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| 靶点 |
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| 描述 | ZCL278 is a potent, cell-permeable inhibitor specific to Cdc42, suppressing actin-based cellular functions such as Golgi organization and cell motility. In Swiss 3T3 fibroblast cultures, ZCL278 disrupts microspike formation and GM130-docked Golgi structures, prominent Cdc42-mediated subcellular events. It reduces perinuclear accumulation of active Cdc42 compared to NSC23766, a selective Rac inhibitor. ZCL278 also inhibits Cdc42-mediated neuronal branching, growth cone dynamics, actin-based motility, and migration in PC-3 metastatic prostate cancer cells without impacting cell viability [1]. ZCL278 acts as an entry inhibitor for Junin virus (JUNV), vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus, but not for nonenveloped poliovirus. It efficiently inhibits chemically induced filopodium formation, a process dependent on Cdc42 activity. Dose-response experiments in Vero cells show that ZCL278, up to 200 μM, is not toxic but inhibits JUNV with an IC50 of ~14 μM, measured by flow cytometry [2]. |
| 体内研究 | ZCL278 decreases JUNV RNA load in the spleen over 33-fold, with JUNV RNA undetectable in 5 out of 8 mice, similar to Gabapentin-treated mice, indicating ZCL278's ability to halt JUNV replication [2]. |
| 体外研究 | ZCL278 is a potent, cell-permeable inhibitor specific to Cdc42, suppressing actin-based cellular functions such as Golgi organization and cell motility. In Swiss 3T3 fibroblast cultures, ZCL278 disrupts microspike formation and GM130-docked Golgi structures, prominent Cdc42-mediated subcellular events. It reduces perinuclear accumulation of active Cdc42 compared to NSC23766, a selective Rac inhibitor. ZCL278 also inhibits Cdc42-mediated neuronal branching, growth cone dynamics, actin-based motility, and migration in PC-3 metastatic prostate cancer cells without impacting cell viability [1]. ZCL278 acts as an entry inhibitor for Junin virus (JUNV), vesicular stomatitis virus, lymphocytic choriomeningitis virus, and dengue virus, but not for nonenveloped poliovirus. It efficiently inhibits chemically induced filopodium formation, a process dependent on Cdc42 activity. Dose-response experiments in Vero cells show that ZCL278, up to 200 μM, is not toxic but inhibits JUNV with an IC50 of ~14 μM, measured by flow cytometry [2]. |
| 作用机制 | ZCL278 is a small molecule that binds to Cdc42 residues to target the interaction between Cdc42 and intersectin and inhibits Cdc42-mediated cellular processes. |
| Concentration | Treated Time | Description | References | |
| PC3 prostate cancer cells | 20 µM | 48, 96, 144 hours | Inhibited cell proliferation | Cancer Biol Ther. 2019;20(6):740-749. |
| A549 lung cancer cells | 50 µM | 48, 96, 144 hours | Inhibited cell proliferation | Cancer Biol Ther. 2019;20(6):740-749. |
| Swiss 3T3 cells | 0.01, 0.1, 1, 10, 50, 100 µM | 15 minutes | ZCL278 promoted Cdc42 activation | Commun Chem. 2024 Nov 19;7(1):271. |
| Swiss 3T3 cells | 50 µM | 2 hours | Activated Cdc42 and promoted microspike formation | Cancer Biol Ther. 2019;20(6):740-749. |
| LNCaP prostate cancer cells | 20 µM | 48, 96, 144 hours | Inhibited cell proliferation | Cancer Biol Ther. 2019;20(6):740-749. |
| Capan-1 | 1, 5, and 20 µM | 10 minutes | To assess the inhibitory effect of ZCL278 on Cdc42 function, results showed that ZCL278 decreased Cdc42 activity in a dose-dependent manner and inhibited microspike formation and stress fibers | Cell Prolif. 2020 Apr;53(4):e12799. |
| PANC-1 | 1, 5, and 20 µM | 10 minutes | To assess the inhibitory effect of ZCL278 on Cdc42 function, results showed that ZCL278 decreased Cdc42 activity in a dose-dependent manner and inhibited microspike formation and stress fibers | Cell Prolif. 2020 Apr;53(4):e12799. |
| Swiss 3T3 cells | 50 µM | 10, 20, 30, 60, 120, 360 minutes | ZCL278 at 50 µM formed an initial peak at 10 minutes. ZCL278 then displayed an antagonistic effect at 30 minutes followed by resuming a strong agonistic effect up to 6 hours without showing the plateau | Commun Chem. 2024 Nov 19;7(1):271. |
| Swiss 3T3 fibroblasts | 50 µM | 15 min or 1 hour | Inhibited Cdc42-mediated microspike formation without affecting RhoA-mediated stress fibers | Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1261-6. |
| SVG-A cells | 50 µM | 30 minutes | ZCL278 inhibited JUNV infection without affecting cell viability. | J Virol. 2016 Apr 14;90(9):4494-4510. |
| Vero cells | 50 µM | 30 minutes | ZCL278 inhibited JUNV infection with an IC50 of ∼14 μM and showed no cytotoxicity. | J Virol. 2016 Apr 14;90(9):4494-4510. |
| Primary neonatal cortical neurons | 50 µM | 5 and 10 min | Inhibited neuronal branching and growth cone dynamics | Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1261-6. |
| PC-3 prostate cancer cells | 50 µM | 5, 10, and 15 min | Inhibited Cdc42 activity and increased Rac/Cdc42 phosphorylation | Proc Natl Acad Sci U S A. 2013 Jan 22;110(4):1261-6. |
| Human Umbilical Cord Sca-1+ Progenitor Cells (HUCSCs) | 10 µM | CDC42 inhibitor ZCL278 partially blocked Meox1-mediated enhancement of Sca-1+ progenitor cell migratory capacity | Stem Cell Res Ther. 2021 Jul 7;12(1):387. | |
| Vascular Smooth Muscle Cells (VSMC) | 10 µM | CDC42 inhibitor ZCL278 significantly attenuated Meox1 overexpression-induced upregulation of SDF-1α in VSMCs | Stem Cell Res Ther. 2021 Jul 7;12(1):387. | |
| Administration | Dosage | Frequency | Description | References | ||
| C57BL/6 mice | JUNV infection model | Intraperitoneal injection | 100 μg/g | Once daily for 4 days | ZCL278 significantly reduced JUNV RNA load in the spleen and showed no toxicity. | J Virol. 2016 Apr 14;90(9):4494-4510. |
| 3xTg-AD mice | Alzheimer's disease model | Intraperitoneal injection | 20 µg/g | Every other day for four weeks | ZCL278 ameliorated Alzheimer’s disease-like social behavior | Commun Chem. 2024 Nov 19;7(1):271. |
| BALB/c-nu mice | HCC lung metastasis model | Intraperitoneal injection | 20 mg/kg | Every other day for 28 days | To evaluate the inhibitory effect of ZCL278 on HCC lung metastasis | J Exp Clin Cancer Res. 2022 Jul 22;41(1):230 |
| Dose | Mice: 0.8 mg/g[3] (i.p.) |
| Administration | i.p. |
| 计算器 | ||||
| 存储液制备 | ![]() |
1mg | 5mg | 10mg |
|
1 mM 5 mM 10 mM |
1.71mL 0.34mL 0.17mL |
8.55mL 1.71mL 0.85mL |
17.10mL 3.42mL 1.71mL |
|
| CAS号 | 587841-73-4 |
| 分子式 | C21H19BrClN5O4S2 |
| 分子量 | 584.89 |
| SMILES Code | O=C(NC(NC1=CC=C(S(=O)(NC2=NC(C)=CC(C)=N2)=O)C=C1)=S)COC3=CC=C(Br)C=C3Cl |
| MDL No. | MFCD03623090 |
| 别名 | |
| 运输 | 蓝冰 |
| InChI Key | XKZDWYDHEBCGCG-UHFFFAOYSA-N |
| Pubchem ID | 1791111 |
| 存储条件 |
In solvent -20°C: 3-6个月 -80°C: 12个月 Pure form Sealed in dry, 2-8°C |
| 溶解方案 |
DMSO: 50 mg/mL(85.49 mM),配合低频超声助溶,注意:DMSO长时间开封后,会吸水并导致溶解能力下降,请避免使用长期开封的DMSO 以下溶解方案都请先按照体外实验的方式配制澄清的储备液,再依次添加助溶剂: ——为保证实验结果的可靠性,澄清的储备液可以根据储存条件,适当保存;体内实验的工作液,建议现用现配,当天使用; 以下溶剂前显示的百分比是指该溶剂在终溶液中的体积占比;如在配制过程中出现沉淀、析出现象,可以通过加热和/或超声的方式助溶
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