Sobetirome (IACS-010759) is a selective agonist of thyroid hormone receptor β (TRβ) and binds selectively to TRβ-1 (EC50: 0.16 μM).

TRα 1:0.58 μM (EC50), TRβ 1:0.16 μM (EC50)

GC-1 was designed to bind selectively to TRβ (EC50: 0.58 μM for TRα-1, 0.16 μM for TRβ-1) [1]. The thyromimetic agent GC-1 induces hepatocyte proliferation via Wnt/β-catenin signaling and may promote regeneration in both acute and chronic liver insufficiencies [2].

Four weeks following injection, mice were fed 5 mg/kgSobetirome or basal diet for 10 or 21 days. Treatment withSobetirome for 10 or 21 days led to a significant reduction in tumor burden [2].Sobetirome treatment reduced serum cholesterol levels by 25% and serum triglycerides by 75% in chow-fed mice and also attenuated diet-induced hypercholesterolemia [3].Sobetirome (50 or 100 mug/100 g body weight) strongly stimulates rat hepatocyte proliferation in the absence of tissue injury.Sobetirome also induced massive pancreatic cell proliferation [4].

Briefly, 20 μg of a pT3-EF5α-hMet-V5 and pT3-EF5α-S45Y-β-catenin-Myc combination along with the transposase in a ratio of 25:1 were diluted in 2 mL of normal saline (0.9% NaCl), filtered through a 0.22-μm filter, and injected into the lateral tail vein of 23 FVB mice that were around 6 weeks old, in 5 to 7 seconds. These mice are referred henceforth as hMet-mutant-β-catenin mice. Four weeks after injection, hMet-mutant-β-catenin mice were randomized into two groups. One group was kept on a basal diet (n = 12), and another group was switched to a GC-1–supplemented diet (5 mg/kg of diet) (n = 11). Animals on control diet were sacrificed at either 21 days (n = 8) or 10 days (n = 4) after initiation of the diet. Similarly, animals on the GC-1 diet were sacrificed at either 21 days (n = 7) or 10 days (n = 4) after initiation of the diet. The animals were given access to food and water ad libitum with a 12-hour light/dark daily cycle. One intraperitoneal injection of bromodeoxyuridine (BrdU) was performed on day 9 during 10 days of GC-1 or basal diet treatment, and livers were harvested 24 hours later [2].