MK-4101 (C09-0967-606)

InformationMK-4101, a potent inhibitor of theHedgehogpathway, shows anti-tumor activity through the inhibition of proliferation and induction of extensive apoptosis in tumor cells.TargetsSMOIn vitroMK-4101 inhibits Hh signaling both in a reporter gene assay in an engineered mouse cell line (Gli_Luc) with IC50 = 1.5 µM and in human KYSE180 oesophageal cancer cells with an IC50 = 1 µM. Furthermore, MK-4101 displaced a fluorescently-labeled cyclopamine derivative from 293 cells expressing recombinant human SMO with an IC50 = 1.1 µM. MK-4101 arrests cells in G1 and G2 phases.In vivoMK-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 medulloblastomaand 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.Cell Research(from reference)Cell lines：BCC(basal cell carcinoma) cells Concentrations：10 μM Incubation Time：72 h. Specification: 0.97 Molecular Formula: C24H24F5N5O Molecular Weight: 493.47 PubChem CID: 16222379 Isomeric SMILES: CN1C(=NN=C1C23CCC(CC2)(CC3)C4=NOC(=N4)C5CC(C5)(F)F)C6=CC=CC=C6C(F)(F)F Related Documents: https://ald-pub-files.oss-cn-shanghai.aliyuncs.com/aladdinsci/pdp/sds/1/M413943-SCI_f57bfa4976319e9651213406c8b5ab9b.pdf