OSU-ERβ-12 is a selective orally active ERβ agonist capable of crossing the blood-brain barrier, exhibiting an EC50 of 78.3 nM and a Ki of 2.02 nM. It demonstrates over 200-fold selectivity for ERβ over ERα. OSU-ERβ-12 binds strongly to ERβ and reduces the expression of TGF-β-mediated profibrotic genes, thereby aiding in the reduction of liver fibrosis. This compound is useful for studying fibrotic liver diseases, non-alcoholic fatty liver disease (NAFLD), and neuroinflammation.

ERβ:78.3 nM (EC50)

OSU-ERβ-12 (1 μM; 18 hours; HEK-293 cells) exhibits high selectivity for hERβ. It remains highly stable in human liver microsomes at concentrations of 10 μM to 30 μM for 60 minutes. The compound demonstrates a high protein binding rate in plasma across multiple species, including mice, rats, monkeys, and humans, at 2 μM for 6 hours. OSU-ERβ-12 (30 μM; 5 minutes; Chinese Hamster Ovary cells expressing hERG potassium channels) does not inhibit hERG potassium channels. Additionally, at 24 hours, it reduces the expression of TGF-β-mediated pro-fibrotic genes (MCP-1, TGF-β, COL1A1) in a co-culture system of human hepatocellular carcinoma cells (HepG2) and human hepatic stellate cells (LX-2).

OSU-ERβ-12, administered at doses of 10 mg/kg and 100 mg/kg via gavage once daily for 4 weeks, can reduce liver fibrosis in a CCl4-induced mouse model of hepatic fibrosis. When given at doses of 20 mg/kg and 50 mg/kg orally for 6 consecutive days, OSU-ERβ-12 elevates plasma and brain concentrations as well as uterine mass in a non-metastatic breast tumor model in 67NR mice. At a dose of 50 mg/kg for 6 days in OVX mice, OSU-ERβ-12 increases IL-6 expression in the hypothalamus, predominantly driven by tumor-bearing mice. In sham-operated mice, the same dosage increases Gper1 and Cyp19a1 expression in the prefrontal cortex, but such effects are absent in tumor-bearing mice.