Dasatinib (BMS-354825)

For research use only. Not for use in humans.

目录号:S1021 中文名称:达沙替尼

Dasatinib (BMS-354825) 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 (BMS-354825)发表文献412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
M07ep210 MkXES5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NGTRcZM4OiCq MnG2SG1UVw>? M3TOSWlEPTB;MD6wNFAxPyEQvF2= M3i0c|xiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5OUW2NFgxLz5zN{m1OlA5ODxxYU6=
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M07e NFq5[4tIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NH;Sb4o4OiCq MmHjSG1UVw>? M17RcWlEPTB;MD6wNFEzKM7:TR?= NHXWfGk9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{m1OlA5OCd-MUe5OVYxQDB:L3G+
ALL3 NFjqZVhEgXSxdH;4bYMhSXO|YYm= NYPLcGJGOC5zzszN M1XSNlczKGh? M{Xr[GROW09? M3HsV2lEPTB;MD6wNFA1KM7:TR?= NX7He2NmRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm4PFk2PDBpPkG5PFg6PTRyPD;hQi=>
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BA/F3 M1zVemdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 MWG3NkBp NIXPdpBFVVOR M2rMR2lv\HWlZYOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCEQ2KtRWJNKEV{NUXLJI12fGGwdDDhd5Nme3OnZDDhd{Boem:5dHigTY5pcWKrdHnvckB4cXSqIFnDOVAhd2ZiMD6wNFMz|ryP NXPWXZU1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOzNFE4ODNpPkKzN|AyPzB|PD;hQi=>
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BA/F3 NXflXVkzT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MmjjO|IhcA>? M{fNWmROW09? MWDJcoR2[2W|IHP5eI91d3irY3n0fUBi\2GrboP0JI1wfXOnIFLBM2Y{KGOnbHzzJIV5eHKnc4PpcochSkOULVHCUEBGOzV7VjDteZRidnRiYYPz[ZN{\WRiYYOg[5Jwf3SqIFnubIljcXSrb36ge4l1cCCLQ{WwJI9nKDBwMECxN:69VQ>? MXq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzNyMUewN{c,OjN|MEG3NFM9N2F-
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T cell NEXt[HJIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYq3NkBp Mlm5SG1UVw>? MUjJcohq[mm2czDhcpRqKEOGMz2gZY5lKGGwdHmgR2QzQC2rbnT1Z4VlKFRiY3XscEBxem:uaX\ldoF1cW:wIIfpeIghUUN3MDDv[kAxNjByM988US=> NUPybWxyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUexOVQ2OTJpPkG3NVU1PTF{PD;hQi=>
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MDA-MB-231 NYfWXWlRT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M2q0[VczKGh? MlHJSG1UVw>? M1TwbWlEPTB;MD6wNVIh|ryP MXm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8yPTZzNUWxNkc,OTV4MUW1NVI9N2F-
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
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.

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.

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.

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.

23721490 20145167 23049975
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
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.

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.

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.

31053734 26517812
ELISA