Taladegib, a small-molecule antagonist of the smoothened receptor, shows a slight inhibitory effect on cell proliferation without differences between mucin- (IC50: Taladegib=49.8±4.5 μM) and mixed- Cholangiocarcinoma (CCA) (IC50: Taladegib=61.2±21.1 μM). The IC50 for Taladegib inhibition of [H]MRT-92 binding is right shifted (3- to 100-fold) for the S387A, L325F, and D473H mutants but did not differ from that of WT receptor for the other mutants. The ability of SANT-1 to inhibit [H]MRT-92 binding to V329F and T466F mutants is abolished, and it is severely impaired for L325F, I408F, and M525G mutants (4- to 140-fold drop of the IC50), but is not modified for the S387A mutant. Taken together, these data confirm our docking hypothesis that MRT-92-binding mode differs from that of either Taladegib or SANT-1 by simultaneously occupying binding sites 1 and 2.
Medlife has not independently confirmed the accuracy of these methods. They are for reference only.