Background:

S-8921 is an ileal Na+/bile acid cotransporter (IBAT) inhibitor.

S-8921 is an ileal Na+/bile acid cotransporter (IBAT) inhibitor. S-8921 inhibits the uptake velocity of 60 μM [3H] taurocholate dose-dependently in IBAT-COS cells, and the IC50 value of S-8921 is 66±8 μM[1].

Seven-day treatment with S-8921 causes a dramatic decrease of serum cholesterol concentrations in hamsters. The hypocholesterolemic effects of S-8921 are dose-dependent, but S-8921 does not affect body weight. An increase of fecal bile acid excretion is observed especially at higher doses of S-8921[1]. S-8921 treatment for 1 to 2 weeks causes a decrease in serum total cholesterol concentrations, with 0.01% S-8921 (4.0 to 4.6 mg/kg) being almost maximally effective[2].

[1]. Hara S, et al. S-8921, an ileal Na+/bile acid cotransporter inhibitor decreases serum cholesterol in hamsters. Life Sci. 1997;60(24):PL 365-70. [2]. Higaki J, et al. Inhibition of ileal Na+/bile acid cotransporter by S-8921 reduces serum cholesterol and prevents atherosclerosis in rabbits. Arterioscler Thromb Vasc Biol. 1998 Aug;18(8):1304-11.