Pipinib is a small molecule Hedgehog signaling inhibitior by selective inhibition of phosphatidylinositol 4-kinase IIIβ (PI4KB, IC50=2.2 uM), inhibits Purmorphamine-induced osteogenesis with IC50 of 0.6 uM.Pipinib inhibited GLI reporter gene activity in Sonic hedgehog (Shh)-LIGHT2 cells (IC50=1.7 uM) and expression of Hh target genes Ptch1 and Gli1 (IC50=3.1 uM and 4.1 uM, respectively).Pipinib does not modulate Hh signaling via SMO.Pipinib is an ATP-competitive inhibitor of PI4KB activity, does not inhibit isoenzymes PI4KA, PI4K2A or PI4K2B up to 50 uM.Pipinib suppresses GLI-mediated transcription and Hh target gene expression by impairing SMO translocation to the cilium.
