SEN450

SEN450 is a selective small molecule antagonist of the Smoothened (SMO) receptor, a key transmembrane protein in the Hedgehog (Hh) signaling pathway. Developed by Siena Biotech, SEN450 was designed to block aberrant Hh pathway activation, which is associated with the development and progression of several malignancies, including glioblastoma, medulloblastoma, and cancers of the pancreas, prostate, and lung. In preclinical studies, SEN450 demonstrated Hedgehog-specific inhibitory activity and showed synergistic anti-tumor effects when combined with the alkylating agent temozolomide in glioblastoma multiforme (GBM) xenograft models. Additionally, related compounds from the same chemical series showed significant tumor volume reduction in medulloblastoma models derived from Patched-mutant mice.