A cell-permeable acylguanidine compound that is shown to block Hh signaling and act as a potent, reversible and high-affinity Smo (Smoothened) antagonist. Displays 20-60 -fold greater potency than Cyclopamine and competitively inhibits bodipy-cyclopamine binding to Smo (IC50 = 4.6 and 14nM in HEK293-hSMO and HEK293-mSMO cells, respectively). Represses ShhN (N-myristoylated Shh) signaling (IC50=15nM for Gli-dependent luciferase activity in Shh-light2 cells) and SAG- induced C3H10T1/2 cell differentiation (IC50=10nM in an alkaline phosphatase activity assay). Inhibits ShhN (3nM) and SAG (10nM)-mediated proliferation of rat cerebellar granule cell precursors (IC50 ~3 and 6nM, respectively).
Formula:C31H30N4O5
Molecular Weight:538.6
Solubility:DMSO (100mg/ml)
Storage and Stability:Lyophilized powder may be stored at -20°C. Stable for 12 months at -20°C. Reconstitute with sterile buffer or dH2O. Aliquot to avoid repeated freezing and thawing. Store at -20°C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
