现货,AZD6244 (Selumetinib) ,目录号 S1008 ,CAS号:606143-52-6, 942275-12-9 (4-methylbenzenesulfonate),MAPK, MEK 抑制剂,美国进口,Selleck
价格: ¥2268
产品详情
文献和实验
相关推荐
保存条件 :零下二十摄氏度低温保存
CAS号 :CAS号: 606143-52-6, 942275-12-9 (4-methylbenzenesulfonate)
英文名 :AZD6244 (Selumetinib)
保质期 :两年
库存 :大量
供应商 :美国Selleck南京办事处
规格 :5mg
技术数据:
分子量(MW): | 457.68 | |
---|---|---|
化学式: | C17H15BrClFN4O3 |
|
溶解度: | DMSO ≥92mg/mL Water <1mg/mL Ethanol <1mg/mL | |
纯度: | >99% | |
稳定性: | at -20℃ 2 years | |
CAS号: | 606143-52-6, 942275-12-9 (4-methylbenzenesulfonate) |
生物活性
AZD6244非常有效地抑制MEK1,IC50为14nM。AZD6244是ATP非竞争性的抑制剂,在IC50浓度小于40 nM时使ERK1/2的磷酸化作用失活。AZD6244也通过抑制ERK1/2和p90RSK的磷酸化抑制原代HCC细胞的生长,同时伴随着caspase-3和caspase-7分裂的加强, 及断裂的聚腺苷二磷酸核糖聚合酶的增多。[1] AZD6244对感知乳腺癌细胞系中的raf突变和非小细胞肺癌细胞系中的ras突变很灵敏[2]。AZD6244在P38,JNK,PI3K,及MEK5/ERK5通路中的作用不大。活体研究显示AZD6244在2-1318, 5-1318, 及26-1004 4-1318移植物中明显抑制ERK1/2的磷酸化,并且在原代2-1318细胞中通过激活caspase通路诱导细胞凋亡。[1] HT-29 移植瘤是携带B-raf突变的直肠瘤模型,AZD6244 在100mg/kg剂量时可以抑制HT-29移植瘤中肿瘤的增长,并且 AZD6244作用下的肿瘤指数比吉西他滨作用下的肿瘤指数要好。[3] 另外,AZD6244可以抑制HCC移植瘤的增长,HCC移植瘤的增长与细胞凋亡的增多,及细胞周期调控的减量调节有关。包括:cyclin D1, cdc-2, CDK 2 ,CDK4, cyclin B1, 及 c-Myc。 [4] AZD6244可以用于治疗多种癌症,包括直肠癌,非小细胞肺癌,胰腺癌,乳腺癌等。AZD6244用于治疗非小细胞肺癌目前还处在二期临床试验阶段。AZD6244最初是由Array BioPharma研究的,目前由Astra Zeneca在研究。
参考文献
[1]
[2]
[3]
[4]
客户反馈数据
INA-6 MM cells were treated with AS703026 or AZD6244 for 2 d, followed by [3H]thymidine uptake assay. PBMCs isolated from normal donors (n = 3) were incubated with M-CSF and RANKL, in the presence or absence of AS703026 or AZD6244 for 14 d. The TRAP assay was performed to measure the formation of multinuclear osteoclast cells (OC). |
|
AZD6244 enhanced FOXO3a expression and induced suppression of cancer cell proliferation. A, tumor volume of the HCT116 xenografts treated with Placebo or AZD6244 was measured for 21 d. The tumor sections of four individual DMSO or AZD6244-treated HCT116 xenografts were subjected to immunohistochemistry with a FOXO3a antibody. Relative percentages of nuclear FOXO3a expression of individual xenograft tumors from B were analyzed and the mean values of FOXO3a expression in Placebo or AZD6244-treated group were indicated as bars. |
|
lysates from various cancer cell lines: breast cancer (MDA-MB-435), colon cancer (HCT116, SW620, and HT29), and melanoma (WM793) treated with DMSO or AZD6244 (10 μmol/L) for 4 h were subjected to immunoblotting with the indicated antibodies.
|
|
B-RafV600E mutated melanoma line,A375, was treated with different doses of AZD6244 for 1hour or 24 hours.Cell lysates were analyzed by Western Blotting to determine the levels of phosphorylated ERK1/2(Perk1/2)
|
|
A,ERK phosphorylation in A375 expressing indicated ORFs following treatment with DMSO or 1 mM of PLX4720, RAF265, CI-1040 or AZD6244. B,ERK phosphorylation in A375 expressing indicated ORFs following treatment with DMSO, PLX4720 (1 mM) or PLX4720 in combination with CI-1040 or AZD6244 (all 1 mM). |
|
Ex vivo and functional characterization of MEK1(P124L). (A) AZD6244-mediated growth inhibition ex vivo of treatment-naïve BRAFV600E melanoma cells (black and blue) or cells cultured from an AZD6244-resistant metastatic focus (red). (B) ERK phosphorylation (p-ERK) andMEKphosphorylation (p-MEK) are shown following treatment with increasing concentrations of AZD6244 in treatment-naïve or AZD6244-resistant melanoma cells cultured ex vivo. The tubulin loading control (-tubulin) is also shown. (C) AZD6244 growth inhibition curves of parental A375 (solid black), A375 cells expressing MEK-DD (grey), wild-type MEK1 (hatched black), or MEK1(P124L) (red) are shown. In each instance n6 anderrorstandard deviation. (D) p-ERK and p-MEK are shown following treatment with increasing AZD6244 concentrations in the cell lines described in C, Above. The -tubulin control is also shown.
|
|
A and B, clonogenic assays in 2 melanoma cell lines (YUVON and YUSIK) treated with NVPBEZ235 (BEZ) and AZD6244 (AZD) alone and in combination. Combinations were more effective in inhibiting colony formation at lower concentrations than either drug alone. |
|
Survival curves for isogenic cell line pairs and melanoma cultures treated with the indicated AZD6244 concentration for 72 h (relative to DMSO treated controls; mean6s.e.m., n55). PLX4032 resistant cells were grown with PLX4032. Dashed line, 50% cell killing. |
特定的存储和包装每个产品的信息在产品说明书上都有注明 。大多数Selleck产品,在推荐的条件下存储可稳定保存两年。产品有时建议的储存温度不同,大多数建议储存在-20 ° C ,抗体及蛋白等产品建议-60℃。抑制剂属于化学试剂,可在常温下运输储存两周左右。即使如此,我们保证产品的出货量将保持产品质量的条件下,一般都会放入冰袋。望阁下收到产品后,请按照产品数据表建议适当存储。