A nanomolar Smoothened (smo) antagonist that exhibits 2.3- and 6-fold weaker biological activity than SANT-1 (Cat. No.
559303), respectively, in antagonizing ShhNp- and SAG-stimulated hedgehog pathway activation in HEK 293-based (Shh-LIGHT2) reporter assays. Competitive binding studies show full replacement of Smo-bound cyclopamine (Cat. No.
239803) by SANT-1 and SANT-2 (K
i = 2.4 and 8.4 nM, respectively), while SANT-1 and SANT-2 are shown to compete against Smo-bound SAG-1.3 (Cat. Nos.
566660 &
566661) in an allosteric manner and that only SANT-2, but not SANT-1, is able to completely compete off bound SAG-1.3 (100% vs. 40% replacement by the respective compound at 10 μM).
