An inhibitor of Abl and Src
此产品仅用于科学研究,我们不为任何个人用途提供产品和服务
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)
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. |
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. |
参考文献: [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. |
Glycolic acid oxidase inhibitor 1
¥1210.00 ¥1512.00
没有评价数据