| 产品描述： | MI-538 is an inhibitor of the interaction between menin and MLL fusion proteins with an IC50 of 21 nM |
| 靶点： |
IC50 : 21 nM (menin and MLL interaction); Kd: 6.5 nM (menin);EpigeneticReaderDomain; HistoneMethyltransferase |
| 体外研究： |
MI-538 inhibits the proliferation of MLL leukemia cells with a GI50 of 83 nM. MI-538 shows no effect (up to 6 μM) on growth of the control cell lines HL-60 and HM-2, which do not harbor MLL translocations, demonstrating good selectivity toward MLL fusion protein transformed cells. MI-538 binds to menin with low nanomolar affinity (Kd=6.5 nM). Its potent cellular activity originates from the improved binding affinity to menin and possibly increased cell membrane permeability. Treatment with MI-538 results in strong down regulation of expression of Hoxa9 and Meis1 genes. About 100 nM 27 was sufficient to reduce by ~50% Hoxa9 expression in MLL-AF9 cells, and even more pronounced effect was seen on Meis1 expression |
| 体内研究： |
Treatment with MI-538 results in a pronounced, about 80%, reduction in the MV4;11 tumor volume, without causing substantial signs of toxicity reflected by less than 10% reduction of the body weight. MI-538 demonstrates markedly improved exposure (area under the curve, AUC, values), Cmax (maximum compound concentration) in the blood plasma, and the lowest value of clearance. The half-life of MI-538 is about 1.6 h. MI-538 has also high oral bioavailability (~50%) |
| 参考文献： |
1. Borkin D, et al. Property Focused Structure-Based Optimization of Small Molecule Inhibitors of the Protein-Protein Interaction between Menin and Mixed Lineage Leukemia (MLL). J Med Chem. 2016 Feb 11;59(3):892-913. |
| 溶解性： |
soluble in DMSO |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
1.765 ml |
8.825 ml |
17.649 ml |
| 5 mM |
0.353 ml |
1.765 ml |
3.53 ml |
| 10 mM |
0.176 ml |
0.882 ml |
1.765 ml |
| 50 mM |
0.035 ml |
0.176 ml |
0.353 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