Table 1.

Inhibition of SAG activity

CompoundShh-LIGHT2, nMSmoA1-LIGHT2, nMPtch1−/−, nMSAG inhibitionKD, nMPA-cyc competition
SANT-1 20  30  2060-fold1.2 +
SANT-2 30  70  5010-fold 12 +
SANT-3100  80  8010-fold 44 +
SANT-4200 300 30010-fold 71 +
  • * IC50 in the Shh-LIGHT2 assay using ShhNp as described.

  • IC50 in the SmoA1-LIGHT2 assay as described.

  • IC50 in cells derived from Ptch1−/− embryos, using β-galatosidase activity as a measure of pathway activation.

  • § Attenuation of SAG activity in Shh-LIGHT2 cells.

  • Apparent KD determined by the BODIPY-cyclopamine binding competition assay.

  • Ability to compete the crosslinking of Smo-Myc3 by PA-cyclopamine.