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Dasatinib (BMS-354825)Src和BCR-Abl抑制剂

Dasatinib (BMS-354825)

产品编号:A3017
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10mM (in 1mL DMSO) ¥550.00 现货
100mg ¥500.00 现货
500mg ¥950.00 10-15 工作日发货

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Sample solution is provided at 25 µL, 10mM.

引用文献

1.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
2.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
3. 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

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

Dasatinib (BMS-354825) Dilution Calculator

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化学性质

CAS号 302962-49-8 SDF Download SDF
别名 Sprycel,dasatinibum,Dasatinib,BMS-354825, BMS354825, BMS 354825
化学名 N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide
SMILES CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=NC(=NC(=C3)N4CCN(CC4)CCO)C
分子式 C22H26ClN7O2S 分子量 488.01
溶解度 ≥24.4mg/mL in DMSO 储存条件 Store at -20°C
物理性状 A solid 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。

生物活性

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

实验操作

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.

研究更新

1. Major molecular response during the first year of dasatinib, imatinib or nilotinib treatment for newly diagnosed chronic myeloid leukemia: a network meta-analysis. Cancer Treat Rev. 2014 Mar;40(2):285-92. doi: 10.1016/j.ctrv.2013.09.004. Epub 2013 Sep 17.
Abstract
Randomized trials have been conducted to compare the effects of dasatinib, nilotinib and imatinib in the treatment of newly diagnosed chronic myrloid leukemia in the chronic phase.
2. Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial. Lancet Oncol. 2013 Dec;14(13):1307-16. doi: 10.1016/S1470-2045(13)70479-0. Epub 2013 Nov 8.
Abstract
Dasatinib is an inhibitor of tyrosine kinase including Src kinases that exhibits antitumor activity, affects osteoclasts and synergize with docetaxel. The efficacy of dasatinib alone or with docetaxel has been assessed in chemotherapy-naive men with metastatic castration-resistant prostate cancer.
3. The development of dasatinib as a treatment for chronic myeloid leukemia (CML): from initial studies to application in newly diagnosed patients. J Cancer Res Clin Oncol. 2013 Dec;139(12):1971-84. doi: 10.1007/s00432-013-1488-z. Epub 2013 Aug 13.
Abstract
Dasatinib is a dual Abl/Src TKI that inhibits BCR-ABL with relatively greater potency and show potential immunomodulatory effects. Since it’s been approved to treat CML patients, the development of dasatinib is reviewed.
4. Dasatinib inhibits mammary tumour development in a genetically engineered mouse model. J Pathol. 2013 Aug;230(4):430-40. doi: 10.1002/path.4202.
Abstract
Daily oral administration of dasatinib, an inhibitor of Src family kinases, to mice with breast cancer delays tumor onset and increases overall survival with the occurrence of squamous metaplasis accompanied by down-regulation of ErbB-2 and up-regulation of E-cadherin and β-catenin. Additionally, dasatinib inhibited both migration and invasion of tumour-derived cell lines in vitro.
5. Simultaneous manifestation of pleural effusion and acute renal failure associated with dasatinib: a case report. J Clin Pharm Ther. 2014 Feb;39(1):102-5. doi: 10.1111/jcpt.12107. Epub 2013 Nov 5.
Abstract
Dasatinib is an inhibitor of multiple tyrosine kinases that are used to treat CML and ALL. Although renal failure is a rare side effect of dasatinib, a patient with imatinib-resistant CML has developed both PE and ARF after receiving dastinib.

产品描述

Dasatinib是Src和Bcr-Abl酪氨酸激酶的小分子抑制剂,IC50值分别为0.5 nM和1 nM。致癌酪氨酸激酶Bcr-Abl在慢性髓细胞性白血病(CML)的发病机制中具有重要作用。在大多数CML患者中,Bcr-Abl的激酶结构域含有突变,干扰其与第一类Abl激酶抑制剂的结合,而dasatinib可以更加有效的与这些Abl激酶突变结合,因而比imatinib更有效的抑制含野生型Bcr-Abl或Bcr-Abl突变的细胞的增殖。

参考文献:
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