产品说明书

Ceritinib

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Chemical Structure| 1032900-25-6 同义名 : LDK378
CAS号 : 1032900-25-6
货号 : A126440
分子式 : C28H36ClN5O3S
纯度 : 98%
分子量 : 558.135
MDL号 : MFCD26142648
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(21.5 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 10% DMSO+water 0.5 mg/mL clear

PO 0.5% CMC-Na 50 mg/mL suspension

生物活性
靶点

  • ALK

    ALK, IC50:0.2 nM
描述 ALK (anaplastic lymphoma kinase) is a tyrosine kinase that is constitutively activated in certain cancers, following gene alterations such as chromosomal translocation, amplification or point mutation. Ceritinib is a selective inhibitor of ALK with IC50 value of 0.2nM (measured by enzymatic kinase activity), and less potent to FLT3, IGF-1R, InsR and STK22D with IC50 values of 60nM, 8nM, 7nM and 23nM, respectively, and showed inhibitory activity on celluar kinase in Ba/F3 cells with IC50 values of 40.7nM, 2.2nM, 410nM and 141.8nM for Tel-ALK, EML4-ALK, Tel-IGF-1R and Tel-Ros, respectively. The cell proliferation study showed that Ceritinib exhibited preferential anti-proliferative activity in Ba/F3 cells expressing NPM-ALK (26nM) and in Karpas299 cells with NPM-ALK fusion (22.8nM)[1]. As the second generation of ALK inhibitor, Ceritinib can overcome several crizotinib resistant mutations in non–small cell lung cancers, including in two ALK-rearranged lung cancer cell lines H3122 and H2228, ALK-mutant cells, H3122 CR1 (L1196M), MGH021-4 (G1269A) and MGH045 (L1196M) cells, as well as ALK wild-type (WT) crizotinib-resistant MGH051 cells from patient, and lead inhibition on p-ALK, p-AKT, p-ERK,p-S6 and cell proliferation at much lower dose than Crizotinib. Consistent with the in vitro study, ceritinib showed more potent anti-tumor activity at dose (50mg/kg) lower than crizotinib (100mg/kg) in mice bearing crizotinib-resistant tumors harboring EML4–ALK wild-type, I1171T, or C1156Y mutations[2].
作用机制 Ceritinib is an ATP-competitive ALK inhibitor.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
Ba/F3 EA C1156Y Growth Inhibition Assay 72 h IC50=0.026 μM 25727400
Ba/F3 EA G1202R Growth Inhibition Assay 72 h IC50=0.467 μM 25727400
Ba/F3 EA G1269A Growth Inhibition Assay 72 h IC50=0.033 μM 25727400
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.79mL

0.36mL

0.18mL

8.96mL

1.79mL

0.90mL

17.92mL

3.58mL

1.79mL
参考文献

[1]Marsilje TH, Pei W, et al. Synthesis, structure-activity relationships, and in vivo efficacy of the novel potent and selective anaplastic lymphoma kinase (ALK) inhibitor 5-chloro-N2-(2-isopropoxy-5-methyl-4-(piperidin-4-yl)phenyl)-N4-(2-(isopropylsulfonyl)phenyl)pyrimidine-2,4-diamine (LDK378) currently in phase 1 and phase 2 clinical trials. J Med Chem. 2013;56(14):5675-90.

[2]Friboulet L, Li N, et al. The ALK inhibitor ceritinib overcomes crizotinib resistance in non-small cell lung cancer. Cancer Discov. 2014;4(6):662-673.

[3]Burns MW, Kim ES. Profile of ceritinib in the treatment of ALK+ metastatic non-small-cell lung cancer. Lung Cancer (Auckl). 2015.

[4]van Erp AEM, Hillebrandt-Roeffen MHS, et al. Targeting Anaplastic Lymphoma Kinase (ALK) in Rhabdomyosarcoma (RMS) with the Second-Generation ALK Inhibitor Ceritinib. Target Oncol. 2017 Dec;12(6):815-826.