Dasatinib

For research use only. Not for use in humans.

目录号:S1021 别名: BMS-354825 中文名称:达沙替尼

Dasatinib Chemical Structure

CAS No. 302962-49-8

Dasatinib (BMS-354825) 是一种新型有效的多靶点抑制剂,作用于AblSrcc-Kit,在无细胞试验中IC50分别为 <1 nM、0.8 nM 和 79 nM。Dasatinib 可诱导自噬和凋亡并具有抗肿瘤的活性。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1142.64 现货
RMB 1224.97 现货
RMB 3039.93 现货
RMB 5487.3 现货
RMB 6691.23 现货
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客户使用Selleck生产的Dasatinib发表文献386篇:

产品安全说明书

Src抑制剂选择性比较

生物活性

产品描述 Dasatinib (BMS-354825) 是一种新型有效的多靶点抑制剂,作用于AblSrcc-Kit,在无细胞试验中IC50分别为 <1 nM、0.8 nM 和 79 nM。Dasatinib 可诱导自噬和凋亡并具有抗肿瘤的活性。
靶点
Abl [1]
(Cell-free assay)
Src [1]
(Cell-free assay)
c-Kit (D816V) [2]
(Cell-free assay)
c-Kit (wt) [2]
(Cell-free assay)
0.6 nM 0.8 nM 37 nM 79 nM
体外研究

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]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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NCI-H1304 M1;Vemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NYr2c41CUUN3ME2yPE4yPjJ6IN88US=> NEnhPIc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPDJzLze+V2FPT0WUPD;hQi=>
BC-1 Mn3SS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MYDJR|UxRTJ6Lk[1NUDPxE1? MYm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOFIyNyd-U1HOS2VTRC:jPh?=
NCI-H64 NWfaR2xQT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NI\nOXVKSzVyPUK5MlYzPTNizszN MkDHQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVQzOS9pPmPBUmdGWjxxYU6=
MOLT-16 M4HNXWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NIf6R5FKSzVyPUK5MlYzQTJizszN NGfwdJI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPDJzLze+V2FPT0WUPD;hQi=>
U-87-MG M2\ETGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvNeVBRUUN3ME2zNE44PjZizszN M2r3UlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE1OjFxJ{7TRW5ITVJ:L3G+
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EB-3 MVvHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M2jONmlEPTB;M{SuN|EyPyEQvF2= MkLoQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVQzOS9pPmPBUmdGWjxxYU6=
HCC1187 M13TNGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXW2fWVpUUN3ME2zOU45ODV{IN88US=> NHnFS5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPDJzLze+V2FPT0WUPD;hQi=>
SK-PN-DW MWTHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MX;JR|UxRTN4LkG5OFMh|ryP NUexVZYzRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>
JVM-3 MmTaS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NI\hV21KSzVyPUO3MlI{OzhizszN MmHKQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVQzOS9pPmPBUmdGWjxxYU6=
HCC2157 NGG2cHhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVv0No5kUUN3ME2zO{46QTR4IN88US=> MVe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOFIyNyd-U1HOS2VTRC:jPh?=
A4-Fuk NX;3VVlsT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NYS0OZlGUUN3ME2zPE4yODB7IN88US=> NF\JWoM9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPDJzLze+V2FPT0WUPD;hQi=>
COR-L279 MV7Hdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NYCwVoV2UUN3ME20NE4zQDVzIN88US=> M1GyRVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE1OjFxJ{7TRW5ITVJ:L3G+
DEL NIjuNlhIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MWTJR|UxRTRzLkmwPFYh|ryP MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOFIyNyd-U1HOS2VTRC:jPh?=
NCI-H1395 M3r1Xmdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWPJR|UxRTR{LkCxOlMh|ryP NGrhVZI9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPDJzLze+V2FPT0WUPD;hQi=>
MHH-NB-11 NXLkSnJbT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MVnJR|UxRTR|LkC4NVgh|ryP MlXtQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVQzOS9pPmPBUmdGWjxxYU6=
NCI-H2107 M4[yU2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWHJR|UxRTR|LkS4OFYh|ryP M2PGb|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE1OjFxJ{7TRW5ITVJ:L3G+
NEC8 MkPmS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M3W3S2lEPTB;NESuN|M3KM7:TR?= NHLwSWg9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;3e5cv\WKrLnHjMpVsN2OqZX3icE9kd22yb4Xu[H9z\XCxcoTfZ4Fz\C:FSFXNRmwyPDJzLze+V2FPT0WUPD;hQi=>
COLO-684 MXPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MWXJR|UxRTR4LkKyOVgh|ryP MUi8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOFIyNyd-U1HOS2VTRC:jPh?=
LS-411N MnrtS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NEfXcmRKSzVyPUS4MlQ4PDhizszN NX3rVo9GRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>

... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
phospho-c-Abl(Tyr245) / phospho-c-Src(Tyr416); 

PubMed: 23049975     


Protein levels of phosphorylated c-Abl (Tyr245), c-Abl, phosphorylated c-Src (Tyr416), c-Src, and GAPDH in NSC-34 cells overexpressing human wild-type or mutant SOD1s treated with various concentrations of dasatinib were measured by western blot. Cells were cultured in serum-free culture medium with doxycycline (Dox, 2 µg/ml), and western blot was performed at 24 h after dasatinib addition.

p27 / p21; 

PubMed: 20145167     


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     


The effect of dasatinib in cell signalling. Western blot analysis with phosphorylated Src, FAK, Stat3, Akt and MAPK in HCC cell lines after 24 hours treatment of dasatinib. The cell lines were arranged according to their IC50 to dasatinib. The top three were most sensitive, the bottom 3 were least sensitive.

cleaved caspase 3; 

PubMed: 20145167     


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.

23049975 20145167 23721490
Growth inhibition assay
IC50; 

PubMed: 23721490     


9 HCC cell lines were exposed to the dedicated concentrations of dasatinib for 72 hours, and IC50 was tested by MTS. Results represent the mean (± SD) of three experiments.

23721490
Immunofluorescence
SRC / Met; 

PubMed: 26517812     


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 μm. 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     


Conditionally immortalized differentiated podocytes treated for one-hour with 2 µM kinase inhibitor were stained for F-actin (phalloidin), α-actinin-4, paxillin, and nuclei (Hoechst 33342) to assess cytoskeletal and focal adhesion architecture (scale bars = 50 µm). Podocytes treated with dasatinib showed a marked decrease in cell-to-cell contacts, cell size and number of focal adhesions.

α-tubulin; 

PubMed: 26517812     


Combination of dasatinib and crizotinib impedes the formation of the α-tubulin-labeled mitotic spindle. LN-18 cells were treated with dasatinib 0.2 μM, crizotinib 4 μM or their combination for 48 h. Mitotic spindle were visualized using α-tubulin antibody conjugated to a fluorescein-labeled secondary antibody. Nuclei were stained by DAPI. The scale bar denotes 10 μm.

26517812 31053734
ELISA
TNF-α; 

PubMed: 17684099     


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-α secretion was measured by ELISA. The graph shows the mean of two experiments done in duplicate.

E-selectin; 

PubMed: 31110200     


HAoECs were treated with DMSO, a dual FAK/Pyk2 inhibitor (PF-271, 2.5 μM), a Src inhibitor (Dasatinib, 1 μM), or a FAK inhibitor (PF-228, 10 μM) for 1 h prior to TNF-α (10 ng/ml, 6 h) stimulation. Expression levels of E-selectin was determined using ELISA (n = 3, ±SEM).

VCAM-1; 

PubMed: 31110200     


HAoECs were treated with DMSO, a dual FAK/Pyk2 inhibitor (PF-271, 2.5 μM), a Src inhibitor (Dasatinib, 1 μM), or a FAK inhibitor (PF-228, 10 μM) for 1 h prior to TNF-α (10 ng/ml, 6 h) stimulation. Expression levels of VCAM-1 was determined using ELISA (n = 3, ±SEM).

17684099 31110200
体内研究 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]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

激酶实验:[1]
- 合并

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。
细胞实验: [1]
- 合并
  • Cell lines: Ba/F3细胞系
  • Concentrations: 0 nM-32 nM
  • 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)
动物实验:[2]
- 合并
  • 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)

溶解度 (25°C)

体外 DMSO 98 mg/mL (200.81 mM)
Water Insoluble
Ethanol Insoluble
体内 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
5mg/mL

* 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。

化学数据

分子量 488.01
化学式

C22H26ClN7O2S

CAS号 302962-49-8
储存条件 粉状
溶于溶剂
别名 BMS-354825

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
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)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

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

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

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 )

  • C1
    V1
    C2
    V2