Ceritinib (LDK378) is an ALK tyrosine kinase inhibitor (IC50=200 pM) with selective, ATP-competitive, and oral activity. Ceritinib also inhibits IGF-1R, InsR, and STK22D (IC50=8/7/23 nM). Ceritinib has antitumor activity.

STK22D:23 nM (cell free), Insulin receptor:7 nM (cell free), ALK:0.2 nM (cell free), IGF-1R:8 nM (cell free)

方法: 一组肿瘤细胞和多药耐药 (MDR) 细胞用 Ceritinib (0.01-10 µM) 处理 72 h，使用 MTT assay 检测细胞活力。
结果: KB、KBv200、MCF-7、MCF-7/adr、S1、S1-M1-80、HEK293/pcDNA3.1、HEK293/ABCB1 和 HEK293/ABCG2-R2 细胞的 IC50 值分别为1.10±0.31、1.69±0.41、2.15±0.33、2.73±0.46、1.34±0.35、1.69±0.39、1.50±0.37、1.86±0.34、2.84±0.56 µM。根据细胞毒性曲线，超过 85% 的细胞在 0.5 µM Ceritinib 浓度下存活。[1]
方法: 人乳腺癌症细胞系 MDA-MB 453 和 MFM223 用 Ceritinib (10 µM) 处理 15 min-4 h，使用 Western Blot 检测靶点蛋白表达水平。
结果: Ceritinib 处理以时间依赖的方式下调 MDA-MB-453 和 MFM223 细胞中的 AR、ACK1、HER2 和 HER3。[2]

方法: 为检测体内抗肿瘤活性，将 Ceritinib (25 mg/kg，口服给药) 和 paclitaxel (20 mg/kg，腹腔注射) 给药给携带 KBv200 异种移植物的 nude 小鼠，每三天一次，给药四次。
结果: 没有发现分别用生理盐水、Ceritinib 或 paclitaxel 治疗的动物之间肿瘤大小的显著差异。然而，与其他组相比，Ceritinib 和 paclitaxel 联合用药组对肿瘤生长有显著抑制作用。[1]

All kinases were expressed as either Histidine- or GST-tagged fusion proteins using the baculovirus expression technology except for the untagged ERK2 which was produced in E. coli. The kinase activity was measured in the LabChip mobility-shift assay. The assay was performed at 30°C for 60 min. The effect of the compound on the enzymatic activity was obtained from the linear progress curves in the absence and presence of compound and routinely determined from one reading (end point measurement) [1].

Luciferase-expressing cells were incubated with serial dilutions of compounds or DMSO for 2–3 days. Luciferase expression was used as a measure of cell proliferation/survival and was evaluated with the Bright-Glo Luciferase Assay System. IC50 values were generated by using XLFit software [1].

SCID beige mice for crizotinib-resistant H2228 xenograft tumor models, nude mice for MGH006 primary explants and MGH045 cells were randomized into groups of 5, 6 or 8 mice with an average tumor volume of ~150 mm^3 and received Crizotinib or ceritinib daily treatments by oral gavage as indicated in each study. Tumor volumes were determined by using caliper measurements and calculated with the formula (Length × Width × Height)/2 [3].