1A-116 - Ras 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemE1A-116Cat. No.: HY-104064CAS No.: 1430208-73-3分式: CHFN分量: 307.31作靶點(diǎn): Ras作通路: GPCR/G Protein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(shí)驗(yàn) DMSO : 100 mg/mL (325.40 mM; Need ultrasonic)H2O : 40% PE

2、G300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (8.14 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.5 mg/mL (8.14 mM); Suspended solution; Need ultrasonic3. 請依序添加每種溶劑： 10% DMSO 90% corn oil1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemESolubility: 2.5 mg/mL (8.

3、14 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 1A-116種特異性 Rac1 抑制劑。IC50 & Target Rac1 1體外研究 1A-116 shows lesser effect on MCF7:pcDNA.3 cells than on MCF7:C1199 cells. 1A-116 treatmentdecreases phospho-PAK1 levels in a time-dependent manner. The presence of 1A-116 reverts the PAK1phosphorylation induce

4、d by 4-hydroxytamoxifen (Tam). The presence of 1A-116 also effectively revertsRac1-PAK1-mediated estrogen receptor (ER) phosphorylation at Ser305 1. 1A-116 shows a significantincrease in antiproliferative activity on F3II cells, showing an IC50 value of 4 M. A-116 also dramaticallyimpairs Rac1 activ

5、ation at low micromolar range (1 M) 2.體內(nèi)研究 Daily treatment of mice with compound 1A-116 at 3mg/kg body weight/day reduces about 60% the formationof total metastatic lung colonies. A significant antitumor activity is obtained for macronodules (more than 1mm in diameter) by treatment with 1A-116 in th

6、is highly aggressive breast cancer model. The treatment with1A-116 reduces the total lung weight compare to the control group, leading to a total weight similar to theaverage pulmonary weight of Balb/c mice 2.PROTOCOLCell Assay 1 5103 MCF7:pcDNA.3 and MCF7:C1199 cells are plated in 96-wells plates a

7、nd 24 hours later are treatedfor 72 hours with different concentrations of 17-Estradiol to evaluate hormone response. To evaluate thereversion of 4-hydroxytamoxifen (Tam) resistance by 1A-116, MCF7:C1199 cells are treated with Tam (0.01M, 0.1 M and 1 M), 1A-116 (4 M) or combination of both for 72 ho

8、urs. Cell growth is measured bycolorimetric crystal violet assay. The analysis of hormone-dependent growth and Tam resistance reversion isdetermined using PRISM 6, Version 6.01. Results shown correspond to the average of three independentexperiments 1.MCE has not independently confirmed the accuracy

9、 of these methods. They are for reference only.Animal Specific pathogen-free female BALB/c inbred mice with an age of 8 to 10 weeks and an average weight of 20Administration 2 g, are used. They are housed in plastic cages under standard conditions and have access to rodent chowand water ad libitum.

10、On day 0, 2105 viable F3II cells in 0.3 mL Dulbeccos modified Eagle medium(DMEM) are injected into the lateral tail vein. Mice are injected i.p at daily doses of 3 mg/kg body weight 1A-116 or vehicle. Treatment is carried out from day 0 to day 21. On day 21 mice are sacrificed and lungs areexcised a

11、nd immediately fixed in Bouins solution. Superficial lung nodules are counted under dissectionmicroscope 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE1. Gonzalez N, et al. Pharmacological i

12、nhibition of Rac1-PAK1 axis restores tamoxifen sensitivity in human resistant breast cancer cells.Cell Signal. 2017 Jan;30:154-161.2. Cardama GA, et al. Preclinical development of novel Rac1-GEF signaling inhibitors using a rational design approach in highlyaggressive breast cancer cell lines. Anticancer Agents Med Chem. 2014;14(6):840-51.McePdfHeightCaution: