Dasatinib hydrochloride
(Synonyms: 达沙替尼盐酸盐; BMS-354825 hydrochloride) 目录号 : GC35812
An inhibitor of Abl and Src
Cas No.:854001-07-3
Sample solution is provided at 25 µL, 10mM.
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Dasatinib is a potent inhibitor of the non-
1.Lombardo, L.J., Lee, F.Y., Chen, P., et al.Discovery of N-(2-chloro-6-methyl-phenyl)-2-(6-(4-(2-hydroxyethyl)-piperazin-1-yl)-2-methylpyrimidin-4-ylamino)thiazole-5-carboxamide (BMS-354825),a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assaysJ. Med. Chem.47(27)6658-6661(2004) 2.Das, J., Chen, P., Norris, D., et al.2-aminothiazole as a novel kinase inhibitor template. Structure-activity relationship studies toward the discovery of N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)-1-piperazinyl)]-2-methyl-4-pyrimidinyl]amino)]-1,3-thiazole-5-carboxamide (Dasatinib, BMS-354825) as a potent pan-Src kinase inhibitorJ. Med. Chem.49(23)6819-6823(2006) 3.Davis, M.I., Hunt, J.P., Herrgard, S., et al.Comprehensive analysis of kinase inhibitor selectivityNat. Biotechnol.29(11)1046-1051(2011) 4.Carter, T.A., Wodicka, L.M., Shah, N.P., et al.Inhibition of drug-resistant mutants of ABL, KIT, and EGF receptor kinasesProc. Natl. Acad. Sci. USA102(31)11011-11016(2005) 5.El-Amm, J., Freeman, A., Patel, N., et al.Bone-targeted therapies in metastatic castration-resistant prostate cancer: Evolving paradigmsProstate Cancer20131-10(2013) 6.Distler, J.H.W., and Distler, O.Intracellular tyrosine kinases as novel targets for anti-fibrotic therapy in systemic sclerosisRheumatology47(Suppl 5)10-11(2008) 7.McFarland, K.L., and Wetzstein, G.A.Chronic myeloid leukemia therapy: Focus on second-generation tyrosine kinase inhibitorsCancer Control16(2)132-140(2009)
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Cell experiment: |
Ba/F3 cell lines are plated in triplicate and incubated with escalating concentrations of STI571, AMN107, or Dasatinib for 72 hours. Proliferation is measured using a methanethiosulfonate-based viability assay (CellTiter96 Aqueous One Solution Reagent). IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90determinations are 0 to 2,000 nM (STI571 and AMN107) or 0 to 32 nM (Dasatinib). The STI571 concentration range is extended to 6,400 nM for mutants with IC50>2,000 nM. The Dasatinib concentration range is extended to 200 nM for mutant T315I. |
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Animal experiment: |
Mice[3]Male athymic nude mice (25 grams; 5-week old) are used. Dasatinib (50 mg/kg) is prepared for daily oral gavage (5 d/wk) in 80 mM sodium citrate buffer, pH 3.0. For the orthotopic murine model, mice are randomized on day 10 based on bioluminescence activity to receive drug or vehicle. In the metastatic murine model, mice receives dasatinib or vehicle, as described earlier, starting 2 days before intracardiac injection (pretreatment), or on day 11 following randomization (posttreatment).Rats[4]Dasatinib is dosed to male Wistar-Han (WH) rats at 50 mg/kg orally in 0.5% methylcellulose. The automated rat blood collection device is programmed to collect 200 μL of blood at predetermined intervals. At each time point, the accusampler is programmed to directly spot 20 μL of blood twice (two spots) onto the DBS card. The remaining 160 μL of liquid blood is collected into sodium EDTA-containing tubes. Plasma samples are obtained after immediate centrifugation of blood at 11,000 rpm for 5 min. The plasma samples are stored at −80°C until analyses. The DBS samples are dried under room temperature for a minimum of 2 h and stored in a plastic bag in the dessicator until sample analysis. |
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References: [1]. O'Hare T, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant STI571-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. |
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| Cas No. | 854001-07-3 | SDF | |
| 别名 | 达沙替尼盐酸盐; BMS-354825 hydrochloride | ||
| Canonical SMILES | O=C(C1=CN=C(S1)NC2=NC(C)=NC(N3CCN(CC3)CCO)=C2)NC4=C(C=CC=C4Cl)C.[H]Cl | ||
| 分子式 | C22H27Cl2N7O2S | 分子量 | 524.47 |
| 溶解度 | DMSO: 15 mg/mL (28.60 mM and warming); Water: 10 mg/mL (19.07 mM) | 储存条件 | Store at 2-8°C,stored under nitrogen |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9067 mL | 9.5334 mL | 19.0669 mL |
| 5 mM | 0.3813 mL | 1.9067 mL | 3.8134 mL |
| 10 mM | 0.1907 mL | 0.9533 mL | 1.9067 mL |
| 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 | 只 |
| 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GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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，
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 saline，混匀澄清。
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。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet