MI-136
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
IC50:31 nM。
MI-136是menin-MLL相互作用抑制剂。
调节混合型白血病基因(MLL)的染色体易位可导致急性白血病产生治疗抗性。据报道,MLL融合蛋白的白血病活性取决于其与menin的相互作用,提供治疗干预的基础。
体外:研究发现,亚微摩尔浓度的MI-136能够强烈结合menin,Kd为24 nM,能够强效抑制menin与MLL的相互作用,并阻断MLL白血病细胞的增殖(在MLL-AF9细胞中GI50=0.55 μM),这表明MI-136代表menin-MLL抑制剂有价值的药效基团。另外,当在一组激酶和GPCR上进行分析时,MI-136未显示出实质的脱靶活性[1]。
体内:动物研究显示,与载体治疗对小鼠体重没有影响相比,用40 mg/kg的MI-136治疗带有VCaP肿瘤的小鼠导致肿瘤体积中度但显著的减少。这些数据表明,menin-MLL相互作用的药物抑制是对MLL白血病一种有效的体内治疗,并提供先进的分子骨架用于临床先导物鉴别[2]。
临床试验:到目前为止,MI-136仍处于临床前研究阶段。
参考文献:
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 Chemistry59(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).
Physical Appearance | A crystalline solid |
Storage | Store at -20°C |
M.Wt | 470.51 |
Cas No. | 1628316-74-4 |
Formula | C23H21F3N6S |
Solubility | Soluble in DMSO |
Chemical Name | 5-((4-((6-(2,2,2-trifluoroethyl)thieno[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)methyl)-1H-indole-2-carbonitrile |
SDF | Download SDF |
Canonical SMILES | N#CC(N1)=CC2=C1C=CC(CN3CCC(NC4=C(C=C(CC(F)(F)F)S5)C5=NC=N4)CC3)=C2 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存,请尽快用完。 |