| 產(chǎn)品描述： | LGX818 is an orally available mutated BRaf V600E inhibitor(IC50=0.3 nM) with potential antineoplastic activity. |
| 靶點(diǎn)： |
Raf |
| 體內(nèi)研究： |
LGX818 treatment at oral doses as low as 6 mg/kg resulted in strong (75%) and sustained (>24 hours) decrease in phospho-MEK, even following clearance of drug from circulation in single dose PK/PD studies in human melanoma xenograft models (BRAFV600E). LGX818 induces tumor regression in multiple BRAF mutant human tumor xenograft models grown in immune compromised mice and rats at doses as low as 1 mg/kg. Consistent with the in vitro data, LGX818 is inactive against BRAF wild-type tumors at doses up to 300 mg/kg bid, with good tolerability and linear increase in exposure. Efficacy is also achieved in a more disease-relevant spontaneous metastatic melanoma and a model of melanoma brain metastasis. LGX818 is a potent and selective RAF kinase inhibitor with unique biochemical properties that contribute to an excellent pharmacological profile. |
| 細(xì)胞實(shí)驗(yàn)： |
LGX818 is dissolved in DMSO. A375 is a melanoma cell line that harbors the B-Raf V600E mutation. A375-luc cells engineered to express luciferase is plated to 384-well white clear bottom plates as 1,500 cells/50 μL/well in DMEM containing 10% FBS. Test compounds, dissolved in 100% DMSO at appropriate concentrations, are transferred to the cells by a robotic Pin Tool (100 mL). The cells are incubated for 2 days at 25°C, then 25 μL of BrightGloTM is added to each well and the plates are read by luminescence. The concentration of each compound for 50% inhibition (IC50) is calculated by non-linear regression using XL Fit data analysis software. wild type and V600E B-Raf. |
| 參考文獻(xiàn)： |
1.Darrin D Stuart, et al. Cancer Res, 2012, 72(8 Supplement): 3790 |
| 溶解性： |
Ethanol:93 mg/mL (172.2 mM) DMSO:93 mg/mL (172.2 mM) H2O:<1 mg/mL |
| 保存條件： |
2-8℃ |
| 配置溶液濃度參考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.852 ml |
9.259 ml |
18.518 ml |
| 5 mM |
0.37 ml |
1.852 ml |
3.704 ml |
| 10 mM |
0.185 ml |
0.926 ml |
1.852 ml |
| 50 mM |
0.037 ml |
0.185 ml |
0.37 ml |
|
| 注意： |
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