Figures & data
Figure 1 A schematic diagram showing inhibition of Hedgehog (Hh) signaling by vismodegib.
Notes: The extracellular Hh ligands (Sonic, Indian, or Desert Hh) bind to Patched 1 (Ptch1), relieving the inhibition of Smoothened (SMO) by Ptch1. SMO disrupts the cytoplasmic complex containing the Suppressor of Fused (SUFU)-glioma-associated oncogene homologue (Gli) complex resulting in degradation of Gli3 and translocation of Gli1 and Gli2 to the nucleus to upregulate target genes like Ptch1, Gli1, c-Myc, Bcl2, vascular endothelial growth factor, and cyclin D1. Vismodegib binds to the extracellular domain of SMO, markedly inhibiting the release and translocation of Gli1 and Gli2 to the nucleus.
Abbreviations: Gli, glioma-associated oncogene homologue; Ptch1, patched 1; SHh, sonic hedgehog; SMO, smoothened; SUFU, Suppressor of Fused; VEGF, vascular endothelial growth factor.
Figure 2 Chemical structure of vismodegib.
Note: Structure of vismodegib is courtesy of Genentech.
