Menin-MLL inhibitor MI-2

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 differentiation³. MI-2 also works as a direct inhibitor of the lanosterol synthase. It induced prominent accumulation of 24,25 epoxycholesterol and Shunt pathway metabolites⁴.

溶解方案(细胞实验)

DMSO 中的溶解度 : 50 mg/mL (133.14 mM; 超声助溶; 吸湿的 DMSO 对产品的溶解度有显著影响，请使用新开封的 DMSO)

溶解方案(动物实验)

"方案 一": "请依序添加每种溶剂：10% DMSO 40% PEG300 5% Tween-80 45% SalineSolubility: ≥ 2.5 mg/mL (6.66 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；再向上述体系中加入 50 μL Tween-80，混合均匀；然后再继续加入 450 μL 生理盐水 定容至 1 mL。生理盐水的配制：将 0.9 g 氯化钠，溶解于 ddH₂O 并定容至 100 mL，可以得到澄清透明的生理盐水溶液。"

"方案 二": "请依序添加每种溶剂：10% DMSO 90% (20% SBE-β-CD in Saline)Solubility: ≥ 2.5 mg/mL (6.66 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液 中，混合均匀。2 g SBE-β-CD（磺丁基醚 β-环糊精）粉末定容于 10 mL 的生理盐水中，完全溶解至澄清透明。"

"方案 三": "请依序添加每种溶剂：10% DMSO 90% Corn OilSolubility: ≥ 2.5 mg/mL (6.66 mM); 澄清溶液 此方案可获得 ≥ 2.5 mg/mL（饱和度未知）的澄清溶液，此方案实验周期在半个月以上的动物实验酌情使用。以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"