| 产品描述： | 组蛋白甲基转移酶抑制剂;Histone Methyltransferase Inhibitors;;InformationMI-463 MI-463 is a potent inhibitor of Menin-MLL interaction with an IC50 value of 15.3 nM.TargetsMenin-MLL interaction (Cell-free assay) 15.3 nMIn vitroMI-463 demonstrates profound on-target activity in MLL leukemia cells. MI-463 results in substantial growth inhibition, with half-maximal growth inhibitory concentration (GI50) values of 0.23 μM, measured after 7 days of treatment in MLL leukemia cells. MI-463 is effective in inducing differentiation of MLL leukemia cells. Treatment with sub-micromolar concentrations of MI-463 also leads to markedly reduced expression of Hoxa9 and Meis1, downstream targets of MLL fusion proteins substantially upregulated in MLL leukemias.In vivoMI-463 shows substantial survival benefit in mouse models of MLL leukemia. It has very favorable druglike properties, including metabolic stability and PK profile in mice. MI-463 achieves high levels in peripheral blood following a single intravenous or oral dose, while also showing high oral bioavailability(∼45%). In a mouse xenograft model using MV4;11 human MLL leukemia cells implanted into BALB/c nude mice, MI-463 induces strong inhibition of tumor growth with once-daily intraperitoneal (i.p.) administration. It does not impair normal hematopoiesis in vivo.Cell Research(from reference)Cell lines：leukemia cells Incubation Time：6 or 7 days |
| 体内研究： |
MI-463 在单次静脉内或口服剂量后在外周血中达到高水平，同时还显示出高口服生物利用度 (45%)。menin-MLL 相互作用的药理学抑制通过靶向活性显著延迟了小鼠模型中 MLL 白血病的进展而不会引起毒性。每天一次腹膜内 (ip) 给药后，MI-463 会强烈抑制肿瘤生长。MLL 融合蛋白靶基因 HOXA9 和 MEIS1 的表达在用 MI-463 处理后显著降低。用 MI-463 处理 MV4；11 异种移植受体小鼠 20 天也导致白血病进展显著延迟，表现为生物发光水平显著降低，这与外周血中白血病细胞群的显著减少有关，脾脏和骨髓样本。 |
| 参考文献： |
1. Borkin D, et al. Pharmacologic inhibition of the Menin-MLL interaction blocks progression of MLL leukemia in vivo. Cancer Cell. 2015 Apr 13;27(4):589-602. |
| 保存条件： |
-80℃（运输条件：冰袋低温运输） |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.064 ml |
10.319 ml |
20.638 ml |
| 5 mM |
0.413 ml |
2.064 ml |
4.128 ml |
| 10 mM |
0.206 ml |
1.032 ml |
2.064 ml |
| 50 mM |
0.041 ml |
0.206 ml |
0.413 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京