Ensartinib (X-396) is a potent and orally active dual ALK/MET inhibitor for the treatment of ALK-positive non-small cell lung cancer (NSCLC).

ALK:13.4 nM

Ensartinib 是一种高效的 ALK 抑制剂，在多种表达 EML4-ALK 融合基因的非小细胞肺癌细胞中表现出显著的抗增殖活性。例如，在 H3122 细胞中，Ensartinib（IC₅₀ = 13.4 nM）显著抑制细胞生长，并诱导 PARP 切割和细胞凋亡。此外，Ensartinib还可抑制 ALK 自磷酸化以及下游 AKT 和 ERK 的激活，提示其对 ALK 信号通路具有有效抑制作用[1]。

在 H3122 异种移植小鼠模型中，Ensartinib（50 或 100 mg/kg，口服灌胃，每日一次，连续 14 天）可显著抑制肿瘤生长（p < 0.001），且在高剂量组（100 mg/kg）观察到部分肿瘤完全消退。Ensartinib 在体内具有良好的口服生物利用度和靶向 ALK 的有效性，且毒性较低[1]。

For viability experiments, cells are seeded in 96-well plates at 25%-33% confluency and exposed to drugs.The human lung adenocarcinoma cell lines H3122 and H2228 are treated with Ensartinib (10, 30, 100, 300 and 1000 nM). SUDHL-1 lymphoma cells are treated with Ensartinib (5, 10, 30, 100 and 300 nM). SY5Y neuroblastoma cells are treated with Ensartinib (30, 100, 300 and 1000 nM). At 72 hours post Ensartinib addition, Cell Titer Blue Reagent is added and fluorescence is measured on a Spectramax spectrophotometer. All experimental points are set up in hextuplicate replicates and are performed at least two independent times. IC50s are calculated using GraphPad Prism version 5 for Windows. The curves are fit using a nonlinear regression model with a log (inhibitor) vs. response formula[1].