DMU2139
目录号 : GC19416
DMU2139是一种有效的CYP1B1抑制剂，IC50值为9nM。
Cas No.:1821143-80-9
Sample solution is provided at 25 µL, 10mM.
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DMU2139 is a potent CYP1B1 inhibitor, with an IC50 value of 9nM[1]. DMU2139 coordinates with heme and interacts with the hydrophobic residues Phe134 and Phe231 through p-p stacking since the hydrophobic naphthyl group[2]. DMU2139 has been used in combination with cisplatin to overcome the resistance mediated by CYP1B1 and make cancer cells re-sensitized to cisplatin[3].
In vivo, the combination treatment of DMU2139 (30mg/kg) and olaparib (50mg/kg), administered by intraperitoneal injection every 4 days for 24 days, significantly inhibited tumor growth in a xenograft mouse model of A2780 cells[4].
References:
[1] Horley N J, Beresford K J M, Chawla T, et al. Discovery and characterization of novel CYP1B1 inhibitors based on heterocyclic chalcones: Overcoming cisplatin resistance in CYP1B1-overexpressing lines[J]. European journal of medicinal chemistry, 2017, 129: 159-174.
[2] Raju B, Choudhary S, Narendra G, et al. Molecular modeling approaches to address drug-metabolizing enzymes (DMEs) mediated chemoresistance: a review[J]. Drug Metabolism Reviews, 2021, 53(1): 45-75.
[3] Alsubait A, Aldossary W, Rashid M, et al. CYP1B1 gene: Implications in glaucoma and cancer[J]. Journal of cancer, 2020, 11(16): 4652.
[4] Xue Y, Yin T, Yuan S, et al. CYP1B1 promotes PARPi-resistance via histone H1. 4 interaction and increased chromatin accessibility in ovarian cancer[J]. Drug Resistance Updates, 2024, 77: 101151.
DMU2139是一种有效的CYP1B1抑制剂，IC50值为9nM[1]。由于疏水性萘基的存在，DMU2139可与血红素配位，并通过π-π堆积与疏水性残基Phe134和Phe231相互作用[2]。DMU2139已与顺铂联合使用，以克服CYP1B1介导的耐药性，使癌细胞重新对顺铂敏感[3]。
在体内，通过腹腔注射，每4天给药一次，持续24天，联合使用DMU2139（30mg/kg）和奥拉帕利（50mg/kg），在A2780细胞的异种移植小鼠模型中显著抑制了肿瘤生长[4]。
| Cell experiment [1]: | |
Cell lines | HEK293 cells |
Preparation Method | The recombinant HEK293 cells expressing CYP enzymes (1×105 cells/well) were seeded in a black 96-well transparent-bottom plate with a volume of 50μl. DMU2139 was added to the wells at different concentrations (1, 2, 4, 8, 10, 20, 40, 60, 80, and 100nM) and incubated at 37°C with 8% CO2 for 30 minutes. After incubation, 5μM of the fluorescent substrate 7-ethoxythioflavinol was added to each well, 25μl per well, and the mixture was shaken before the determination of 7-ethoxythioflavinol-O-demethylase (EROD) activity. Fluorescence detection was performed using the appropriate emission wavelength (530/30nm) and excitation wavelength (590/40nm). |
Reaction Conditions | 1, 2, 4, 8, 10, 20, 40, 60, 80, and 100nM; 30min |
Applications | DMU2139 treatment inhibited the CYP1B1 activity in HEK293 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Balb/c nude mice |
Preparation Method | Balb/c nude mice were raised under standard conditions and had free access to food and water. A2780 cells in the logarithmic growth phase were prepared at a concentration of 1×108 cells/ml, and 100µl of the cell suspension was subcutaneously injected into the axilla of each nude mouse. From the second day after injection, the tumor size was measured. When the average tumor volume reached approximately 100mm3, olaparib was administered intraperitoneally at a dose of 50mg/kg every 4 days, or in combination with DMU2139 (30mg/kg; i.p.) for 24 days. Measurements were taken using a vernier caliper every four days, and the formula for calculating tumor volume was: Volume (mm3) = (length×width2)/2. |
Dosage form | 30mg/kg; every 4 days for 24 days; i.p. |
Applications | DMU2139 treatment in combination with olaparib significantly inhibited the growth of A2780 cell-xenograft tumors in mice. |
References: | |
| Cas No. | 1821143-80-9 | SDF | |
| Canonical SMILES | O=C(C1=CC=C2C=C(OC)C=CC2=C1)/C=C/C3=CC=CN=C3 | ||
| 分子式 | C19H15NO2 | 分子量 | 289.33 |
| 溶解度 | Soluble in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.4563 mL | 17.2813 mL | 34.5626 mL |
| 5 mM | 691.3 μL | 3.4563 mL | 6.9125 mL |
| 10 mM | 345.6 μL | 1.7281 mL | 3.4563 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet