| 名称 | Lenalidomide |
| 描述 | Lenalidomide (CC-5013) is an immunomodulator with oral activity. Lenalidomide is a ligand for the ubiquitin E3 ligase cereblon (CRBN), which selectively ubiquitinates and degrades two lymphoid transcription factors, IKZF1 and IKZF3, via the CRBN-CRL4 ubiquitin ligase, and is commonly used in the synthesis of PROTAC products. |
| 细胞实验 | The human NSCLC cell lines Lu-99, H1299, A549, EBC1, and H460 were cultured in RPMI-1640 medium containing 10% fetal bovine serum and antibiotics at 37°C in a humidified chamber containing 5% CO2. Cells were seeded into 60-mm culture dishes (2x10^5 cells per dish) with various concentrations of lenalidomide and incubated for various times [1]. |
| 动物实验 | Mice were administered sterile preparations of lenalidomide normalized to body weight. Intravenously (IV) dosed animals received drug by bolus tail vein injections, and extravascularly dosed mice received drug by bolus intraperitoneal injections (IP) or oral gavage (PO). Dosing solution, concentrations were adjusted so dose volumes ranged between approximately 100 and 150 μL for IV injections and between approximately 150 and 250 μL for IP and PO dosing in the pharmacokinetic study. However, for the range-finding study, increased dose volumes were used (up to 200 μL IV, 300 μL IP, and 600 μL PO, per approved animal use protocol) to explore elevated lenalidomide doses. The bolus injection rates for all IV, IP, or PO injections were less than 5 s. Concentrations of dosing solutions were verified by liquid chromatography-mass spectrometry [4]. |
| 体外活性 | 方法: 六种恶性胶质瘤细胞系 A-172、AM-38、T98G、U-138MG、U-251MG 和 YH-13 用 Lenalidomide (0.01-100 µM) 处理 72 h，使用 Coulter counter assay 检测细胞数目。
结果: Lenalidomide 以浓度依赖的方式抑制所有恶性神经胶质瘤细胞的细胞计数。[1]
方法: DC 从 MM 患者的 BM CD14+ 细胞分化，用 Lenalidomide (0.1-1 µM) 处理 8 天，使用 flow-cytometry 分析 DC 成熟标志物。
结果: 尽管成熟 DC 的数量和百分比都有所减少，但在 MM 患者体内达到的浓度范围内，Lenalidomide 显著增加了来源于 BM 的 DC 的 HLA-DR、CD86 和 CD209 的表达。[2] |
| 体内活性 | 方法: 为检测体内抗肿瘤活性，将 Lenalidomide (25 mg/kg) 腹腔注射给携带 5TGM1 肿瘤的 C57BL/KaLwRij 或 B6-SCID 小鼠，每天一次，持续 21 天。
结果: Lenalidomide 抑制了携带 5TGM1 的 C57BL/KaLwRij 小鼠的肿瘤生长并延长了其生存期。Lenalidomide 显著增加了 B6-SCID 小鼠模型中分泌 IFN-γ 的 CD4+ 和 CD8+ T 细胞的数量，但对 NK 细胞和 B 细胞没有影响。Lenalidomide 在体内略微降低了 CD25+Foxp3+ T 细胞的数量，但增加了 CD8+ T 细胞中穿孔素的表达。Lenalidomide 在体内促进了 1 型抗肿瘤免疫反应。[3] |
| 存储条件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | DMSO : 50 mg/mL (192.86 mM)
10% DMSO+90% Saline : 2.59 mg/mL (9.99 mM), Please add co-solvents sequentially, clarifying the solution as much as possible before adding the next one. Dissolve by heating and/or sonication if necessary. Working solution is recommended to be prepared and used immediately.
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| 关键字 | myeloma | Inhibitor | CRL4 | ligase | IKZF1 | Ligands for E3 Ligase | E3 ligase-recruiting Moiety | Apoptosis | immunomodulatory | cereblon | analog | multiple | CC5013 | inhibit | ligand | Lenalidomide | CC 5013 | IKZF3 | Molecular Glues | degradation |
| 相关产品 | L-Glutamic acid | Metronidazole | 5-Fluorouracil | Dextran sulfate sodium salt (MW 4500-5500) | Stavudine | Tributyrin | Myricetin | Sorafenib | L-Ascorbic acid | Acetylcysteine | Salicylic acid | Sodium 4-phenylbutyrate |
| 相关库 | 经典已知活性库 | 已知活性化合物库 | EMA 上市药物库 | 抗衰老化合物库 | FDA 上市药物库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |