产品描述 Dasatinib (BMS-354825) 是一种新型有效的多靶点抑制剂，作用于Abl、Src和 c-Kit，在无细胞试验中IC50分别为 在抑制表达野生型Bcr-Abl或全部Bcr-Abl突变型（除了T315I）的Ba/F3增殖时，Dasatinib效果比Imatinib高很多。与Imatinib相比，Dasatinib呈2倍指数增长效力(约325倍)。Dasatinib有效抑制野生型Abl 激酶和全部突变型（除了T315I）。Dasatinib 直接靶向作用于野生型和突变型Abl激酶域，且抑制自磷酸化和底物磷酸化，这种作用存在浓度依赖性。Dasatinib作用于表达野生型 Bcr-Abl的细胞时，效果比Imatinib高325倍多。[1] TgE骨髓细胞菌落百分数从未处理孔的100% 降低到Dasatinib处理孔的4.12%。 有 Dasatinib存在时, WT 和TgE骨髓细胞形成的菌落百分数明显不同。LMP2A的表达可促进 B 淋巴细胞存活和增殖，而Dasatinib通过靶向作用于Lyn 和/或c-Abl 激酶可抑制以上存活和增殖。[2] Dasatinib 处理一系列甲状腺癌细胞，抑制Src信号, 降低生长速度,使细胞周期停滞，且诱导凋亡。使用剂量不断增加的 Dasatinib (0.019 μM 到 1.25 μM) 处理C643, TPC1, BCPAP, 和 SW1736 细胞3天，抑制50%细胞生长，然而抑制K1细胞系生长则需更高浓度Dasatinib。使用10 nM 或50 nM Dasatinib 处理BCPAP，SW1736 和 K1 细胞，导致G1期细胞提高9-22%，而S期细胞百分数则降低7-18%。[3] MXJR|UxRTBwMECwNFch|ryP MkX5QIEhfGG{Z3X0QUdg[myjbnunJIhzWZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTd7NU[wPFAoRjF5OUW2NFgxRC:jPh?= MoKTWM2OD1yLkCwNUDPxE1? 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Cells were cultured in serum-free culture medium with doxycycline (Dox, 2 g/ml), and western blot was performed at 24 h after dasatinib addition. p27 / p21; PubMed: 20145167 Clin Cancer Res Dasatnib induced cell cycle arrest.Dasatinib induced growth arrest, shown as a cell cycle distribution graph in the lower panel, correlated with increased p27 and p21 levels. Western blotting for levels of p27 and p21 was performed on protein lysates of THP-1 cells treated for 48 hours with indicated doses of dasatinib or DMSO. Detection of actin served as control for comparable protein loading. p-FAK / p-STAT3; PubMed: 23721490 BMC Cancer The effect of dasatinib in cell signalling. Western blot analysis with phosphorylated Src, FAK, Stat3, Akt and MAPK in HCC cell lines after 24hours treatment of dasatinib. The cell lines were arranged according to their IC50to dasatinib. The top three were most sensitive, the bottom 3 were least sensitive. cleaved caspase 3; PubMed: 20145167 Clin Cancer Res Dasatinib induced apoptosis.Dasatinib causes apoptosis in Mo7e-KitD816H cells as detected by cleavage of caspase 3. Whole cell lysates were prepared after 24 hour treatment with dasatinib. Caspase 3 and cleaved capase 3 were analyzed by western blotting. Actin serves as loading control. IC50; PubMed: 23721490 BMC Cancer 9 HCC cell lines were exposed to the dedicated concentrations of dasatinib for 72hours, and IC50was tested by MTS. Results represent the mean ( SD) of three experiments. SRC / Met; PubMed: 26517812 Oncotarget Immunocytochemistry of SRC and Met localization. Cellular localization of SRC and Met following treatment for 48 h with dasatinib, crizotinib or combination in A. LN-18 and B. U373 cells. Scale bar denotes 10 m. Nuclei were visualized by DAPI while SRC and Met were labeled with a fluorescein and Texas-red conjugated secondary antibodies, respectively. F-actin / Actinin-4 / Paxillin; PubMed: 31053734 Nat Commun Conditionally immortalized differentiated podocytes treated for one-hour with 2 M kinase inhibitor were stained for F-actin (phalloidin), -actinin-4, paxillin, and nuclei (Hoechst 33342) to assess cytoskeletal and focal adhesion architecture (scale bars = 50 m). Podocytes treated with dasatinib showed a marked decrease in cell-to-cell contacts, cell size and number of focal adhesions. -tubulin; PubMed: 26517812 Oncotarget Combination of dasatinib and crizotinib impedes the formation of the -tubulin-labeled mitotic spindle. LN-18 cells were treated with dasatinib 0.2 M, crizotinib 4 M or their combination for 48 h. Mitotic spindle were visualized using -tubulin antibody conjugated to a fluorescein-labeled secondary antibody. Nuclei were stained by DAPI. The scale bar denotes 10 m. TNF- PubMed: 17684099 Proc Natl Acad Sci U S A U937 cells were differentiated with vitamin D3, pretreated with the indicated concentrations of drugs for 1 h and stimulated with LPS for 6 h. TNF- secretion was measured by ELISA. The graph shows the mean of two experiments done in duplicate. E-selectin; PubMed: 31110200 Sci Rep HAoECs were treated with DMSO, a dual FAK/Pyk2 inhibitor (PF-271, 2.5 M), a Src inhibitor (Dasatinib, 1 M), or a FAK inhibitor (PF-228, 10 M) for 1 h prior to TNF- (10 ng/ml, 6 h) stimulation. Expression levels of E-selectin was determined using ELISA (n = 3, SEM). VCAM-1; PubMed: 31110200 Sci Rep HAoECs were treated with DMSO, a dual FAK/Pyk2 inhibitor (PF-271, 2.5 M), a Src inhibitor (Dasatinib, 1 M), or a FAK inhibitor (PF-228, 10 M) for 1 h prior to TNF- (10 ng/ml, 6 h) stimulation. Expression levels of VCAM-1 was determined using ELISA (n = 3, SEM). Dasatinib 作用于LMP2A/MYC 双转基因小鼠，可逆转脾肿大。Dasatinib 作用于TgE小鼠 抑制表达LMP2A 的骨髓B 细胞形成的菌落，且使脾脏变小。使用Dasatinib处理Tg6/λ-MYC 小鼠，与对照组相比，脾脏质量明显降低。Dasatinib 作用于LMP2A/MYC 双转基因小鼠，抑制淋巴结肿大。Dasatinib作用于嫁接LMP2A/MYC双转基因小鼠肿瘤细胞的Rag1KO小鼠，可逆转脾肿大。Dasatinib 作用于表达LMP2A的B 淋巴细胞瘤，抑制Lyn磷酸化。[2] 激酶自磷酸化分析: 使用野生型和突变型谷胱甘肽S-转移酶(GST)-Abl融合蛋白 (c-Abl氨基酸220-498位) 进行激酶实验。从谷胱甘肽琼脂糖珠中释放GST-Abl融合蛋白，ATP浓度为5 μM。在用于激酶自磷酸化和体外肽底物磷酸化实验前, 用LAR酪氨酸磷酸酶处理GST-Abl 激酶域融合蛋白。在 30oC下温育1小时后,加入1 mM 钒酸钠，激活LAR磷酸酶。进行免疫印迹分析，比较未处理的GST-Abl激酶和去磷酸化的GST-Abl激酶，使用磷酸化的特点抗体4G10来 确认酪氨酸残基完全去磷酸化(>95%)，使用c-Abl抗体 CST 2862 来确认GST-Abl激酶的平衡负载。实验测定IC50值时所用Dasatinib浓度为0 nM到32 nM。Dasatinib作用于突变型T315I时浓度达到 1,000 nM。在体外肽底物磷酸化实验中使用相同抑制剂浓度。作用于GST-Src激酶和 GST-Lyn激酶的三种抑制剂的浓度范围相同。 Incubation Time: 72小时 Method: Ba/F3 细胞系重复培养三份，然后与浓度逐渐升高的 Dasatinib 温育72小时。通过MTS活性实验测定细胞增殖。IC50值和IC90值取自三组独立实验的平均值。Dasatinib作用的IC50值和IC90值为0 nM 到32 nM 。Dasatinib 作用于突变型T315I时所需浓度达到200 nM。(Only for Reference) Animal Models: EμLMP2A(TgE 和Tg6品种),MYC (λ-MYC), 和LMP2A/λ-MYC双转基因小鼠(Tg6/λ-MYC) Dosages: 30 mg/kg Administration: 腹腔注射(Only for Reference) 从左到右依次将纯溶剂加入产品，现配现用(数据来自Selleck实验检测而非文献)： 4% DMSO+30% PEG 300+5% Tween 80+ddH2O * 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。 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系Selleck为您提供正确的澄清溶液配方） 药物溶于 μL DMSO溶液（母液浓度 mg/mL，注：如该浓度超过该批次药物DMSO溶解度，请先联系Selleck）； 体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL ddH2O，混匀澄清。 体内配方配制方法：取 μL DMSO母液，加入 μL Corn oil，混匀澄清。 注意：1. 首先保证母液是澄清的； 2. 一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。 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 *在配置溶液时，请务必参考Selleck产品标签上、SDS / COA（可在Selleck的产品页面获得）批次特异的分子量使用本工具。 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 ) 在配置溶液时，请务必参考Selleck产品标签上、SDS / 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NCT04155411 Recruiting Drug: Dasatinib Dasatinib|BCR-ABL|Chronic Myeloid Leukemia Shenzhen Second People\'\'s Hospital December 1 2019 Phase 4NCT04115059 Recruiting Drug: Dasatinib Waldenstrom Macroglobulinemia|DASATINIB Jorge J. Castillo MD|Bristol-Myers Squibb|Dana-Farber Cancer Institute November 4 2019 Phase 1NCT03625388 Recruiting Drug: Dasatinib Chronic Myelogenous Leukemia Hikma Pharmaceuticals LLC November 5 2018 Phase 2NCT03193281 Recruiting Drug: Dasatinib|Drug: Imatinib Chronic Myeloid Leukemia University of Auckland New Zealand|Leukaemia & Blood Cancer New Zealand July 17 2017 Phase 2 在订购、运输、储存和使用我们的产品的任何阶段，您遇到的任何问题，均可以通过拨打我们的热线电话400-668-6834，或者技术支持邮箱tech@selleck.cn，直接联系到我们。我们会在24小时内尽快联系您。 操作手册 问题 1： what s the difference between S1021 and S7782? Which one is better for in vivo studies? Usually, hydrate will be more stable and dissolve better than free base. But this compound (S1021) dissolves better in DMSO than hydrate one (S7782). 问题 2： Can I give dasatinib to mice by oral gavage? If so, how to dissolve the drug? Our S1021 Dasatinib in 1% DMSO+30% PEG 300+1% Tween 80 at 30 mg/ml is a suspension which you can administrate to mice via oral gavage. If you want a clear solution, it can be dissolved in 4% DMSO+30% PEG 300+5% Tween 80+ddH2O at 5 mg/ml clearly. The first clinical Src inhibitor (peptidomimetic class) that targets the peptide substrate site of Src, with GI50 of 9-60 nM in cancer cell lines. Dasatinib Monohydrate (BMS-354825)是一种新型有效的多靶点抑制剂，作用于靶点Abl，Src 和 c-Kit，IC50分别为 SU 6656 是一种选择性 Src 家族激酶抑制剂，对Src，Yes，Lyn，和 Fyn 的 IC50 分别为 280 nM，20 nM，130 nM，和 170 nM。 PX-478 2HCl 是一种具有口服活性的选择性hypoxia-inducible factor-1α (HIF-1α)抑制剂。PX-478 2HCl可诱导凋亡并具有抗肿瘤的活性。Phase 1。 Saracatinib (AZD0530)是一种有效的Src抑制剂，无细胞试验中IC50为2.7 nM，对c-Yes， Fyn， Lyn， Blk， Fgr和Lck也具有活性；但对Abl和EGFR (L858R和L861Q)活性较低。Saracatinib可诱导自噬。Phase 2/3。 Features:Saracatinib是第一个作用于人类肿瘤组织Src通路的抑制剂。 Bosutinib (SKI-606) 是一种新型的双重Src/Abl抑制剂，在无细胞试验中IC50分别为1.2 nM 和 1 nM。Bosutinib也可通过阻滞p-ERK、p-S6和p-STAT3的磷酸化来有效地降低PI3K/AKT/mTOR、MAPK/ERK和JAK/STAT3信号通路的活性。Bosutinib可促进自噬。 KX2-391 (Tirbanibulin) 是第一个临床Src抑制剂(拟肽类)，靶向作用于Src的肽底物位点，在癌细胞系中GI50为9-60 nM。Phase 2。 PP1 (AGL 1872, EI 275)是一种有效的Src选择性抑制剂，作用于Lck/Fyn时，IC50为5 nM/6 nM。 PP2 (AG 1879, AGL 1879) 是一种Src家族激酶抑制剂，有效抑制Lck/Fyn，无细胞试验中IC50为4 nM/5 nM，作用于EGFR效果低100倍左右，对ZAP-70，JAK2和PKA没有活性。 WH-4-023 (KIN001-112, KIN112, Dual LCK/SRC inhibitor) 是一种有效的，口服具有活性的Lck/Src抑制剂，无细胞试验中IC50分别为2 nM 和 6 nM。对p38α和KDR的选择性低300倍以上，还能有效抑制SIK（对SIK1、2、3的IC50分别为10、22、60 nM）。 Ibrutinib (PCI-32765)是一种有效的，高选择性的Brutons tyrosine kinase (Btk)抑制剂，无细胞试验中IC50为0.5 nM，对Bmx， CSK， FGR， BRK及HCK适度有效，对EGFR， Yes， ErbB2， JAK3等作用效果较弱。Ibrutinib 可作为Btk配体用于合成包括P13I在内的一系列PROTAC。 Tags: 购买Dasatinib (BMS-354825) | Dasatinib (BMS-354825)供应商 | 采购Dasatinib (BMS-354825) | Dasatinib (BMS-354825)价格 | Dasatinib (BMS-354825)生产 | 订购Dasatinib (BMS-354825) | Dasatinib (BMS-354825)代理商