Dasatinib

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Chemical Structure| 302962-49-8 同义名 : BMS-354825;Sprycel
CAS号 : 302962-49-8
货号 : A355193
分子式 : C22H26ClN7O2S
纯度 : 98%
分子量 : 488.005
MDL号 : MFCD11046566
存储条件：

Pure form Sealed in dry,Store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 120 mg/mL(245.9 mM)，配合低频超声助溶，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：

4% DMSO+30% PEG 300+5% Tween 80+water 5 mg/mL

生物活性
靶点

  • c-Kit

    c-Kit (wt), IC50:79 nM

    c-Kit (D816V), IC50:37 nM

  • Src

    Src, IC50:0.8 nM

  • Abl

    Abl, IC50:0.6 nM
描述 The oncogenic tyrosine kinase Bcr-Abl plays a central role in the pathogenesis of chronic myelogenous leukemia, thus makes it as the therapy drug target. However, it is demonstrated that the mutations of Bcr-Abl kinase have been the most common mechanism of drug resistance, such as imatinib. Dasatinib is a potent Bcr-Abl inhibitor with IC50 values of 0.6 nM, 0.8 nM and 2.8 nM for Abl, Src and Lyn, as well as IC50 values ranging in 0.1 - 1.8 nM for different Abl mutations except the T315l mutation (measured by in vitro kinase assays). Consistent with the results from the kinase assays, dasatinib showed more potent growth inhibition in Ba/F3 expressing various Abl mutations with a narrow range of low nanomoles, as well as the inhibition on Bcr-Abl tyrosine phosphorylation with IC50 values below 10 nM，compared with imatinib[1] Oral administration of Dasatinib at dose of 5 or 20 mg/kg robustly reduced the CML phenotype and included stem and progenitor populations in tetracycline-controlled transgenic BCR-ABL mice, more potent than imatinib[2]. Dasatinib also showed inhibitory activity against Lck, yes and c-kit with IC50 values of 0.4 nM, 0.5 nM and 5 nM, respectively, and possessed cellular antiproliferative activities on tumor cells of different origins, most potent to CML cell line K562 with IC50 < 1 nM. Oral treatment with Dasatinib, at dose of both 5 mg/kg and 50mg/kg on a 5 day on and 2 day off schedule for two cycles, demonstrated complete tumor regressions in a K562 xenograft model of CML[3].
作用机制 Dasatinib is a ATP-competitive inhibitor of both Abl and Src[4].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
697 Growth Inhibition Assay IC50=0.19987 μM SANGER
8-MG-BA Growth Inhibition Assay IC50=0.15458 μM SANGER
A101D Growth Inhibition Assay IC50=1.03043 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.05mL

0.41mL

0.20mL

10.25mL

2.05mL

1.02mL

20.49mL

4.10mL

2.05mL
参考文献

[1]O'Hare T, Walters DK, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5.

[2]Dasatinib Exerts Differential Effects on Normal and BCR-ABL Positive Hematopoietic Cells in a Transgenic Mouse Model of Chronic Phase-CML

[3]Lombardo LJ, Lee FY, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004 Dec 30;47(27):6658-61.

[4]Reddy EP, Aggarwal AK, et al. The ins and outs of bcr-abl inhibition. Genes Cancer. 2012 May;3(5-6):447-54.

[5]Luo FR, Yang Z, et al. Dasatinib (BMS-354825) pharmacokinetics and pharmacodynamic biomarkers in animal models predict optimal clinical exposure. Clin Cancer Res. 2006 Dec 1;12(23):7180-6.

[6] Pharmacokinetics of dasatinib