Figure 1. IPI-926 is significantly more potent than cyclopamine in cell based assays.

IPI-926 inhibits Shh-induced Gli-Luciferase activity with an EC₅₀ value of 9 nM in NIH-3T3 cells (A) and 2 nM in HEPM cells (B) compared to cyclopamine which had an EC₅₀ value of 315 nM in NIH-3T3 cells (A) and 59 nM in HEPM cells (B) (N = 3). (C) IPI-926 inhibits alkaline phosphatase production resulting from Shh-induced C3H10T1/2 cell differentiation with an EC₅₀ value of 12 nM compared to 399 nM for cyclopamine (N = 2). (D) IPI-926 inhibits the binding of BODIPY-labeled cyclopamine to C3H10T1/2 cells overexpressing wild-type human Smo with an EC₅₀ value of 1 nM compared to an EC₅₀ value of 114 nM for unlabeled cyclopamine.