| 名稱 | 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. |
| 細(xì)胞實(shí)驗(yàn) | 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]. |
| 動物實(shí)驗(yàn) | 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]. |
| 體外活性 | 方法: 六種惡性膠質(zhì)瘤細(xì)胞系 A-172、AM-38、T98G、U-138MG、U-251MG 和 YH-13 用 Lenalidomide (0.01-100 μM) 處理 72 h，使用 Coulter counter assay 檢測細(xì)胞數(shù)目。
結(jié)果: Lenalidomide 以濃度依賴的方式抑制所有惡性神經(jīng)膠質(zhì)瘤細(xì)胞的細(xì)胞計數(shù)。[1]
方法: DC 從 MM 患者的 BM CD14+ 細(xì)胞分化，用 Lenalidomide (0.1-1 μM) 處理 8 天，使用 flow-cytometry 分析 DC 成熟標(biāo)志物。
結(jié)果: 盡管成熟 DC 的數(shù)量和百分比都有所減少，但在 MM 患者體內(nèi)達(dá)到的濃度范圍內(nèi)，Lenalidomide 顯著增加了來源于 BM 的 DC 的 HLA-DR、CD86 和 CD209 ?的表達(dá)。[2] |
| 體內(nèi)活性 | 方法: 為檢測體內(nèi)抗腫瘤活性，將 Lenalidomide (25 mg/kg) 腹腔注射給攜帶 5TGM1 腫瘤的 C57BL/KaLwRij 或 B6-SCID 小鼠，每天一次，持續(xù) 21 天。
結(jié)果: Lenalidomide 抑制了攜帶 5TGM1 的 C57BL/KaLwRij 小鼠的腫瘤生長并延長了其生存期。Lenalidomide 顯著增加了 B6-SCID 小鼠模型中分泌 IFN-γ 的 CD4+ 和 CD8+ T 細(xì)胞的數(shù)量，但對 NK 細(xì)胞和 B 細(xì)胞沒有影響。Lenalidomide 在體內(nèi)略微降低了 CD25+Foxp3+ T 細(xì)胞的數(shù)量，但增加了 CD8+ T 細(xì)胞中穿孔素的表達(dá)。Lenalidomide 在體內(nèi)促進(jìn)了 1 型抗腫瘤免疫反應(yīng)。[3] |
| 存儲條件 | 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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| 關(guān)鍵字 | 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 |
| 相關(guān)產(chǎn)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 |
| 相關(guān)庫 | 經(jīng)典已知活性庫 | 已知活性化合物庫 | EMA 上市藥物庫 | 抗衰老化合物庫 | FDA 上市藥物庫 | 藥物功能重定位化合物庫 | 抗癌臨床化合物庫 | 抗癌藥物庫 |