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MI-136
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-136图片
CAS NO:1628316-74-4
包装与价格：
包装价格(元)
5mg电议
25mg电议

产品介绍
MI-136 是一种 menin-MLL 蛋白-蛋白相互作用 (PPI) 抑制剂，IC50 为 31 nM，Kd 为 23.6 nM。 MI-136 显示可阻断 AR 信号传导，并有可能用于去势抵抗性肿瘤的研究。
Cas No.1628316-74-4
化学名5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile
Canonical SMILESN#CC(N1)=CC2=C1C=CC(CN3CCC(NC4=C(C=C(CC(F)(F)F)S5)C5=NC=N4)CC3)=C2
分子式C23H21F3N6S
分子量470.51
溶解度DMF: 1 mg/ml,DMSO: 1 mg/ml,Ethanol: 10 mg/ml
储存条件Store at -20℃
General tipsFor obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.
Shipping ConditionEvaluation sample solution : ship with blue ice
All other available size: ship with RT , or blue ice upon request
产品描述

IC50: 31 nM

MI-136 is a menin-MLL interaction inhibitor.

Chromosomal translocations regulating mixed lineage leukemia gene (MLL) can result in the acute leukemias resistant to therapy. The leukemogenic activity of MLL fusion protein is reported to be dependent on its interactions with menin, providing the basis for therapeutic intervention.

In vitro: MI-136 was found to be able to strongly bind to menin with Kd of 24 nM, potently inhibit menin interaction with MLL, and block proliferation of MLL leukemia cells at submicromolar concentrations (GI50 = 0.55 μM in the MLL-AF9 cells), indicating that MI-136 represented a valuable pharmacophore for menin-MLL inhibitors. In addition, MI-136 did not show substantial off-target activity when profiled on a panel of kinases and GPCRs [1].

In vivo: Animal study showed that treatment of VCaP tumor–bearing mice with MI-136 at 40 mg/kg resulted in a modest but significant reduction in tumor volume when compared to vehicle treatment with no effect on body weight of mouse. These data demonstrated that the pharmacologic inhibition of the menin-MLL interaction was an effective in vivo treatment for MLL leukemias and provided advanced molecular scaffold for clinical lead identification [2].

Clinical trial: Up to now, MI-136 is still in the preclinical development stage.

References:
1. D. Borkin, J. Pollock, K. Kempinska,et al.Property focused structure-based optimization of small molecule inhibitors of the protein-protein interaction between menin and mixed lineage leukemia (MLL). Journal of Medicinal Chemistry 59(3),892-913(2016).
2. R. Malik, A. P. Khan, I. A. Asangani,et al. Targeting the MLL complex in castration-resistant prostate cancer.Nat. Med.21(4),344-352(2015).