In vivo studies reveal that animals treated with ShhN in the presence of MRT-83 exhibit normal health similar to control groups, with a notable absence of ShhN-induced upregulation of Patched (Ptc) transcription in the subventricular zone (SVZ), aligning with the compound’s ability to fully inhibit ShhN-mediated effects. Unlike MRT-36, MRT-83 specifically antagonizes the upregulation of Ptc transcription induced by ShhN in the SVZ of the lateral ventricle (LV), indicating its selective inhibition of the Shh pathway^[1].

MRT-83 demonstrates potent antagonist activity against the Sonic Hedgehog (Shh) signaling pathway, with an IC50 of approximately 3 nM in inhibiting ShhN-induced proliferation of rat granule cell precursors (GCPs). It also effectively blocks SAG-induced GCP proliferation and BODIPY-cyclopamine (BC) binding to both human and mouse Smoothened (Smo) receptors in cell-based assays, underscoring its efficacy in disrupting Shh-mediated cellular responses^[1].