LY2940680 inhibits cancer growth in cell lines containing a mutation in the gene encoding Smoothened that researchers had previously observed in patient with cancer who developed resistance to vismodegib.
In vivo
LY2940680 has excellent pharmacokinetic properties in rodent and non-rodent species. LY2940680 administrated orally treats Ptch p53 transgenic mice which spontaneously develop medulloblastoma, produces remarkable efficacy and significantly improves their survival. LY2940680 reveals rapid kinetics of anti-tumor activity through magnetic resonance imaging of these mice, and LY2940680 induces Caspase-3 activity and reduces proliferation by immunohistochemistry analysis of medulloblastoma tumors. LY2940680 inhibits Hh regulated gene expression in the subcutaneous xenograft tumor stroma and produces significant anti-tumor activity.
