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Menin-MLL inhibitor MI-2

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Chemical Structure| 1271738-62-5 同义名 : MI-2;Menin-MLL Inhibitor;MI-2 MLL inhibitor;Menin-MLL inhibitor 2
CAS号 : 1271738-62-5
货号 : A166598
分子式 : C18H25N5S2
纯度 : 98%
分子量 : 375.555
MDL号 : MFCD22575021
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(133.14 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • Histone Methyltransferase

    Menin-MLL, IC50:446 nM
描述 MI-2 is a potent menin-MLL inhibitor with IC50 value of 446nM. Treatment with MI-2 at concentration of 12.5μM, 25μM and 50μM, efficiently disrupted the menin-MLL-AF9 complex without affecting the expression level of menin and MLL-AF9 in HEK293 cells transfected with Flag-MLL-AF9. It reduced menin-MLL-AF9 occupancy on the Hoxa9 locus and downregulated MLL fusion target genes. MI-2 blocked proliferation of MLL-AF9 and MLL-ENL transduced BMC, with GI50 value of about 5μM, but showed only a small effect on the cell growth of E2A-HLF transduced BMC. MI-2 substantially and specifically reduced the immortalization potential of cells transformed with MLL fusion oncoproteins. Treatment with MI-2 and MI-3 resulted in much smaller, diffuse colonies, indicative of differentiation[3]. MI-2 also works as a direct inhibitor of the lanosterol synthase. It induced prominent accumulation of 24,25 epoxycholesterol and Shunt pathway metabolites[4].
作用机制 MI-2 can disrupt the menin-MLL-AF9 complex and reduce menin-MLL-AF9 occupancy on the Hoxa9 locus, thus downregulating MLL fusion target genes.[3]
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT01528696 Obesity Compl... 展开 >>ications; Caesarean Section, Wound 收起 << Phase 4 Terminated(Insufficient Recrui... 展开 >>tment) 收起 << - United States, Michigan ... 展开 >> University of Michigan Von Voigtlander Womens' Hospital Ann Arbor, Michigan, United States, 48109 收起 <<
NCT01528696 - Terminated(Insufficient Recrui... 展开 >>tment) 收起 << - -
NCT03680391 - Not yet recruiting October 2019 Egypt ... 展开 >> Kasr Alainy medical school Cairo, Egypt, 12111 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.66mL

0.53mL

0.27mL

13.31mL

2.66mL

1.33mL

26.63mL

5.33mL

2.66mL
参考文献

[1]Grembecka J, He S, et al. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol. 2012 Jan 29;8(3):277-84.

[2]Phillips RE, Yang Y, et al. Target identification reveals lanosterol synthase as a vulnerability in glioma. Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7957-7962.

[3]Grembecka J, He S, Shi A, Purohit T, Muntean AG, Sorenson RJ, Showalter HD, Murai MJ, Belcher AM, Hartley T, Hess JL, Cierpicki T. Menin-MLL inhibitors reverse oncogenic activity of MLL fusion proteins in leukemia. Nat Chem Biol. 2012 Jan 29;8(3):277-84. doi: 10.1038/nchembio.773. PMID: 22286128; PMCID: PMC3401603.

[4]Phillips RE, Yang Y, Smith RC, Thompson BM, Yamasaki T, Soto-Feliciano YM, Funato K, Liang Y, Garcia-Bermudez J, Wang X, Garcia BA, Yamasaki K, McDonald JG, Birsoy K, Tabar V, Allis CD. Target identification reveals lanosterol synthase as a vulnerability in glioma. Proc Natl Acad Sci U S A. 2019 Apr 16;116(16):7957-7962. doi: 10.1073/pnas.1820989116. Epub 2019 Mar 28. PMID: 30923116; PMCID: PMC6475387.