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Dasatinib (BMS-354825)

现货
Catalog No.
A3017
Src和BCR-Abl抑制剂
组合的产品项目
规格价格库存 数量
10mM (in 1mL DMSO)
¥ 550.00
现货
100mg
¥ 500.00
现货
500mg
¥ 950.00
现货

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Background

Dasatinib is a small-molecule inhibitor of both the Src and Bcr-Abl tyrosine kinases with IC50 values of 0.5 nM and 1 nM.  The oncogenic tyrosine kinase Bcr-Abl, plays a critical role in the pathogenesis of CML (chronic myelogenous leukemia). In most CML patients, the kinase domain of Bcr-Abl have mutations that interfere with binding to the first Abl kinase inhibitor, but Dasatinib bind more efficiently to these Abl kinase mutations and thus more effective than imatinib in inhibiting the proliferation cells with wild-type Bcr-Abl or Bcr-Abl mutants.

References
1. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. S Nam, D Kim, JQ Cheng, S Zhang, JH Lee, R Buettner. Cancer Research. 2005
2. Dasatinib (BMS-354825) selectively induces apoptosis in lung cancer cells dependent on epidermal growth factor receptor signaling for survival. L Song, M Morris, T Bagui, FY Lee, R Jove, EB Haura . Cancer Research. 2006

文献引用

1.White SM, Avantaggiati ML, et al. "YAP/TAZ Inhibition Induces Metabolic and Signaling Rewiring Resulting in Targetable Vulnerabilities in NF2-Deficient Tumor Cells." Dev Cell. 2019 May 6;49(3):425-443.e9. PMID:31063758
2.Alzubi MA, Turner TH, et al. "Separation of breast cancer and organ microenvironment transcriptomes in metastases." Breast Cancer Res. 2019 Mar 6;21(1):36. PMID:30841919
3.Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID:30038713
4.Singleton KR, Crawford L, et al. "Melanoma Therapeutic Strategies that Select against Resistance by Exploiting MYC-Driven Evolutionary Convergence." Cell Rep. 2017 Dec 5;21(10):2796-2812. PMID:29212027
5. Qian XL, Zhang J, et al."Dasatinib inhibits c-src phosphorylation and prevents the proliferation of Triple-Negative Breast Cancer (TNBC) cells which overexpress Syndecan-Binding Protein (SDCBP)." PLoS One. 2017 Jan 31;12(1):e0171169. PMID:28141839

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt488.01
Cas No.302962-49-8
FormulaC22H26ClN7O2S
SynonymsSprycel,dasatinibum,Dasatinib,BMS-354825, BMS354825, BMS 354825
Solubility≥24.4mg/mL in DMSO
Chemical NameN-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide
SDFDownload SDF
Canonical SMILESCC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=NC(=NC(=C3)N4CCN(CC4)CCO)C
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。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。

试验操作

细胞实验[1]:

细胞系

DU-145和LNCaP细胞

溶解方法

在DMSO中的溶解度>10 mM。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

100 nM, 抑制FAK磷酸化:6 h;减少细胞接触:24 h

应用

在DU-145细胞中,dasatinib几乎完全阻止p-FAK在Tyr576/577位点的磷酸化水平,而在LNCaP细胞中检测不到p-FAK,尽管两个细胞系中总FAK蛋白的表达水平相似。100 nmol/L的dasatinib处理24小时后对细胞活力和总细胞数没有影响,而在48和72小时后观察到G1期停滞,从而部分抑制细胞增殖。在DU-145细胞中,细胞接触显著减少,可能与p-FAK和p-p130CAS水平的下降相关。

动物实验[2]:

动物模型

Pdx1-Cre、Z/EGFP、LSL-Kras G12D/+、LSL-Trp53R172H/+小鼠

剂量

10 mg/kg/d;口服给药

应用

不同治疗组之间的存活率没有显著差异。对照组动物的中位生存时间是131天,从6周龄和10周龄开始用dasatinib治疗的动物中中位生存时间分别为127天和130天。小鼠中肿瘤负荷的分析表明,所有小鼠均有侵入的PDAC。然而,在dasatinib治疗动物中,有肿瘤转移的小鼠数量显著减少。对照动物中肿瘤转移发生率为61.1%,而从6周龄和10周龄开始dasatinib治疗的动物中,肿瘤转移发生率分别为26.7%和23.1%。

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] Nam S, Kim D, Cheng J Q, et al. Action of the Src family kinase inhibitor, dasatinib (BMS-354825), on human prostate cancer cells. Cancer research, 2005, 65(20): 9185-9189.

[2] Morton J P, Karim S A, Graham K, et al. Dasatinib inhibits the development of metastases in a mouse model of pancreatic ductal adenocarcinoma. Gastroenterology, 2010, 139(1): 292-303.

生物活性

Targets Abl Src c-Kit (WT)/c-Kit (D816V)      
IC50 0.6 nM 0.8 nM 79 nM/37 nM      

质量控制

化学结构

Dasatinib (anhydrous)

相关生物数据

Dasatinib
293T cells were transfected with wild type c-Abl, or the gatekeeper mutation for c-Abl T315I. Transfected cells were untreated or treated with 5mM H2O2 for 10 min with or without pretreatment with 20 nM dasatinib for 30min. Whole cell lysates were resolved using SDS-PAGE and analyzed for PKCδpY64, pY155, and pY311. An asterisk denotes the band representing PKCδpY155. Blots were stripped and probed for total PKCδ, total c-Src, total c-Abl, andactin.

相关生物数据

Dasatinib

相关生物数据

Dasatinib

相关生物数据

Dasatinib

相关生物数据

Dasatinib