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Ro 5126766 (Synonyms: CH5126766) 纯度: 98.19%
Ro 5126766 (CH5126766) 是一种有效的双重 MEK/RAF 抑制剂,抑制 BRAFV600E,CRAF, MEK,和 BRAF,IC50 分别为 8.2 nM, 56 nM, 160 nM 和 190 nM。
Ro 5126766 Chemical Structure
CAS No. : 946128-88-7
规格 | 价格 | 是否有货 | 数量 |
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10 mM * 1 mL in DMSO | ¥1760 | In-stock | |
5 mg | ¥1600 | In-stock | |
10 mg | ¥2600 | In-stock | |
50 mg | ¥9600 | In-stock | |
100 mg | ¥12000 | In-stock | |
200 mg | 询价 | ||
500 mg | 询价 |
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生物活性 |
Ro 5126766 (CH5126766) is a first-in-class dual MEK/RAF inhibitor that allosterically inhibits BRAFV600E, CRAF, MEK, and BRAF (IC50: 8.2, 56, 160 nM, and 190 nM, respectively). |
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IC50 & Target[1] |
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体外研究 (In Vitro) |
Ro 5126766 (RO5126766) is an allosteric inhibitor that binds directly to MEK and prevents its phosphorylation by RAF through the formation of a stable RAF-MEK complex. Ro 5126766 inhibits both the phosphorylation of MEK by RAF and the activation of ERK by MEK. In cell-free MEK and RAF kinase assays, Ro 5126766 effectively inhibits activation of ERK2 by MEK1 with an IC50 of 160 nM (SD=±0.043) and inhibits the phosphorylation of MEK1 protein by BRAF (IC50=190 nM, SD=±0.003), BRAFV600E (IC50=8.2 nM, SD=±0.0015), and CRAF (IC50=56 nM, SD=±0.016). Ro 5126766 effectively inhibits both MEK and ERK phosphorylation in a panel of human tumor cell lines including KRAS/HRAS and BRAF mutant cell lines and KRAS/HRAS and BRAF wild-type cells[1]. In order to investigate whether the mevalonate pathway affects the sensitivity to MEK inhibitors, human breast cancer MDA-MB-231 cells harboring KRAS and BRAF mutations are treated Ro 5126766 (CH5126766), with or without statins, which inhibits HMG-CoA reductase, the rate-limiting enzyme in the mevalonate pathway. The combined treatment of Ro 5126766 with XU 62-320 demonstrates more significant reduction in cell growth in a dose-dependent manner than the single treatment of Ro 5126766. The marked combined effects of Ro 5126766 at 40 nM and XU 62-320 at 0.3 μM is also confirmed on the suppression of the colony formation of the cells[2]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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体内研究 (In Vivo) |
In KRAS-mutant xenograft models, Ro 5126766 (RO5126766) inhibits growth and causes tumor regressions more effectively than another allosteric MEK inhibitor, PD0325901. Preclinical data from a series of human tumor mouse xenograft models indicates an ED50 for Ro 5126766 of 0.03 to 0.23 mg/kg and an ED90 of 0.15 to 1.56 mg/kg. These effective doses are associated with target trough concentrations of 17 to 133 ng/L and 87 to 901 ng/mL, respectively. [1]. In this experiment, Ro 5126766 (CH5126766) or PD0325901 is administrated at their maximum tolerated dose (MTD) in the HCT116 model (1.5 and 25 mg/kg, respectively). These doses inhibit pERK and ERK signaling output at similar degrees in the tumors from the drug-treated mice at 4 hours from the first drug administration. Moreover, in HCT116 models, the ED50 for Ro 5126766 and PD0325901 are 0.056 and 0.80 mg/kg, respectively. Therefore, the doses used for this experiment are 26.8- and 31.3-fold higher doses than the 50% effective doses, respectively. Daily oral administration of either drug causes significant tumor regression of each these tumors. However, whereas inhibition of tumor growth is maintained for the entire 28-day treatment period in Ro 5126766-treated mice, tumor models receiving PD0325901 become refractory after 10 days of treatment[3]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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Clinical Trial |
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分子量 |
471.46 |
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Formula |
C21H18FN5O5S |
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CAS 号 |
946128-88-7 |
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运输条件 |
Room temperature in continental US; may vary elsewhere. |
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储存方式 |
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溶解性数据 |
In Vitro:
DMSO : 250 mg/mL (530.27 mM; Need ultrasonic) 配制储备液
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请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。 In Vivo:
请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议您现用现配,当天使用; 以下溶剂前显示的百
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参考文献 |
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Cell Assay [2] |
The number of viable cells is assessed with a Cell Counting Kit-8 assay. Human breast cancer MDA-MB-231 cells, human melanoma SK-MEL-28 cells, and human non-small cell lung cancer A549 cells are seeded at a density of 2,000 cells per well in 96-well plates and incubated for 24 h, and then treated with Ro 5126766 (10, 20, 40, and 80 nM) for 72 h. After a further 4 h incubation with the kit reagent, the absorbance at 450 nm of the samples is measured using a multi-plate reader[2]. 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
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Animal Administration [3] |
Mice[3] 上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only. |
参考文献 |
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