Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Agerafenib (CEP32496) 是口服高效的 BRAFV600E 抑制剂,Kd 为 14 nM。
规格 | 价格/CNY | 货期 | 数量 | |
---|---|---|---|---|
1 mg | ¥ 497 | 现货 | ||
2 mg | ¥ 737 | 现货 | ||
5 mg | ¥ 1,180 | 现货 | ||
10 mg | ¥ 1,980 | 现货 | ||
25 mg | ¥ 3,780 | 现货 | ||
50 mg | ¥ 5,450 | 现货 | ||
100 mg | ¥ 7,650 | 现货 | ||
500 mg | ¥ 15,300 | 现货 | ||
1 mL * 10 mM (in DMSO) | ¥ 1,360 | 现货 |
产品描述 | Agerafenib (CEP32496) is a highly potent inhibitor of BRAF. |
靶点活性 | c-Kit:2 nM(Kd), PDGFRβ:2 nM(Kd), Abl-1:3 nM(Kd), Lck:2 nM(Kd), RET:2 nM(Kd) |
体外活性 | 在Colo-205异种移植小鼠模型中CEP-32496(30 mg/kg,口服,BID)显示肿瘤停滞和部分肿瘤消退(PR)的发生率为40%,而100 mg/kg剂量组显示肿瘤停滞和PR的发生率为80%.每天两次口服30 mg/kg CEP-32496处理肿瘤裂解物,在给药后2小时和6小时,分别抑制50%和75%归一化的pMEK,而给携带Colo-205移植瘤的小鼠模型用55 mg/kg CEP-32496处理2到10小时,抑制57%到75%pMEK.CEP-32496在多种临床前物种中口服生物可利用(大鼠,狗和猴子> 95%).100 mg/kg CEP-32496处理导致裸鼠中的BRAF(V600E)结肠癌异种移植物中的pMEK和pERK的抑制和持续的肿瘤停滞和退化.CEP-32496在小鼠,狗,猴和人肝微粒体制剂中表现出良好的稳定性,在所有测定中测得的固有清除率值<23(μL/分钟)/ mg和t1/2> 60分钟. |
体内活性 | CEP-32496抑制人类黑素瘤和结直肠癌细胞系中的MAPK/MEK磷酸化,IC50为78 nM和60 nM。CEP-32496抑制A375细胞(BRAFV600E) 增殖,EC50为78 nM。CEP-32496作用于肿瘤细胞系,对表达突变型BRAF的A375,SK-MEL-28,Colo-205,Colo-679和HT-144细胞比表达野生型BRAF的HCT116,Hs578T,LNCaP,DU145和PC-3细胞具有更敏感的细胞毒性作用。 |
激酶实验 | Binding assay: Kinases are produced displayed on T7 phage or by expression in HEK-293 cells and tagged with DNA. Binding reactions are performed at room temperature for 1 hour, and the fraction of kinase not bound to test compound is determined by capture with an immobilized affinity ligand and quantitation by quantitative PCR. Each kinase is tested individually against CEP-32496. Kd values are determined using eleven serial 3-fold dilutions and presented as mean values from experiments performed in duplicate. Variability between individual values is less than 2-fold. |
细胞实验 | Cells are seeded at 104 cells per well in DMEM with 10% fetal calf serum and allowed to attach. The cells are washed with PBS and switched to DMEM with 0.5% of serum and incubated overnight. CEP-32496 is then added at various concentrations with a final DMSO concentration of 0.5% and incubated for 72 h. At the end of incubation, a Cell Titer Blue is added per instructions, and incubation is continued for 3 hours. Remaining viable cells are quantified by measuring the strength of the fluorescence signal using SoftMax Pro (excitation at 560 nm and emission at 590 nm). IC50 values are derived using a 9-point curve fitted with Igor Pro and are presented as mean values from experiments performed in duplicate. Variability between individual values is less than 2-fold.(Only for Reference) |
别名 | RXDX-105, CEP 32496, CEP-32496, CEP32496 |
分子量 | 517.46 |
分子式 | C24H22F3N5O5 |
CAS No. | 1188910-76-0 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Ethanol: < 1 mg/mL (insoluble or slightly soluble)
DMSO: 9 mg/mL (17.39 mM)
可选溶剂 | 浓度 体积 质量 | 1 mg | 5 mg | 10 mg | 25 mg |
DMSO | 1 mM | 1.9325 mL | 9.6626 mL | 19.3252 mL | 48.3129 mL |
5 mM | 0.3865 mL | 1.9325 mL | 3.865 mL | 9.6626 mL | |
10 mM | 0.1933 mL | 0.9663 mL | 1.9325 mL | 4.8313 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。
Agerafenib 1188910-76-0 Angiogenesis Apoptosis Cytoskeletal Signaling MAPK Tyrosine Kinase/Adaptors c-Kit Bcr-Abl PDGFR Src Raf c-RET RXDX 105 RXDX-105 Inhibitor Raf kinases inhibit CEP 32496 CEP-32496 CEP32496 RXDX105 inhibitor