Hh signaling inhibitor Q29 is a small molecule inhibitor of hedgehog pathway with IC50 of 1.33 uM in Gli-luciferase assay, binds to the cysteine-rich domain (CRD) of smoothened (SMO) and blocks its cholesterylation.
Q29 dose dependently decreases the protein and mRNA levels of endogenous Gli1 in NIH 3T3 cells.
Q29 inhibits Gli-luciferase activities stimulated by cholesterol or 20(S)-OHC (IC50 of 3.13 uM for cholesterol and 2.02 uM for 20(S)-OHC, suppresses ciliary accumulation of SMO induced by Shh-N.
Q29 inhibits SMO through acting on the CRD, does not bind to SMO-7TM.
Q29 dose dependently decreases cholesterylation of SMO in both wild-type (WT) and Ptch1 KO cells.
Q29 (1-10 uM) dose dependently inhibits the growth of medulloblastoma cells isolated from Ptch1+/−P53−/− mice in vitro.
Q29 (90 mg/kg twice daily) inhibits the growth of Ptch1+/−P53−/− medulloblastoma allograft tumor in vivo, exhibits a synergistic inhibitory effect with vismodegib.