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.

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

MK-4101 在工程小鼠细胞株 (Gli_Luc) 的报告基因测定中以及在人类KYSE180食管癌细胞中均能抑制Hh信号传导，其半抑制浓度(IC50) 分别为1.5 μM和1 μM。此外，MK-4101 还能以IC50 = 1.1 μM的浓度从表达重组人SMO的293细胞中置换出荧光标记的cyclopamine衍生物。MK-4101可导致细胞在G1和G2期阻滞[1]。

MK-4101通过抑制肿瘤细胞的增殖和诱导大量的凋亡，展现出强大的抗肿瘤活性。针对Ptch1+/-小鼠大脑皮质和皮肤中发展的原发性髓母细胞瘤和基底细胞癌(BCC)特别有效。MK-4101的药代动力学显示，该化合物可通过口服给药，体现出良好的生物利用度（F ≥ 87%），在小鼠和大鼠中展现出低至中等的血浆清除率。此外，它吸收良好，主要通过胆汁排泄[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)