ZCL278 - Ras 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEZCL278Cat. No.: HY-13963CAS No.: 587841-73-4分式: CHBrClNOS分量: 584.89作靶點: 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)體外實驗 DMSO : 50 mg/mL (85.49 mM; Need ultrasonic)Mass Solven

2、t1 mg 5 mg 10 mg Concentration制備儲備液1 mM 1.7097 mL 8.5486 mL 17.0972 mL5 mM 0.3419 mL 1.7097 mL 3.4194 mL10 mM 0.1710 mL 0.8549 mL 1.7097 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內(nèi)實驗 請根據(jù)您的實驗動物和給藥式選擇適當(dāng)?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結(jié)果的可靠性，體內(nèi)實驗的作液，建議您現(xiàn)現(xiàn)配，當(dāng)天使；澄清的儲備液可以根據(jù)儲存條件，適當(dāng)保存；以下溶劑前的百分 指該溶劑在您配

3、制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.27 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.27 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE物活性 ZCL278種選擇性的 Cdc42 調(diào)節(jié)劑，直接結(jié)合到 Cdc4

4、2，且抑制其功能，Kd 為 11.4 M。IC50 & Target Kd: 11.4 M (Cdc42) 1體外研究 ZCL278 as a potent, cell-permeable Cdc42-specific inhibitor that suppresses actin-based cellular functions,including Golgi organization and cell motility.In Swiss 3T3 fibroblast cultures, ZCL278 abolishes microspikeformation and disrupted G

5、M130-docked Golgi structures, two of the most prominent Cdc42-mediatedsubcellular events. ZCL278 reduces the perinuclear accumulation of active Cdc42 in contrast to NSC23766,a selective Rac inhibitor. ZCL278 suppresses Cdc42-mediated neuronal branching and growth conedynamics as well as actin-based

6、motility and migration in a metastatic prostate cancer cell line (i.e., PC-3)without disrupting cell viability 1. ZCL278 inhibits Cdc42 function as an entry inhibitor for Junin virus (JUNV)and for vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus but not for thenonenve

7、loped poliovirus. In cells, ZCL278 is shown to efficiently inhibit chemically induced filopodiumformation, a process dependent on Cdc42 activity. Dose-response experiments are first carried out in Verocells, and while ZCL278 is not toxic at concentrations up to 200 M, ZCL278 inhibits JUNV with IC50

8、of 14M, as measured by flow cytometry 2.體內(nèi)研究 ZCL278 reduces the JUNV RNA load in the spleen more than 33-fold, with JUNV RNA being undetectable in5 out of 8 mice. These results are similar to those seen in Gabapentin-treated mice, demonstrating thatZCL278 can abrogate JUNV replication 2.PROTOCOLKina

9、se Assay 1 Lyophilized Cdc42 protein is reconstituted to 5 mg/mL in a buffer consisting of 50 mM Tris, 0.5 mM MgCl2,50 mM NaCl, 3% (wt/vol) sucrose, and 0.6% dextran. The stock solution is then diluted to 1 M in 5 mMphosphate buffer, pH 7.4. Into a quartz cuvettete containing Cdc42 solution, aliquot

10、s of ZCL278 are addedand incubated for 5 min before each fluorescent measurement. The excitation wavelength is 275 nm, and thefluorescence of tryptophan at 350 nm is measured after each addition. The titration curve is fitted using theequimolar specific binding model in GraphPad, and the Kd is calcu

11、lated 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 To determine cell viability, PC-3 cells are incubated for 24 h with or without the Cdc42 activator, ZCL278, orNSC23766. By using the trypan blue dye exclusion method, the numbers of li

12、ve and dead cells are obtainedwith a Countess Automated Cell Counter. P values are assigned in each experiment, and any null hypothesiswith probability level 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Four-week-old C

13、57BL/6 mice receive intravenous injections of Gabapentin or ZCL278 (100 g/g, i.p.). At 1 hafter treatment, the mice are inoculated intraperitoneally with JUNV Candid #1 (1106 PFU) in no more than1 mL with a 27 1/2-gauge needle. At the end of the experiment, the mice are sacrificed, their spleens are

14、homogenized with a Dounce homogenizer and centrifuged to generate a cell pellet and supernatant, andRNA expression levels are determined.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Cell Mo

15、l Immunol. 2019 Jun 3.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Friesland A, et al. Small molecule targeting Cdc42-intersectin interaction disrupts Golgi organization and suppresses cell motility. ProcNatl Acad Sci U S A. 2013 Jan 22;110(4):1261-6.2. Chou YY, et al. Identification and Characterization of a Novel Broad-Spectrum Virus Entry Inhibitor. J Virol