MK-4101, an effective inhibitor of the Hedgehog pathway, has anti-tumor activity through the induction of extensive apoptosis and inhibition of proliferation in tumor cells.

KYSE180 oesophageal cancer cells:1 µM (IC50), Mouse cells:1.5 µM (IC50), HEK293 cells:1.1 µM (IC50)

MK-4101 inhibits Hh signaling with an IC50 of 1.5 μM in a reporter gene assay (Gli_Luc) in an engineered mouse cell line and 1 μM in human KYSE180 esophageal cancer cells. It displaces a fluorescently-labeled cyclopamine derivative from 293 cells expressing recombinant human SMO with an IC50 of 1.1 μM. MK-4101 arrests cells in G1 and G2 phases[1].

MK-4101 has robust antitumor activity through the inhibition of proliferation and induction of extensive apoptosis in tumor cells. MK-4101 is highly efficacious against primary medulloblastoma and basal cell carcinoma(BCC) developing in the cerebellum and skin of Ptch1+/- mice. Pharmacokinetics of MK-4101 shows that it could be administered orally, showing a good bioavailability (F ≥ 87 %) with low-to-moderate plasma clearance in mice and rats. Moreover, it was well absorbed, and mainly excreted into the bile[1].

Luciferase assays: After various compound treatments, cells are lysed in luciferase lysis buffer and assayed for luciferase activity using the ONE-Glo luciferase assay system. All luciferase activities are normalized to protein concentration determined by Bradford assay.

BCC cells are treated with MK-4101(10 μM) for 72 h and cell cycle is analyzed by FACS monitoring EdU incorporation. (Only for Reference)