Disease relevance of Agn 191701

• (E)-2-[2-(5,6,7,8-Tetrahydro-3,5,5,8,8-pentamethyl-2-naphthyl) propen-1-yl]-4-thiophenecarboxylic acid (AGN 191701) and other retinoid X receptor (RXR)-selective agonists were observed to cause hepatomegaly in rats [1].
• To determine if AGN 191701-induced hepatic hyperplasia was sustained, rats were treated by gavage with 60 mumol/kg of AGN 191701 for up to 7 days and exposed to BrdU via osmotic pump on days 1-3 or on days 6-8 [1].
• Two RXR-selective agonists, LG100268 and AGN 191701, failed to induce hypertriglyceridemia or weight loss up to the highest doses tested [2].

High impact information on Agn 191701

• Hepatocyte L1 and mitotic index were increased only in rats exposed to BrdU on days 1-3, indicating that AGN 191701-induced hepatocyte proliferation was transient [1].
• AGN 191701 caused dose-dependent hepatomegaly in the absence of hepatic necrosis and necrosis and increased hepatocyte BrdU labeling index (LI) [1].
• To determine if RXR agonists have biochemical effects in common with a peroxisome proliferator, various endpoints were measured 24 hr after two daily treatments with AGN 191701, SR11237, or clofibrate [1].
• The ED50 value of the RXR-selective AGN 191701 was 600 nmol/animal compared with an ED50 value of 0.2 nmol for the structurally similar RAR-selective TTNPB [3].

References