Powder: -20°C for 3 years | In solvent: -80°C for 1 year
MKC3946 是一种有效的可溶性 IRE1α 抑制剂,可在多发性骨髓瘤细胞系中引发适度的生长抑制,可用于癌症研究。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 558 | 现货 | ||
5 mg | ¥ 1,650 | 现货 | ||
10 mg | ¥ 2,710 | 现货 | ||
25 mg | ¥ 4,530 | 现货 | ||
50 mg | ¥ 6,460 | 现货 | ||
100 mg | ¥ 8,830 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 1,520 | 现货 |
产品描述 | MKC3946 is an effective and soluble IRE1α inhibitor which triggered modest growth inhibition in multiple myeloma cell lines. |
体外活性 | MKC-3946通过阻断XBP1 mRNA剪接,并对AML细胞展现细胞毒性。MKC-3946抑制由tunicamycin (TM)在NB4细胞(B)及患者AML样本[1]中诱导的XBP1S表达。MKC-3946阻止因突变前胰岛素产生造成的内质网应激响应中XBP1 mRNA的剪接[2]。作为IRE1α核糖核酸酶领域抑制剂,MKC-3946阻断XBP1 mRNA剪接,在多发性骨髓瘤(MM)细胞中触发适度的生长抑制。MKC-3946以剂量依赖方式抑制由Tm诱导的XBP1s表达,但不影响IRE1α的磷酸化。MKC-3946阻断XBP1剪接,并增强由bortezomib或17-AAG诱导的细胞毒性。MKC-3946(10μM)增强了由bortezomib或17-AAG引起的内质网应激介导的凋亡,并即使在BMSCs或外源性IL-6存在的情况下,也增强了内质网应激剂的细胞毒性[3]。 |
体内活性 | MKC-3946(100 mg/kg,i.p.)在体内ER应激模型中抑制XBP1剪接,与显著的MM细胞生长抑制相关,无论是单独使用还是与博腾珠单抗联用。MKC-3946显著降低了治疗组相比对照组的MM肿瘤生长。通过MKC-3946抑制XBP1剪接与体内MM生长减少相关,无论是单独使用还是与博腾珠单抗联用[3]。 |
细胞实验 | For each assay, the various numbers of cells (1,000 for cell proliferation and 10,000 for cell viability assays) are seeded in 96-well plates, followed by either vehicle (DMSO) or increasing concentrations of the drug. For detection of relative numbers of living cells, 10 μL of MTT (5 mg/mL) is added to each well, placed in an incubator for four hours, followed by centrifugation (1,000 rpm, 5 min); 100 μL of supernatant media from each well are carefully removed and 100 μL of SDS buffer (20% in water) is added to dissolve the crystals. Results are further read on the spectrophotometer machine at 570 nM wavelength. Half maximal inhibitory concentration (IC50) is calculated using the GraphPad Prism 5. A synergy of combination of two drugs is determined using the CalcuSyn software. The extent of drug interaction between the two drugs is determined using the combination index (CI) for mutually exclusive drugs. Different CI values are obtained when solving the equation for different concentrations of drugs. A CI of 1 indicates an additive effect, whereas a CI of <1denotes synergy. All experiments are repeated at least three times [1]. |
动物实验 | CB17 SCID mice (48-54 days old) are injected subcutaneously with 1×10^7 RPMI 8226 cells mixed with Matrigel on day 0, and receive treatment for 21 days starting on day1. Mice are assigned into 4 groups (n=8): daily intraperitoneal injections of 100 mg/kg MKC-3946; intravenous injections of 0.15 mg/kg bortezomib twice a week; a combination of MKC-3946 intraperitoneally with bortezomib intravenously; and 10% HPBCD intraperitoneally with normal saline intravenously as vehicle control. Tumor volume is calculated from caliper measurements every 3 to 4 days; mice are killed when tumors reached 1.5 cm in length. Survival is evaluated from the first day of treatment until death [3]. |
分子量 | 380.46 |
分子式 | C21H20N2O3S |
CAS No. | 1093119-54-0 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 30 mg/mL (78.85 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 2.6284 mL | 13.142 mL | 26.284 mL | 65.7099 mL |
5 mM | 0.5257 mL | 2.6284 mL | 5.2568 mL | 13.142 mL | |
10 mM | 0.2628 mL | 1.3142 mL | 2.6284 mL | 6.571 mL | |
20 mM | 0.1314 mL | 0.6571 mL | 1.3142 mL | 3.2855 mL | |
50 mM | 0.0526 mL | 0.2628 mL | 0.5257 mL | 1.3142 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。
MKC3946 1093119-54-0 Cell Cycle/Checkpoint IRE1 Inositol requiring enzyme 1 inhibit Inhibitor MKC-3946 MKC 3946 inhibitor