Ceritinib (LDK378)

目录号:S7083

Ceritinib (LDK378) Chemical Structure

Molecular Weight(MW): 558.14

Ceritinib (LDK378)是一种有效的ALK抑制剂,在无细胞试验中IC50为0.2 nM,与作用于IGF-1R和InsR相比,选择性分别高40和35倍。Phase 3。

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RMB 3868.47 现货
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客户使用Selleck该产品发表文献19篇:

产品安全说明书

ALK抑制剂选择性比较

生物活性

产品描述 Ceritinib (LDK378)是一种有效的ALK抑制剂,在无细胞试验中IC50为0.2 nM,与作用于IGF-1R和InsR相比,选择性分别高40和35倍。Phase 3。
特性 不与c-Met交叉反应,对体内葡萄糖稳态比TAE684效果好,有效作用于 Crizotinib复发的肿瘤。
靶点
ALK [1]
(Cell-free assay)
Insulin Receptor [1]
(Cell-free assay)
IGF-1R [1]
(Cell-free assay)
0.2 nM 7 nM 8 nM
体外研究

LDK378作用于Ba/F3-NPM-ALK和Karpas290细胞,具有显著的抗增殖活性,IC50分别为26.0 nM 和 22.8 nM,作用于Ba/F3-Tel-InsR 和Ba/F3-WT细胞,IC50分别为319.5 nM 和 2477 nM。[1]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
Parental(+IL3) NWrQdINrT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFK0[GQ4OiCq NFPvSGVFVVOR MmfWTWM2OD1zNUi2JOKyKDF5MzDuUS=> NGTrc2QzPTd2OUCzOC=>
WT 70 MVTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MofnO|IhcA>? MWLEUXNQ M{nZSmlEPTB;MkGgxtEhQCCwTR?= Mn33NlU4PDlyM{S=
G1128S 1022 MnPCS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NITxTXE4OiCq NYXMfpR6TE2VTx?= MXfJR|UxRTFyMjFCtUA{QCCwTR?= M1zze|I2PzR7MEO0
C1156F 1293 NETSbVlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MnzaO|IhcA>? NV3hRo1NTE2VTx?= MU\JR|UxRTJzNzFCtUAyOTVibl2= NXT6RXNlOjV5NEmwN|Q>
I1171N 519 NIKxbnlIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWG3NkBp MkHsSG1UVw>? M3[xNWlEPTB;MUi3JOKyKDh5IH7N MXyyOVc1QTB|NB?=
I1171T 445 MlrIS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Ml7sO|IhcA>? M3LGWmROW09? M4XBdmlEPTB;OEKgxtEhOTJibl2= MkHjNlU4PDlyM{S=
F1174I 184 MX7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M1z5TVczKGh? NXi1fmlJTE2VTx?= NIXTNWlKSzVyPUGzJOKyKDBwMTDuUS=> NFHKOGMzPTd2OUCzOC=>
N1178H 169 MnzMS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MUK3NkBp M4XUbWROW09? Mo[zTWM2OD12MjFCtUA3KG6P NVLJT2VoOjV5NEmwN|Q>
E1210K 748 MlfNS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MonJO|IhcA>? NECzZ4hFVVOR NI\RSXNKSzVyPUG4O{DDuSB6NDDuUS=> NHXBVWIzPTd2OUCzOC=>
C1156F/D1203N 2809 NWPkfnh3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NFXPVYk4OiCq MmrNSG1UVw>? NX71SWpYUUN3ME2yOVQhyrFiOUmgcm0> MUOyOVc1QTB|NB?=
Ba/F3 NA WT M1v1OWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MX[3NkBp NWP3VY9mUUN3ME2wMlAzOCEQvF2= MXSyOVczPzRyMB?=
Ba/F3 NA C1156Y NIHQUXVIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWXvcZZpPzJiaB?= NXzzOoFyUUN3ME2wMlA4OSEQvF2= M2flfFI2PzJ5NECw
Ba/F3 NA L1196M MVrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NFHLXZk4OiCq NEDoc4tKSzVyPUCuNFQzKM7:TR?= MmnaNlU4Ojd2MEC=
Ba/F3 NA L1152R NFz5b25Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NHjvfXI4OiCq MYPJR|UxRTBwMki4JO69VQ>? NWq0O3lFOjV5Mke0NFA>
Ba/F3 NA G1202R Mne3S5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NWOyUnpoPzJiaB?= NHroV3lKSzVyPUCuNlc4KM7:TR?= Mo[wNlU4Ojd2MEC=
Ba/F3 NA G1269A MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? Ml7hO|IhcA>? NHjBOodKSzVyPUCuNFE6KM7:TR?= MUiyOVczPzRyMB?=
Ba/F3 NA S1206Y MlXDS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MX[3NkBp NHTrTlFKSzVyPUCuNFM4KM7:TR?= MlfaNlU4Ojd2MEC=
Ba/F3 EA WT NFLRPGpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MX63NkBp NUXl[3pkUUN3ME2wMlAzOSEQvF2= M1XhZlI2PzJ5NECw
Ba/F3 EA C1156Y MVPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MYq3NkBp NGTSc|FKSzVyPUCuNFI3KM7:TR?= NXLUZWNwOjV5Mke0NFA>
Ba/F3 EA L1196M MmXJS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MWG3NkBp MVrJR|UxRTBwMEG5JO69VQ>? M3fnXlI2PzJ5NECw
Ba/F3 EA L1152R NELjb49Iem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NXjW[2pxPzJiaB?= M2HyS2lEPTB;MD6wPVkh|ryP MkLNNlU4Ojd2MEC=
Ba/F3 EA G1202R NHH0OGNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= M13pdFczKGh? MWjJR|UxRTBwNE[3JO69VQ>? MmjtNlU4Ojd2MEC=
Ba/F3 EA G1269A NXv1U3F4T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NXHINHdsPzJiaB?= M4G5NGlEPTB;MD6wN|Mh|ryP MmrMNlU4Ojd2MEC=
Ba/F3 EA S1206Y MnLQS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NVz1[4VPPzJiaB?= MUDJR|UxRTBwMEO4JO69VQ>? MYKyOVczPzRyMB?=

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-ALK / ALK / p-AKT / AKT / p-ERK / ERK; 

PubMed: 28425916     


Inhibition of ALK autophosphorylation and downstream signaling by ceritinib, crizotinib and PF06463922 in NB-1 cells. Cells were harvested after treatment for 4 hr with the indicated compounds at different concentrations. Whole cell lysates were analyzed by Western blotting to detect the levels of ALK, AKT and ERK proteins and their phosphorylation.

pROS1 / ROS1 / pSTAT3 / STAT3 ; 

PubMed: 25351743     


Inhibition of phospho-ROS1 by various ALK inhibitors in Ba/F3 models. CD74-ROS1 expressing Ba/F3 cells were exposed to increasing concentrations of crizotinib, ceritinib, AP26113, or ASP3026 for 3 h. Cell lysates were immunoblotted to detect the indicated proteins.

28425916 25351743
Growth inhibition assay
Cell viability; 

PubMed: 29067644     


The effects of ceritinib treatment on cell viability in ARMS and ERMS cell lines. Cells were treated with 0-5 μM ceritinib for 72 h (Rh30, RD), 120 h (Rh41), or 144 h (Rh18, Aska) and cell viability was assessed. The y-axis represents relative cell viability compared to non-treated cells (control). Effects on cell viability were determined in triplicate. Values are presented as mean ± SD. Dotted line represents the IC50-value. The human synovial sarcoma cell line Aska with constitutive ALK phosphorylation was used as a positive control.

29067644
体内研究 LDK378 用于降低形成反应代谢的可能性,在肝微粒体几乎检测不到谷胱甘肽(GSH)加合物的水平(<1%)。LDK378具有相对良好的代谢稳定性,中度抑制CYP3A4(Midazolam底物)和抑制hERG。LDK378处理动物,与肝脏血流量相比,具有低的血浆清除率(小鼠,大鼠,狗和猴),处理小鼠,大鼠,狗和猴的口服生物利用度都在55%以上。LDK378 处理Karpas299 和H2228 大鼠移植瘤模型,抑制肿瘤生长,诱导肿瘤衰退,这种作用具有剂量依赖性,体重没有降低。LDK378处理小鼠,剂量高达100 mg/kg,对胰岛素水平或血浆葡萄糖的利用无影响。[1]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
+ 展开

激酶分析:

所有激酶使用杆状病毒表达技术表达为组氨酸或GST标签的融合蛋白,除了在大肠杆菌中产生的未标记的ERK2。在LabChip迁移实验中测量激酶活性。实验在30°C下进行60分钟。在有或无LDK378存在时,通过线性进展曲线,获得LDK378对酶活性的作用效果。
细胞实验:[1]
+ 展开
  • Cell lines: Ba/F3-NPM-ALK, Ba/F3-Tel-InsR, Ba/F3-WT, Karpas299 细胞
  • Concentrations: ~100 μM
  • Incubation Time: 2-3 天
  • Method: 表达荧光素酶的细胞与连续稀释的LDK378 或 DMSO 温育2-3天。荧光素酶的表达用来衡量细胞增殖/存活,使用Bright-Glo萤光素酶检测系统来评估。使用 XLFit软件获得 IC50值。
    (Only for Reference)
动物实验:[1]
+ 展开
  • Animal Models: 携带 Karpas299/H2228肿瘤的 RNU裸鼠
  • Formulation: LDK378 (磷酸盐形式)在 0.5% 甲基纤维素/0.5% Tween 80中制备
  • Dosages: ~50 mg/kg
  • Administration: 口服饲喂
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 20 mg/mL warmed (35.83 mM)
Ethanol 3 mg/mL (5.37 mM)
Water Insoluble

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 558.14
化学式

C28H36ClN5O3S

CAS号 1032900-25-6
储存条件 powder
in solvent
别名 N/A

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT02450903 Completed Non-Small-Cell Lung Cancer Novartis Pharmaceuticals|Novartis August 21 2015 Phase 2
NCT02276027 Recruiting Adenocarcinoma Lung Cancer; Squamous Cell Lung Carcinoma Novartis Pharmaceuticals|Novartis January 20 2015 Phase 2
NCT02040870 Completed Non-Small Cell Lung Cancer Novartis Pharmaceuticals|Novartis March 7 2014 Phase 1|Phase 2
NCT01950481 Completed Normal Hepatic Function|Impaired Hepatic Function Novartis Pharmaceuticals|Novartis January 2014 Phase 1
NCT01772797 Completed Anaplastic Lymphoma Kinase (ALK)|Non-small Cell Lung Cancer Novartis Pharmaceuticals|Novartis June 2013 Phase 1
NCT01685060 Completed Non-Small Cell Lung Cancer Novartis Pharmaceuticals|Novartis November 26 2012 Phase 2

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操作手册

如果有其他问题,请给我们留言。

  • * 必填项

常见问题及建议解决方法

  • 问题 1:

    how to reconstitute the inhibitor for oral administration to mice?

  • 回答:

    You can resuspend LDK378 in 30% PEG400/0.5% Tween 80/5% propylene glycol and use the suspension for oral gavage feeding.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID