in vitro: GSK2330672 is a highly potent, nonabsorbable ASBT inhibitor with excellent aqueous solubility, selectivity, and developability properties for evaluation in safety studies and ultimately humans. GSK2330672 will be a valuable clinical tool for exploring the therapeutic utility of a nonabsorbable ASBT inhibitor for treatment of patients with type 2 diabetes. in vivo: GSK2330672 results in potent inhibition of ASBT and very low oral absorption in the rat. GSK2330672 shows potent mouse and rat ASBT activity and was stable in GI stability assays. GSK2330672 is stable in the rodent GI tract and potently induced fecal bile acid excretion in mice, leading us to select these three compounds for mechanistic and efficacy studies in vivo in lean rats and Zucker Diabetic Fatty (ZDF) rats, respectively.
