GNA002 是一种有效，选择性的，共价EZH2抑制剂，对EZH2的IC50为1.1 μM。GNA002 可以特异性，共价结合 EZH2-SET 结构域内的 Cys668，通过 Hsp70 相互作用蛋白 (CHIP) 介导的泛素化的 COOH 末端引发 EZH2 降解。GNA002 有效降低 EZH2 介导的 H3K27 三甲基化，重新激活 polycomb 阻遏复合物 2 (PRC2) 沉默的肿瘤抑制基因。
| 生物活性 | GNA002 is a highly potent, specific and covalentEZH2(Enhancer of zeste homolog 2) inhibitor with anIC50of 1.1 μM. GNA002 can specifically and covalently bind to Cys668 within the EZH2-SET domain, triggeringEZH2degradation through COOH terminus of Hsp70-interacting protein (CHIP)-mediated ubiquitination. GNA002 efficiently reduces EZH2-mediated H3K27 trimethylation, reactivates polycomb repressor complex 2 (PRC2)-silenced tumor suppressor genes[1]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | GNA002 (10 μM; 72 hours) clearly inhibits the proliferation of numerous cancer cell lines with IC50s of 0.070 μM and 0.103 μM for MV4-11 and RS4-11[1].
GNA002 (2 μM; 24 hours) demonstrates an elevated capacity to induce cell death in human cancer cells[1].
GNA002 (0.1-4 μM; 48 hours) efficiently reduces EZH2-mediated H3K27 trimethylation in Cal-27 head and neck cancer cells[1].
Cell Proliferation Assay[1] | Cell Line: | Numerous cancer cell lines | | Concentration: | 10 μM | | Incubation Time: | 72 hours | | Result: | Inhibited the proliferation of numerous cancer cell lines with IC50s of 0.070 μM and 0.103 μM for MV4-11 and RS4-11. |
Apoptosis Analysis[1] | Cell Line: | HN-4 and Cal-27 head and neck cancer cells | | Concentration: | 2 μM | | Incubation Time: | 24 hours | | Result: | Induced cellular apoptosis in human cancer cells. |
Western Blot Analysis[1] | Cell Line: | Cal-27 head and neck cancer cells | | Concentration: | 0.1, 0.2, 0.5, 1, 2, 4 μM | | Incubation Time: | 48 hours | | Result: | Reduced H3K27Me3 levels. |
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体内研究
(In Vivo) | GNA002 (oral administration; 100 mg/kg; daily) significantly decreases the volumes of Cal-27-derived tumors and reduces H3K27Me3 levels in tumor tissues. GNA002 also significantly suppresses the in vivo tumor growth derived from the xenografted A549 lung cancer cells, Daudi and Pfeiffer cells. GNA002 inhibits the aberrant oncogenic functions of EZH2, thus inhibiting tumor growth in vivo, at least in the xenograft experimental model[1].
| Animal Model: | Male BALB/C Nude mice aged 30-35 days and weighing 18-22 g, bearing Cal-27 xenograft tumors[1] | | Dosage: | 100 mg/kg | | Administration: | Oral administration; daily | | Result: | Decreased the size and weight of tumors formed by Cal-27 cells. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, stored under nitrogen *In solvent : -80°C, 6 months; -20°C, 1 month (stored under nitrogen) |
| 溶解性数据 | In Vitro: DMSO : 25 mg/mL(35.62 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.4247 mL | 7.1236 mL | 14.2472 mL | | 5 mM | 0.2849 mL | 1.4247 mL | 2.8494 mL | | 10 mM | 0.1425 mL | 0.7124 mL | 1.4247 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；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (stored under nitrogen)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro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，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制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 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 1.25 mg/mL (1.78 mM); Clear solution
此方案可获得 ≥ 1.25 mg/mL (1.78 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90% (20%SBE-β-CDin saline) Solubility: 1.25 mg/mL (1.78 mM); Suspended solution; Need ultrasonic
此方案可获得 1.25 mg/mL (1.78 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。 以 1 mL 工作液为例，取 100 μL 12.5 mg/mL 的澄清 DMSO 储备液加到 900 μL20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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