Vimentin-IN-1 是 FiVe1 衍生物，是一种口服有效的选择性抗癌剂。FiVe1 能够结合 III 型中间丝蛋白vimentin(VIM)，诱导 Ser56 过度磷酸化，导致有丝分裂的选择性中断和转化表达 VIM 的间充质癌细胞的多核化。Vimentin-IN-1 比 FiVe1 表现出更好的口服利用度和药代动力学特征。
| 生物活性 | Vimentin-IN-1 is a FiVe1 derivative, an orally active and selective anticancer agent. FiVe1 binds type III intermediate filament protein vimentin (VIM), to induce hyperphosphorylation of Ser56, resulting selective disruption of mitosis and multinucleation in transformed VIM-expressing mesenchymalcancercells. Vimentin-IN-1 shows better oral bioavailability and pharmacokinetic profiles than FiVe1[1]. |
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体外研究
(In Vitro) | Vimentin-IN-1 (compound 4e) (0-10 mM; 72 h) inhibits a marked improvement in potency with an IC50value of 44 nM against HT-1080 fibrosarcoma, better than than FiVe1 (IC50=1.6 μM, HT-1080)[1].
Vimentin-IN-1 (0.1 μM; 24 h) induces phosphorylation of VIM at Ser56[1].
Vimentin-IN-1 (100 μM; sampled at 0, 5, 15, 30, 45, and 60 min) exhibits poor stability with 0.0% remaining after 60 min of incubation in mouse liver microsome[1].
Cell Viability Assay[1] | Cell Line: | HT-1080, RD, and MCF-7 cells | | Concentration: | 0-10 mM | | Incubation Time: | 72 hours | | Result: | Inhibited HT-1080, RD, and MCF-7 cells with IC50s of 44 nM, 61 nM, and 49 nM, respectively. |
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体内研究
(In Vivo) | Vimentin-IN-1 (compound 4e) (10 mg/kg; p.o.; single dose) shows better oral pharmacokinetic properties than Five1[1].
Pharmacokinetic properties of Vimentin-IN-1 in mice[1]
| Route | Dose (mg/kg) | AUC0-last(ng·h/mL) | AUC0-inf(ng·h/mL) | T1/2(h) | Tmax(h) | Tlast(h) | Cmax(ng/mL) | | 4e | PO | 10 | 371.33 | 534.33 | 4.68 | 0.67 | 8 | 154.67 | | 4e | IP | 1 | 208.33 | 211.33 | 0.59 | 0.25 | 4 | 197.00 | | Five1 | PO | 25 | 309.78 | 339.21 | 4.57 | 0.5 | 18 | 110.43 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : 25 mg/mL(64.22 mM;Need ultrasonic) 配制储备液 | 1 mM | 2.5688 mL | 12.8442 mL | 25.6885 mL | | 5 mM | 0.5138 mL | 2.5688 mL | 5.1377 mL | | 10 mM | 0.2569 mL | 1.2844 mL | 2.5688 mL |
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储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month。-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: 2.5 mg/mL (6.42 mM); Suspended solution; Need ultrasonic
此方案可获得 2.5 mg/mL (6.42 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 25.0 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。 *以上所有助溶剂都可在本网站选购。
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