DMU2139

The cytochrome P450 (CYP) enzyme superfamily plays a key role in the phase 1 oxidative metabolism and detoxification of both endogenous and xenobiotic substances. CYP1B1, belonging to the CYP1 subfamily, has been identified as a key enzyme in the carcinogenic action of 17-β-estradiol (E₂) and participates by catalysing hydroxylation at C-4 in E₂ to generate 4-hydroxyestradiol (4-OHE₂). MU2139 is a potent and specific inhibitor of CYP1B1 with IC₅₀ of 9 nM. MU2139 shows 88 and 133-fold selectivity over CYP1A1 and CYP1A2. IC₅₀ for MU2139 in live yeast cells was determined to be 65 nM. This result indicates MU2139 can enter live yeast cells to inhibit the endoplasmic reticular membrane-bound CYP1B1. IC₅₀ value for MU2139 was found to be in the range of 4-53 nM in live human HEK293 cells. This result indicates that MU2139 potently inhibits the human CYP1B1 enzyme that resides on the endoplasmic reticular membranes within human cells. In the presence of DMU2139, the EC₅₀ is reversed back to 8.3 μM from 61 μM indicating that DMU2139 overcomes cisplatin resistance in adherent HEK293 cells that overexpress CYP1B1¹.

溶解方案(细胞实验)

DMSO 中的溶解度 : 77.5 mg/mL (267.86 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)|Ethanol 中的溶解度 : 5 mg/mL (17.28 mM; 超声助溶)

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: ≥ 2.58 mg/mL (8.92 mM); 澄清溶液 此方案可获得 ≥ 2.58 mg/mL（饱和度未知）的澄清溶液。以 1 mL 工作液为例，取 100 μL 25.8 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% Corn OilSolubility: ≥ 2.58 mg/mL (8.92 mM); 澄清溶液 此方案可获得 ≥ 2.58 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 25.8 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。"