MPT0G211 是一种高效、口服活性和选择性的HDAC6抑制剂 (IC50=0.291 nM)。MPT0G211 对 HDAC6 的选择性是其他 HDAC 亚型的 1000 倍。MPT0G211 可以透过血脑屏障。MPT0G211 改善阿尔茨海默病模型中 tau 磷酸化和认知缺陷。MPT0G211 具有抗转移和神经保护作用。抗癌活性。
| 生物活性 | MPT0G211 is a potent, orally active and selectiveHDAC6inhibitor (IC50=0.291 nM). MPT0G211 displays >1000-fold selective forHDAC6over otherHDACisoforms. MPT0G211 can penetrate the blood-brain barrier. MPT0G211 ameliorates tau phosphorylation and cognitive deficits in an Alzheimer’s disease model. MPT0G211 has anti-metastatic and neuroprotective effects. Anticancer activities[1][2][3]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | MPT0G211 (0.1 μM; cells were transfected with pCAX APP 695 and pRK5-EGFP-Tau P301L for 24 h) significantly inhibits the phosphorylation of tau Ser396[1].
MPT0G211 inhibits HDAC6/Hsp90 binding and causes subsequent proteasomal degradation of polyubiquitinated proteins[1].
MPT0G211 significantly decreases the phosphorylation of tau by GSK3β inactivation[1].
MPT0G211 (0.1 μM; 24 hours) significantly attenuates the phosphorylation of tau Ser396 and Ser404 in both cell lines (SH-SY5Y and Neuro-2a cells were transfected for 24 h with pCAX APP 695 and pRK5-EGFP-Tau P301L)[1].
MPT0G211 inhibits MDA-MB-231 and MCF-7 cells growth (GI50=16.19 and 5.6 μM, respectively)[2].
In AML cells, MPT0G211 potentiated the cytotoxic effects of DOXO by impairing DNA repair machinery and activating Bcl-2-associated X protein (BCL-XL)-dependent cell apoptosis[3].
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体内研究
(In Vivo) | MPT0G211 (50 mg/kg; p.o.; daily for 3 months) significantly ameliorates the spatial memory impairment[1].
MPT0G211 (25 mg/kg; i.p. ; qd; day 73 post-tumor injection) reduces numbers of nodules and lung weights[2].
MPT0G211 treatment not only diminishes tau phosphorylation by inhibition GSK3β activity but also enhances the acetylation of Hsp90, which causes the downregulation of HDAC6/Hsp90 binding and facilitates proteasomal degradation of polyubiquitinated p-tau[1].
| Animal Model: | Triple transgenic (3×Tg-AD) mice (harboring APPSweand tauP301Lmutant transgenes[1] | | Dosage: | 50 mg/kg | | Administration: | P.o.; daily for 3 months | | Result: | Significantly ameliorated the spatial memory impairment. |
| Animal Model: | Female SCID mice (bearing MDA-MB-231 cells)[2] | | Dosage: | 25 mg/kg | | Administration: | I.p.; qd; day 73 post-tumor injection | | Result: | Significantly reduced numbers of nodules and lung weights. |
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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 : 100 mg/mL(340.92 mM;Need ultrasonic) 配制储备液 | 1 mM | 3.4092 mL | 17.0462 mL | 34.0925 mL | | 5 mM | 0.6818 mL | 3.4092 mL | 6.8185 mL | | 10 mM | 0.3409 mL | 1.7046 mL | 3.4092 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 90% (20%SBE-β-CDin saline) Solubility: ≥ 2.5 mg/mL (8.52 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (8.52 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 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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