| 名称 | Dasatinib |
| 描述 | Dasatinib (BMS-354825) is a tyrosine kinase inhibitor that inhibits Src and Bcr-Abl (Ki=16/30 pM) and is orally active and ATP-competitive. Dasatinib has antitumor activity and is used in the treatment of leukemia and lymphoma. |
| 细胞实验 | Ba/F3 cell lines were plated in triplicate and incubated with escalating concentrations of imatinib, AMN107, or BMS-354825 for 72 hours. Proliferation was measured using a methanethiosulfonate-based viability assay. IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90 determinations were 0 to 2,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The imatinib concentration range was extended to 6,400 nmol/L for mutants with IC50 >2,000 nmol/L. The BMS-354825 concentration range was extended to 200 nmol/L for mutant T315I [1]. |
| 激酶实验 | Kinase assays using wild-type and mutant glutathione S-transferase (GST)–Abl fusion proteins (c-Abl amino acids 220-498) were done as described, with minor alterations. GST-Abl fusion proteins were released from glutathione-Sepharose beads before use; the concentration of ATP was 5 μmol/L. Immediately before use in kinase autophosphorylation and in vitro peptide substrate phosphorylation assays, GST-Abl kinase domain fusion proteins were treated with LAR tyrosine phosphatase according to the manufacturer's instructions. After 1-hour incubation at 30°C, LAR phosphatase was inactivated by addition of sodium vanadate (1 mmol/L). Immunoblot analysis comparing untreated GST-Abl kinase to dephosphorylated GST-Abl kinase was routinely done using phosphotyrosine-specific antibody 4G10 to confirm complete (>95%) dephosphorylation of tyrosine residues and c-Abl antibody CST 2862 to confirm equal loading of GST-Abl kinase. The inhibitor concentration ranges for IC50 determinations were 0 to 5,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The BMS-354825 concentration range was extended to 1,000 nmol/L for mutant T315I. These same inhibitor concentrations were used for the in vitro peptide substrate phosphorylation assays. The three inhibitors were tested over these same concentration ranges against GST-Src kinase and GST-Lyn kinase [1]. |
| 动物实验 | For in vivo studies, dasatinib (50 mg/kg) was prepared for daily oral gavage (5 d/wk) in 80 mmol/L sodium citrate buffer, pH 3.0. For the orthotopic murine model, mice were randomized on day 10 based on bioluminescence activity to receive drug or vehicle. In the metastatic murine model, mice received dasatinib or vehicle, as described earlier, starting 2 days before intracardiac injection (pretreatment), or on day 11 following randomization (posttreatment) [4]. |
| 体外活性 | 方法：8 种甲状腺癌细胞用 Dasatinib (0.019-1.25 μmol/L) 处理 3 天，使用 SRB 方法检测细胞增殖。
结果：Dasatinib 对 C643、TPC1、BCPAP、SW1736、K1、8505C、HTh74、HTh7 细胞的 IC50 分别为 0.09、0.03、0.04、0.08、0.4、2.7、>5、1.6 μmol/L。[1]
方法：人肺癌细胞 NCI-H1975 和 NCI-H1650 用 Dasatinib (2.5-20 μM) 处理 48 h，使用 Flow Cytometry 检测细胞凋亡情况。
结果：Dasatinib 在 10 和 20 μM 下诱导 NCI-H1975 和 NCI-H1650 细胞凋亡。[2] |
| 体内活性 | 方法：为检测体内抗肿瘤活性，将 Dasatinib (50 mg/kg in 80 mmol/L sodium citrate buffer, pH 3.0) 口服给药给携带人甲状腺癌肿瘤 BCPAP 或 8505C 的 athymic nude 小鼠，每周五天，持续二十天。
结果：Dasatinib 显著抑制 BCPAP 原位肿瘤，最终肿瘤体积抑制了 90% 以上。Dasatinib 治疗在任何时间点都没有显著抑制 8505C 来源的肿瘤的生长。[1]
方法：为研究对神经炎症的影响，将 Dasatinib (20 mg/kg in 4%DMSO+30%PEG+5%Tween 80) 腹腔注射或口服给药给 C57BL6/N 小鼠，每天一次给药四天，随后腹腔注射 LPS (10 mg/kg) 诱导体内神经炎症反应。
结果：腹腔注射和口服 Dasatinib 抑制 LPS 诱导的野生型小鼠脑中小胶质细胞/星形胶质细胞活化、促炎细胞因子水平和中性粒细胞滚动。[3] |
| 存储条件 | store at low temperature,keep away from moisture | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 9.1 mg/mL (18.65 mM), Suspension.
DMSO : 262.5 mg/mL (537.9 mM), Sonication is recommended.
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| 关键字 | WiDr | Src | prostate | PC3 | orally | K562 | Inhibitor | inhibit | Dasatinib | colon | CML | c-Kit (wt) | c-Kit (D816V) | cKit | breast | BMS354825 | BMS 354825 | Bcr-Abl | BcrAbl | Autophagy | Apoptosis | antitumor | antiproliferative | active | Abl |
| 相关产品 | Urea | Naringin | Guanidine hydrochloride | Aceglutamide | Alginic acid | Cysteamine hydrochloride | Metronidazole | Hemin | Hydroxychloroquine | Stavudine | Tamoxifen | Paeonol |
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