MK-4101

Description: MK-4101 is a novel, potent and selective SMO inhibitor/antagonist of the Hedgehog (Hh) signaling pathway. MK-401 has the potential for the treatment of medulloblastoma and BCC (Basal Cell Carcinoma) as it is highly active against these cells. MK-4101 inhibits Hh signaling both in a reporter gene assay in an engineered mouse cell line (Gli Luc) with IC50 of 1.5 uM and in human KYSE180 oesophageal cancer cells with an IC50 of 1 uM. Furthermore, MK-4101 displaced a fluorescently-labeled cyclopamine derivative from 293 cells expressing recombinant human SMO with an IC50 of 1.1 uM. MK-4101 arrests cells in G1 and G2 phases. Beside antitumor activity on transplanted tumors, MK-4101 was highly efficacious against primary medulloblastoma and BCC developing in the cerebellum and skin of Ptch1(+/-) mice.

References: Mol Cancer Ther. 2016 Jun; 15(6):1177-89.