RARγ).

RARγ:3 nM (Kd), RARβ:2 nM (Kd), RARα:2 nM (Kd)

AGN 193109 由于不与任何RXRs结合或通过其转激活，因此完全是RAR特异性的[1]。AGN 193109（100 nM）能够抑制TTNPB（一种视黄酸受体激动剂）依赖的ECE16-1细胞形态变化。在10 nM时，AGN193109能半反转视黄素依赖的生长抑制，在100 nM时则完全显示出这一效果（在ECE16-1细胞中）。AGN193109（100 nM）还能消除TTNPB引起的K5、K6、K14、K16和K17水平降低和K7、K8、K19水平升高的情况[2]。

AGN 193109 (0.30或1.20 μmol/kg) 通过局部治疗显著减少了口服TTNPB联合治疗引起的体重减轻和皮肤毒性。AGN 193109 (1.15 μmol/kg) 不会引起明显的毒性反应，对小鼠脾脏重量无影响，但它抑制了TTNPB引起的小鼠脾脏重量增加。AGN 193109 同时也显著降低了ATRA [3] 引起的皮肤毒性。

Cells (10,000/cm2) are seeded in complete medium and allowed to attach overnight. The cells are then shifted to defined medium (DM), allowed to equilibrate for 24 h, and treatment is initiated by the addition of fresh DM or DM containing epidermal growth factor (EGF) or retinoid. After 3 days of daily treatment with retinoid, the cells are harvested with 0.025% trypsin, 1 mM EDTA, fixed in isotonic buffer containing 4% formaldehyde, and counted using a counter [2].

Mice (n=6) are treated topically on the dorsal skin with vehicle (92.5% acetone/7.5% DMSO), 0.072 μmol/kg of TTNPB, 1.15 μmol/kg of AGN 193109, or 0.072 μmol/kg of TTNPB plus 0.072, 0.288, or 1.15 μmol/kg of AGN 193109 for 5 days. Mice are euthanized on Day 8 [3].