MK-4101 是一种Smo拮抗剂 ，对 293 细胞的IC50为 1.1 μM。它也是一种hedgehog信号通路的有效抑制剂 ，对小鼠细胞和KYSE180 食管癌细胞的IC50分别为 1.5 μM和 1 μM。它能抗肿瘤，抑制肿瘤细胞增殖并诱导细胞凋亡。

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.

MK-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[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)

935273-79-3

C24H24F5N5O

493.482

Ethanol:60 mg/mL (121.6 mM)
H2O:<1 mgml
DMSO:92 mg/mL (186.4 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years