MI-136

MI-136 can selectively inhibit the interaction of menin and MLL. It also suppresses DHT-induced expression of androgen receptor (AR) target genes.

MI-136 can disrupt menin-MLL interaction. MI-136 inhibits AR-mediated transcription by blocking MLL recruitment predominantly at the level of the menin-MLL interaction. In the presence of MI-136, the recruitment of ASH2L (but not AR) to TMPRSS2 and PSA promoters was significantly decreased, thus inhibiting the expression of genes that were bound to ASH2L after AR stimulation. AR positive cell lines such as VCaP, LNCaP and 22RV1 were sensitive to MI-136. It blocked DHT-induced cell proliferation in AR-dependent cell lines (LNCaP and VCaP) and induced apoptosis of VCaP cells as evidenced by PARP cleavage. Treatment of VCaP tumor-bearing mice with MI-136 (40mg/kg) led to a modest but significant reduction in tumor volume².

溶解方案(细胞实验)

DMSO 中的溶解度 : 110 mg/mL (233.79 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: ≥ 2.75 mg/mL (5.84 mM); 澄清溶液 此方案可获得 ≥ 2.75 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 27.5 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: ≥ 2.75 mg/mL (5.84 mM); 澄清溶液 此方案可获得 ≥ 2.75 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 27.5 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: ≥ 2.75 mg/mL (5.84 mM); 澄清溶液 此方案可获得 ≥ 2.75 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 27.5 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"