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MBQ-167
產(chǎn)品活性:MBQ-167 是 Ras 相關(guān)的 C3 型肉毒素底物 (Rac) 和細(xì)胞分裂周期蛋白 (Cdc42) 的雙抑制劑,其對 Rac 1/2/3 的 IC50 值為 103 nM, 對 Cdc42 的 IC50 值為 78 nM。
研究領(lǐng)域:GPCR/G Protein | Cell Cycle/DNA Damage
作用靶點(diǎn):Ras | CDK
In Vitro: MBQ-167 (≥100 nM) induces a loss of polarity in metastatic breast cancer cells. Treatment with 500 nM MBQ-167 for 24 h results in ~95% cell rounding and detachment from the substratum in metastatic MDA-MB-231 cells. Moreover, MBQ-167 induces this phenotype in multiple mesenchymal cancer cell types including GFP-HER2-BM, MDA-MB-468, and Hs578t human breast cancer cells, as well as Mia-PaCa-2 pancreatic cancer cells, SKOV3 ovarian cancer cells, AGS and NCI-N87 gastric cancer cells, and SH-SY5Y neuroblastoma cells. Following treatment with 250 nM MBQ-167 for 24 h, the attached population of MDA-MB-231 cells demonstrate a ~25% decrease in Rac activation while the detached cells are more responsive with a ~75% decrease. At earlier times (6h), treatment with 250 or 500 nM MBQ-167, induce a inhibition in Rac activity in the attached cell population, while the detached population demonstrate a ~40-50% inhibition.
In Vivo: MBQ-167-treated mice demonstrate a statistically significant reduction in tumor growth. At sacrifice, 1.0 mg/kg BW of MBQ-167 results in a ~80% reduction in tumor growth, and the 10 mg/kg BW MBQ-167 treatment results in ~95% reduction in tumor growth. Since EHop-016 only exerts ~40% reduction of tumor growth at 10 mg/kg BW, MBQ-167 is 10X more effective than EHop-016. MBQ-167 treated mice demonstrate similar doubling times for both treatments (10 and 11 days).
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