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MI-538
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
MI-538图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
1mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍
MI-538是menin和MLL融合蛋白相互作用的抑制剂;IC50值为21nM。

Cell experiment:

MOLM-13, MV4;11, HL-60 human leukemia cells as well as MLL-AF9 and HM-2 murine bone marrow cells are treated with MI-538 or 0.25% DMSO for 7 days. Media are changed at day 4 with viable cell number restored to the original concentration, and MI-538 are resupplied. An amount of 100 μL of cell suspension is transferred to 96-well plates for each sample in quadruplicates. Cell viability is measured using the MTT assay. Plates are read for absorbance at 570 nm[1].

Animal experiment:

Mice: Mice xenograft are randomly grouped with each group containing eight mice. Vehicle or MI-538 (45 mg/kg) are administrated once daily at designated doses using ip injections for 2 weeks. Body weight and tumor sizes are monitored three times a week[1].

产品描述

MI-538 is an inhibitor of the interaction between menin and MLL fusion proteins with an IC50 of 21 nM.

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[1].

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%)[1].

[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.