MBQ-167 - Ras 抑制劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMBQ-167Cat. No.: HY-112842CAS No.: 2097938-73-1分式: CHN分量: 338.41作靶點: Ras; CDK作通路: GPCR/G Protein; Cell Cycle/DNA Damage儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 155 mg/mL (458.02 mM;

2、Need ultrasonic)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.58 mg/mL (7.62 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.58 mg/mL (7.62 mM); Clear solution; Need warming1/2 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 MBQ-167Ras 相關的 C3 型毒素底物 (Rac

3、) 和細胞分裂周 期蛋 (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。IC50 & Target Cdc42 Ras 1/2/378 nM (IC50) 103 nM (IC50)體外研究 MBQ-167 (100 nM) induces a loss of polarity in metastatic breast cancer cells. Treatment with 500 nMMBQ-167 for 24 h results in 95% cell rounding and detachment

4、 from the substratum in metastatic MDA-MB-231 cells. Moreover, MBQ-167 induces this phenotype in multiple mesenchymal cancer cell types includingGFP-HER2-BM, MDA-MB-468, and Hs578t human breast cancer cells, as well as Mia-PaCa-2 pancreaticcancer cells, SKOV3 ovarian cancer cells, AGS and NCI-N87 ga

5、stric cancer cells, and SH-SY5Yneuroblastoma 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 responsivewith a 75% decrease. At earlier times (6h), treatment with 250 or

6、 500 nM MBQ-167, induce a inhibition inRac activity in the attached cell population, while the detached population demonstrate a 40-50% inhibition1.體內(nèi)研究 MBQ-167-treated mice demonstrate a statistically significant reduction in tumor growth. At sacrifice, 1.0mg/kg BW of MBQ-167 results in a 80% reduc

7、tion in tumor growth, and the 10 mg/kg BW MBQ-167treatment results in 95% reduction in tumor growth. Since EHop-016 only exerts 40% reduction of tumorgrowth at 10 mg/kg BW, MBQ-167 is 10X more effective than EHop-016. MBQ-167 treated mice demonstratesimilar doubling times for both treatments (10 and

8、 11 days) 1.PROTOCOLAnimal Mice 1Administration 1 Female athymic nu/nu mice, 4 to 5wk old are used. GFP-HER2-BM cells (5105) in Matrigel are injected atthe fourth right mammary fat pad under isofluorane inhalation to produce orthotopic primary tumors. Aftertumor establishment (1wk post-inoculation),

9、 animals are randomly divided into treatment groups (n=6). Miceare treated with vehicle (12.5% ethanol, 12.5% Cremophor, and 75% 1X PBS pH 7.4), or 1 or 10 mg/kg BWMBQ-167 by i.p. injection in a 100 L volume 3X a wk. Treatments continue until sacrifice at day 65 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Humphries-Bickley T, et al. Characterization of a Dual Rac/Cdc42 Inhibitor MBQ-167 in Metastatic Cancer. Mol Cancer Ther. 2017May;16(5):805-818.McePdfHeightCaution: Product has not been fully validate