Dasatinib (BMS-354825)

目录号:S1021 中文名称:达沙替尼

仅限科研使用

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。

Dasatinib (BMS-354825) Chemical Structure

CAS: 302962-49-8

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 6691.23 现货
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客户使用Selleck生产的Dasatinib (BMS-354825)发表文献469篇:

产品安全说明书

Src抑制剂选择性比较

相关Src产品

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 M4\qVWdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NXvxXWh3PzJiaB?= MVTEUXNQ M4\4VWlEPTB;MD6wNFAxPyEQvF2= NF\COHc9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9zN{m1OlA5OCd-MUe5OVYxQDB:L3G+
K562 NUGxbHdDT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Mk\IO|IhcA>? M{TZbWROW09? NEn1NWFKSzVyPUCuNFAyKM7:TR?= M4m1blxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF5OUW2NFgxLz5zN{m1OlA5ODxxYU6=
M07e NHHHe5lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MUO3NkBp MnXzSG1UVw>? M4PEOWlEPTB;MD6wNFEzKM7:TR?= NVzwdJFxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUe5OVYxQDBpPkG3PVU3ODhyPD;hQi=>
ALL3 NInzepNEgXSxdH;4bYMhSXO|YYm= NYTvPYx[OC5zzszN M4\jTVczKGh? M1zpVWROW09? NIrSTlNKSzVyPUCuNFAxPCEQvF2= NXPpO3ZQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUm4PFk2PDBpPkG5PFg6PTRyPD;hQi=>
CML MUHHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M3LG[VIxKG2rbh?= NGrOXXhFVVOR M4iwfmlEPTB;MD6wNFEh|ryP NUO3dHRCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMUmyNVkxOTZpPkG5NlE6ODF4PD;hQi=>
BA/F3 MWnHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M363N|czKGh? NGnQSZBFVVOR M2jlbmlEPTB;Nj61PFkh|ryP MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzB6OE[0OEc,OjNyOEi2OFQ9N2F-
BA/F3 MmHlS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MoTaO|IhcA>? M3\PdWROW09? M4fSPWlv\HWlZYOgZY51cXC{b3zp[oVz[XSrdnWgZYN1cX[rdImgZYdicW6|dDDtc5V{\SCEQT;GN{Bk\WyuczDlfJBz\XO|aX7nJGJkei2DYnygUVM2OVRibYX0ZY51KHerdHigTWM2OCCxZjCwMlAxODh|zszN NWXUN|lxRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwPFg3PDRpPkKzNFg5PjR2PD;hQi=>
BA/F3 NGLMWWNIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NEnwOoU4OiCq MkX4SG1UVw>? NYrifpBvUW6mdXPld{BidnSrcILvcIln\XKjdHn2[UBi[3Srdnn0fUBi\2GrboP0JI1wfXOnIFLBM2Y{KGOnbHzzJIV5eHKnc4Ppcochf2muZDD0fZBmKEKlcj3BZowhf2m2aDDJR|UxKG:oIECuNFA1Pc7:TR?= NV3CPWlZRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOwPFg3PDRpPkKzNFg5PjR2PD;hQi=>
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BA/F3 NYKzZVFvT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NIHneZY4OiCq MW\EUXNQ MmDsTY5lfWOnczDjfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKEKFUj3BRmwhTTJ3NVugcZV1[W62IHHzd4V{e2WmIHHzJIdzd3e2aDDJcohq[mm2aX;uJJdqfGhiSVO1NEBw\iByLkCwN|LPxE1? NW\QboI{RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkOzNFE4ODNpPkKzN|AyPzB|PD;hQi=>
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BA/F3 NWDFXohNT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= M3rWV|czKGh? MorOSG1UVw>? M4fYemlv\HWlZYOgZ5l1d3SxeHnjbZR6KGGpYXnud5QhdW:3c3WgRmEwTjNiY3XscJMh\XiycnXzd4lv\yCEQ2KtRWJNKEV|NUnWJI12fGGwdDDhd5Nme3OnZDDhd{Boem:5dHigTY5pcWKrdHnvckB4cXSqIFnDOVAhd2ZiMD6wNFE{|ryP MX28ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzNyMUewN{c,OjN|MEG3NFM9N2F-
BA/F3 MlzqS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? NETpTlQ4OiCq MUHEUXNQ MWDJcoR2[2W|IHP5eI91d3irY3n0fUBi\2GrboP0JI1wfXOnIFLBM2Y{KGOnbHzzJIV5eHKnc4Ppcochf2muZDD0fZBmKEKFUj3BRmwh[XO|ZYPz[YQh[XNiZ4Lve5RpKEmwaHnibZRqd25id3n0bEBKSzVyIH;mJFAvODBzOd88US=> MmftQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN|MEG3NFMoRjJ|M{CxO|A{RC:jPh?=
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BA/F3 Mn;uS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mmj1O|IhcA>? NULzZ4RnTE2VTx?= Mm\qTY5lfWOnczDjfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{BmgHC{ZYPzbY5oKEKFUj3BRmwhXDNzNVmgcZV1[W62IHHzd4V{e2WmIHHzJIdzd3e2aDDJcohq[mm2aX;uJJdqfGhiSVO1NEBw\iB|LkdOwG0> Mn\6QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN|MEG3NFMoRjJ|M{CxO|A{RC:jPh?=
BA/F3 NVH3PYNGT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWTKWIFIPzJiaB?= MmroSG1UVw>? MonuTY5lfWOnczDjfZRwfG:6aXPpeJkh[WejaX7zeEBud3W|ZTDCRU9HOyClZXzsd{Bie3Onc4Pl[EBieyCpcn;3eIghUW6qaXLpeIlwdiC5aYToJGlEPTBib3[gNk42|ryP NGfnd5Y9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{M{OwNVcxOyd-MkOzNFE4ODN:L3G+
T cell MmrOS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? Mlm3O|IhcA>? NXvwWpI4TE2VTx?= NFzWWZJKdmirYnn0d{BidnSrIFPEN{0h[W6mIHHueIkhS0R{OD3pcoR2[2WmIGSgZ4VtdCCycn;sbYZmemG2aX;uJJdqfGhiSVO1NEBw\iByLkCwN:69VQ>? MnHDQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOTdzNUS1NVIoRjF5MUW0OVEzRC:jPh?=
WiDr MWXHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? M4PhU|czKGh? NVT6WnFUTE2VTx?= MljRTWM2OD1yLkC1NkDPxE1? M4jGTlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3NkG1OVEzLz5zNU[xOVUyOjxxYU6=
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MDA-MB-231 M3XIdGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NEftSXk4OiCq NHnSS5NFVVOR NULU[3JkUUN3ME2wMlAyOiEQvF2= M3TTZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzF3NkG1OVEzLz5zNU[xOVUyOjxxYU6=
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MALME-3M MVrDfZRwfG:6aXOgRZN{[Xl? MYm3NkBp MYXEUXNQ MlvFS2k2OD14Lk[xJO69VQ>? Ml7sQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjRyMUWzNlcoRjJ2MEG1N|I4RC:jPh?=
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RXF 393NL MUHDfZRwfG:6aXOgRZN{[Xl? M4fnOVQh\GG7cx?= NXn2NmdETE2VTx?= M33rVWlEPTB;MD6wNlE4KM7:TR?= M3PaZlxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ|MkWzNFc1Lz5{M{K1N|A4PDxxYU6=
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Assay
Methods Test Index PMID
Western blot phospho-c-Abl(Tyr245) / phospho-c-Src(Tyr416) p27 / p21 p-FAK / p-STAT3 cleaved caspase 3 23049975 20145167 23721490
Growth inhibition assay IC50 23721490
Immunofluorescence SRC / Met F-actin / Actinin-4 / Paxillin α-tubulin 26517812 31053734
ELISA TNF-α E-selectin VCAM-1 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]
  • 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]
  • 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。
动物实验:[2]
  • 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

溶解度(25°C)

体外

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 3年 -20°C 粉状
2年 -80°C 溶于溶剂

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)

mg/kg g μL

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
%DMSO %

计算结果:

工作液浓度: mg/ml;

DMSO母液配制方法: mg 药物溶于μL DMSO溶液(母液浓度mg/mL,: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: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: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。

摩尔浓度计算器

质量 浓度 体积 分子量

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05198843 Recruiting Drug: Dasatinib|Dietary Supplement: Icosapent Ethyl Anatomic Stage IV Breast Cancer AJCC v8|Metastatic Triple-Negative Breast Inflammatory Carcinoma National Cancer Institute (NCI) March 25 2022 Phase 1|Phase 2
NCT04925648 Recruiting Drug: Dasatinib|Drug: Darolutamide Metastatic Prostate Cancer St Vincent''s Hospital Sydney October 18 2021 Phase 2
NCT04933526 Recruiting Drug: Flumatinib|Drug: Dasatinib Chronic Myeloid Leukemia in Chronic Phase Shenzhen Second People''s Hospital July 1 2021 Phase 4
NCT05433896 Completed Drug: Dasatinib ASD|Drug: Omeprazole 40 MG Pharmacokinetics|Drug Interactions Xspray Pharma AB|Axis Clinicals Limited November 1 2020 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

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常见问题及建议解决方法

问题 1:
what’s the difference between S1021 and S7782? Which one is better for in vivo studies?

回答:
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?

回答:
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.