ZCL278 - Ras 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEZCL278Cat. No.: HY-13963CAS No.: 587841-73-4分式: CHBrClNOS分量: 584.89作靶点: Ras作通路: GPCR/G Protein储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (85.49 mM; Need ultrasonic)Mass Solven

2、t1 mg 5 mg 10 mg Concentration制备储备液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，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配

3、制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (4.27 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (4.27 mM); Clear solutionBIOLOGICAL ACTIVITY1/3 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 ZCL278种选择性的 Cdc42 调节剂，直接结合到 Cdc4

4、2，且抑制其功能，Kd 为 11.4 M。IC50 & Target Kd: 11.4 M (Cdc42) 1体外研究 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.体内研究 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 您边的抑制剂师www.MedChemEMCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 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