PU 23 是一种非羧基多药耐药蛋白 4 (MRP4) 抑制剂，作为降低抗癌剂 6-Mercaptopurine 耐药性的活性剂。
PU 23 is a Multidrug resistance protein 4 (MRP4/ABCC4) inhibitor. MRP4 is an ATP-binding cassette (ABC) transporter. It is associated with multidrug resistance (MDR), which is becoming a growing challenge to the treatment of cancer and infections[1].
Then compound?PU 23?was discovered to improve HEK293/MRP4 cell sensibility to 6-MP dramatically, and low concentration?PU 23?(5 μM) achieved the equivalent effect of 50 μM MK571. The accumulation of 6-MP was determined by validated high-performance liquid chromatography methods, and pretreatment of the HEK293/MRP4 cells with 50 μM MK571 or?PU 23?resulted in significantly increased accumulation of 6-MP by approximately 1.5 times. This compound was first reported with a novel scaffold compared with previously known MRP4 inhibitors, which is a hopeful molecular tool that can be used for overcoming multidrug resistance research[2].
参考文献:
[1]: Chen Y, Yuan X, et al. Discovery of novel multidrug resistance protein 4 (MRP4) inhibitors as active agents reducing resistance to anticancer drug 6-Mercaptopurine (6-MP) by structure and ligand-based virtual screening. PLoS One. 2018 Oct 15;13(10):e0205175.?
PU 23 是一种多药耐药蛋白 4 (MRP4/ABCC4) 抑制剂。 MRP4 是一种 ATP 结合盒 (ABC) 转运蛋白。它与多药耐药性 (MDR) 相关，这正成为癌症和感染治疗面临的越来越大的挑战[1]。
随后发现化合物 PU 23 可显着提高 HEK293/MRP4 细胞对 6-MP 的敏感性，低浓度 PU 23 (5 μM) 达到与 50 μM MK571 相当的效果。 6-MP 的积累是通过经过验证的高效液相色谱法确定的，用 50 μM MK571 或 PU 23 预处理 HEK293/MRP4 细胞导致 6-MP 的积累显着增加约 1.5 倍。与先前已知的 MRP4 抑制剂相比，该化合物首次被报道具有新型支架，是一种有望用于克服多药耐药性研究的分子工具[2]。
| Cell experiment [1]: | |
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Cell lines |
HEK293/MRP4 cell line |
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Preparation Method |
MRP4 was overexpressed in the HEK293/MRP4 cell line. The PU 23 compounds in the presence of 6-MP(15 μM), using MK571 as the positive control.?Cell viability was assessed using sulforhodamine B (SRB) |
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Reaction Conditions |
10 μM PU 23 for 72h. |
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Applications |
PU 23?showed the highest activity with an inhibition rate of 81.71% at the concentration of 10 μM with 6-MP and only 15.26% without 6-MP.?It increased cell sensitivity to 6-MP, but not toxic on its own. |
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参考文献: [1]. Chen Y, Yuan X, et al. Discovery of novel multidrug resistance protein 4 (MRP4) inhibitors as active agents reducing resistance to anticancer drug 6-Mercaptopurine (6-MP) by structure and ligand-based virtual screening. PLoS One. 2018 Oct 15;13(10):e0205175.? |
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