264W94 is a robust inhibitor of the ileal bile acid transporter (IBAT) and a novel agent for reducing cholesterol levels. It exhibits CYP7A1 induction and demonstrates significant antilipemic activity.

The compound 264W94, at concentrations of 0, 0.1, 0.25, and 0.5 μM, decreases the human IBAT-specific transport of 5 μM TC by 14% to 75%, demonstrating a concentration-dependent inhibition, with an IC50 of 0.25 μM observed in CHO-hIBAT cells [1].

264W94 (orally; 0.03-1.0 mg/kg; twice a day for 3.5 days) dose-dependently attenuates diet-induced increases in serum LDL+VLDL-C and prevents the decrease in HDL-C. Additionally, 264W94 (orally; 0.003, 0.01, 0.03, 0.1 mg/kg; twice a day for 2 days) enhances fecal excretion of 75SeHCAT in a dose-dependent manner [1]. Furthermore, 264W94 (0.001, 0.01, 0.1, 1, and 10 mg/kg; twice a day for 2 weeks) dose-dependently reduces plasma glucose in male ZDF (ZDF/GmiCrl-fa/fa) rats and prevents insulin decline without increasing proinsulin levels [2].

Animal Model: Male Sprague Dawley rats (CD, Charles River, 270-310 gm). Dosage: 0.03, 0.1, 0.3, 1.0 mg/kg. Administration: Orally; twice a day (9:00 am and 3:30 pm) for 3.5 days [1]