Powder: -20°C for 3 years | In solvent: -80°C for 1 year
COTI-2是一种具有口服活性的低毒性抗癌药物,是 p53 突变体激活剂。它通过激活突变型 p53 和抑制PI3K/AKT/mTOR 途径发挥作用,通过 p53 依赖和非依赖机制在 HNSCC 中具有抗肿瘤活性。它诱导多种人肿瘤细胞凋亡,可将突变型 p53 转化为野生型构象。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 269 | 现货 | ||
2 mg | ¥ 378 | 现货 | ||
5 mg | ¥ 622 | 现货 | ||
10 mg | ¥ 987 | 现货 | ||
25 mg | ¥ 1,950 | 现货 | ||
50 mg | ¥ 2,890 | 现货 | ||
100 mg | ¥ 4,330 | 现货 | ||
500 mg | ¥ 9,360 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 683 | 现货 |
产品描述 | COTI-2, an orally available thiosemicarbazone, is an activator of mutant forms of the p53 protein with potential antineoplastic activity. |
体外活性 | COTI-2 (72 h) potently inhibits the proliferation rate of all the tested cell lines. In COLO-205, HCT-15, and SW620 cell lines, COTI-2 markedly inhibits tumor cell proliferation. Relatively low concentrations of COTI-2 are active against all human glioblastoma cell lines tested (U87-MG, SNB-19, SF-268, and SF-295). In SHP-77 cells, COTI-2 treatment with IC50 concentrations causes the induction of early apoptosis among 40 to 47% of total cells. |
体内活性 | In the HT-29 human colorectal tumor xenografts, COTI-2 (10 mg/kg) markedly inhibits tumor growth. Except for reducing tumor volumes at specific times post-treatment, COTI-2 also increases the time required for tumors to reach specified volumes. In the SHP-77 SCLC xenograft model, COTI-2 (3 mg/kg) also markedly inhibits tumor growth. COTI-2 can reduce U87-MG tumor volumes at specific times post-treatment and lengthen the time required for U87-MG xenografts to grow in nude mice. Control tumors in mice treated with vehicle alone take only 5 days to reach an average volume of 828 mm3 while tumors in animals treated with COTI-2 take double that time (10 days) to reach a similar mean volume (857 mm3). Regardless of the route of administration, COTI-2 potently inhibits OVCAR-3 xenograft growth. |
激酶实验 | The interaction of COTI-2 with 227 kinases is tested using the AMBIT BIOSCIENCES KINOMESCAN assay. In brief, streptavidin-coated magnetic beads are treated with biotinylated small molecule ligands for 30 min at 25°C to generate affinity resins for kinase assays. The liganded beads are blocked with excess biotin and washed with blocking buffer (1% BSA, 0.05% Tween 20, 1 mM DTT) to remove unbound ligand and to reduce non-specific binding. Binding reactions are assembled by combining phage lysates, liganded affinity beads, and COTI-2 in 1× binding buffer (20% SeaBlock, 0.17× PBS, 0.05% Tween 20, 6 mM DTT). All reactions are carried out in polystyrene 96-well plates that have been pre-treated with blocking buffer in a final volume of 0.1 mL. |
细胞实验 | COTI-2 is dissolved in 100% dimethyl sulfoxide stock solution and diluted in medium plus FBS such that final DMSO concentrations are 0.5 to 1.0% depending on the experiment.SHP-77 cells are cultured with various concentrations of COTI-2 for 48 h. Cells are then washed twice with 1× cold PBS and stained with Annexin V and 7AAD according to the manufacturer's instructions. Briefly, 5 μL of Annexin V and 7AAD are added to 1×105 cells and incubated for 15 min at room temperature in the dark. Then 400 μL of the 1× binding buffer (100 mM HEPES, pH 7.4, 140 mM NaCl, 2.5 mM CaCl2) is added to the cells. Finally, cells are analyzed using a flow cytometer. |
动物实验 | SHP-77 and HT-29 cells are injected in 50% matrigel into flanks of NCr-nu mice (2×106 cells per injection site) (n=5 mice per group). In the case of SHP-77 xenografts, treatment with COTI-2 begins prior to the appearance of palpable tumors. One day after injection of SHP-77 cells, animals receive 3 mg/kg of COTI-2 (once every two days, up to 38 days). Tumor sizes are estimated at 5, 10, 17, 24, and 38 days, by standard caliper measurements. In the case of HT-29 xenografts, the capacity of COTI-2 to suppress the growth of established tumors is assessed. HT-29 xenografts are allowed to grow to 200 mm3 before starting IP treatment with COTI-2 (10 mg/kg, 5 days a week for 7 weeks) or saline IP. Tumor growth is measured every 4 days by caliper measurement. |
别名 | COTI 2, COTI2 |
分子量 | 366.48 |
分子式 | C19H22N6S |
CAS No. | 1039455-84-9 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 5 mg/mL (13.64 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.7287 mL | 13.6433 mL | 27.2866 mL | 68.2165 mL |
5 mM | 0.5457 mL | 2.7287 mL | 5.4573 mL | 13.6433 mL | |
10 mM | 0.2729 mL | 1.3643 mL | 2.7287 mL | 6.8217 mL |
对于不同动物的给药剂量换算,您也可以参考 更多...
请在以下方框中输入您的动物实验信息后点击计算,可以得到母液配置方法和体内配方的制备方法: 比如您的给药剂量是10 mg/kg,每只动物体重20 g,给药体积100 μL,一共给药动物10 只,您使用的配方为5% DMSO+30% PEG300+5% Tween 80+60% ddH2O。那么您的工作液浓度为2 mg/mL。
母液配置方法:2 mg 药物溶于 50 μL DMSO (母液浓度为 40 mg/mL), 如您需要配置的浓度超过该产品的溶解度,请先与我们联系。
体内配方的制备方法:取 50 μL DMSO 主液,加入 300 μL PEG300, 混匀澄清,再加 50 μL Tween 80,混匀澄清,再加 600 μL ddH2O, 混匀澄清。
您可能有的问题的答案可以在抑制剂处理说明中找到,包括如何准备库存溶液,如何存储产品,以及基于细胞的分析和动物实验需要特别注意的问题。
COTI-2 1039455-84-9 Apoptosis p53 COTI 2 inhibit Inhibitor HNSCC COTI2 low anti-cancer anti-proliferative toxicity TNBC MDM-2/p53 orally inhibitor