LDK378
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
LDK378是一种高效的间变性淋巴瘤激酶(ALK)抑制剂，半数最大抑制浓度IC50为200 pM，ALK是一种属于胰岛素受体超家族的受体酪氨酸激酶。LDK378对一组其他激酶也具有中到高度的抑制作用，其中IC50低于100 nM的仅有三种激酶，包括IGF-1R (8 nM)、 InsR (7 nM)和STK22D (23 nM)。前期研究中发现，LDK378抑制转染NPM-ALK融合基因的Ba/F3细胞，以及带有NPM-ALK融合基因的Karpas 299人类非Hodgkin’s Ki阳性大细胞淋巴瘤的增殖，IC50分别为22.8 nM和26 nM。
参考文献：
[1]Chen J, Jiang C, Wang S. LDK378: a promising anaplastic lymphoma kinase (ALK) inhibitor. J Med Chem. 2013 Jul 25;56(14):5673-4. doi: 10.1021/jm401005u. Epub 2013 Jul 9.
[2]Marsilje TH, Pei W, Chen B, Lu W, Uno T, Jin Y, Jiang T, Kim S, Li N, Warmuth M, Sarkisova Y, Sun F, Steffy A, Pferdekamper AC, Li AG, Joseph SB, Kim Y, Liu B, Tuntland T, Cui X, Gray NS, Steensma R, Wan Y, Jiang J, Chopiuk G, Li J, Gordon WP, Richmond W, Johnson K, Chang J, Groessl T, He YQ, Phimister A, Aycinena A, Lee CC, Bursulaya B, Karanewsky DS, Seidel HM, Harris JL, Michellys PY. 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 Jul 25;56(14):5675-90. doi: 10.1021/jm400402q. Epub 2013 Jun 26.
| Storage | Store at -20°C |
| M.Wt | 558.14 |
| Cas No. | 1032900-25-6 |
| Formula | C28H36ClN5O3S |
| Synonyms | LDK 378;LDK-378;Ceritinib |
| Solubility | insoluble in H2O; ≥13.95 mg/mL in DMSO; ≥4.62 mg/mL in EtOH with gentle warming |
| Chemical Name | 5-chloro-2-N-(5-methyl-4-piperidin-4-yl-2-propan-2-yloxyphenyl)-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine |
| SDF | Download SDF |
| Canonical SMILES | CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验[1]: | |
|
细胞系 |
鼠前B细胞系Ba / F3，人类细胞系Karpas290 |
|
溶解方法 |
该化合物在DMSO里面的溶解度>14mg/mL。为了获得更高的浓度，可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。 |
|
反应条件 |
10 到50 nM |
|
应用 |
LDK378在Ba / F3-NPM-ALK和Karpas290细胞中表现出很强的抗增殖活性。 |
| 动物实验[2]: | |
|
动物模型 |
2周龄的Karpas 299（皮下注射具有NPM-ALK融合的Karpas 299细胞）和H2228（皮下注射具有EML4-ALK融合的H2228细胞）大鼠异种移植模型 |
|
剂量 |
每天6.25,12.5,25,50mg / kg;连续14天 |
|
应用 |
在Karpas299研究中，LDK378诱导剂量依赖性的生长抑制和肿瘤消退。在H2228研究中，LDK378在25mg / kg诱导剂量依赖性的生长抑制和完全肿瘤消退。在两种模型中，LDK378耐受性良好，并且在所有测试剂量下均未观察到体重下降。 |
|
注意事项 |
请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。 |
|
References: [1]. Marsilje TH., 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, Jun 6. | |
| Description | LDK378是一种强效的ALK抑制剂，IC50值为0.2 nM，比对IGF-1R和InsR的选择性分别高40倍和35倍。 | |||||
| 靶点 | ALK | |||||
| IC50 | 0.2 nM | |||||
质量控制和MSDS
- 批次:
化学结构
相关生物数据
