| 名称 | Bemcentinib |
| 描述 | Bemcentinib (R428) belongs to small molecule inhibitors and is a highly selective oral Axl inhibitor (IC50 = 14 nM) with oral bioavailability and potent cell permeability. This compound effectively inhibits cancer cell migration and invasion, blocks tumor dissemination, and prolongs survival in various tumor models. |
| 细胞实验 | MDA-MB-231 or 4T1 cells (1 × 10^5) were allowed to migrate through Matrigel toward 20% FCS in an 8-μm pore 24-well Transwell plate at 37°C for 16 to 24 h. Noninvaded cells and Matrigel were removed by swabbing. Invaded cells were fixed in 4% formaldehyde, stained with 1% crystal violet, and quantified as for Axl cell-based assay. Cells were preincubated with R428 for 3 h. R428 was added to both upper and lower Transwell chambers [1]. |
| 激酶实验 | A five-point R428 dose titration was performed in radiometric in vitro kinase assays on 133 kinases at the Km(ATP) for each kinase. Axl, Mer, and Tyro3 assays were also performed using a fluorescence polarization protocol. HER2 activity was determined by Z'-LYTE assay [1]. |
| 动物实验 | Female BALB/c mice were inoculated in the mammary fat pad with 0.5 × 10^6 4T1 cells. Forty-eight hours after inoculation, mice were randomized into treatment groups (n = 10). Oral dosing with R428 (7–75 mg/kg twice daily) or vehicle continued until days 19 to 21. Cisplatin (1.2 or 4 mg/kg) was administered i.v. once weekly. Body weight and tumor size were measured thrice per week. Lungs were exposed postmortem. Total number and size of surface lung macrometastases were measured (small, <2 mm; medium, ≥2 mm and <3 mm; large, ≥3 mm). Half of each primary tumor was snap frozen in liquid nitrogen. The other half, and the livers were fixed in paraformaldehyde/lysine/periodate solution, paraffin embedded and sectioned (5 μm thick). Two H&E-stained liver sections per animal were examined microscopically for micrometastases in three view fields. Synergism was determined using Clark's synergy calculation [1]. |
| 体外活性 | 方法：在HCC827亲本及厄洛替尼耐药ER3、ER10细胞中，Bemcentinib（0.1–2.0 μM）处理120小时，采用IncuCyte实时生长曲线测定。
结果：Bemcentinib呈剂量依赖性抑制细胞增殖，诱导耐药细胞生长停滞。[1]
方法：在SET-2和BaF3-EpoR-JAK2V617F细胞中，Bemcentinib（0.5–5 μM）处理48小时；处理24小时（SET-2）或12小时（BaF3）。
结果：处理48小时，WST-1法检测显示其呈剂量依赖性抑制细胞活力；BrdU掺入及Annexin V染色证实其抑制细胞增殖并诱导凋亡。[2]
方法：在LX2人肝星状细胞中，Bemcentinib（0.25 μM）预处理1小时后加GAS6刺激；在原代小鼠Kupffer细胞中，Bemcentinib（0.25 μM）预处理后加LPS刺激2小时。
结果：ELISA检测显示其抑制MCP-1释放及p-AKT水平；RT-qPCR证实其降低IL-1β和IL-6 mRNA表达。[3] |
| 体内活性 | 方法：在HCC827细胞异种移植裸鼠模型中，Bemcentinib（50或100 mg/kg，每日两次，口服灌胃）联合厄洛替尼（50 mg/kg，每日一次）治疗138天。
结果：联合治疗显著延迟肿瘤耐药出现，至实验终点时肿瘤仍维持最大抑制效应。[1]
方法：在SET-2细胞异种移植NSG小鼠模型中，Bemcentinib（50 mg/kg，每日两次，口服灌胃）治疗至肿瘤达1500 mm³，肿瘤生长抑制60%。
结果：在BaF3-EpoR-JAK2V617F全身性模型中，Bemcentinib（50 mg/kg，每日两次）显著延长生存期，减轻脾肿大，并改善贫血。[2]
方法：在C57BL/6小鼠MCD或HFD诱导的NASH模型中，Bemcentinib（50 mg/kg，每日两次，口服灌胃）于饮食诱导最后2周给药。
结果：Bemcentinib显著减少肝脏胶原沉积（羟脯氨酸及天狼星红染色证实），并降低促炎及促纤维化基因表达。[3] |
| 存储条件 | Store at low temperature
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
Shipping with blue ice/Shipping at ambient temperature. |
| 溶解度 | H2O : < 1 mg/mL (insoluble or slightly soluble)
10% DMSO+40% PEG300+5% Tween-80+45% Saline : 1 mg/mL (1.97 mM), Sonication is recommended.
Ethanol : < 1 mg/mL (insoluble or slightly soluble)
DMSO : 23.4 mg/mL (46.19 mM), Sonication and heating are recommended.
10% DMSO+90% Saline : 1.1 mg/mL (2.17 mM), Suspension.
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| 关键字 | Tyro3 | TAMReceptor | TAM Receptor | R-428 | R 428 | Mer | Inhibitor | inhibit | BGB-324 | BGB 324 | Bemcentinib | AXL |
| 相关产品 | Cabozantinib S-malate | Tepotinib | Dubermatinib | Gilteritinib | AXL-IN-13 | NCT-503 | BMS 777607 | Sitravatinib | UNC 1062 | Cabozantinib | c-Fms-IN-3 | UNC2025 |
| 相关库 | 抑制剂库 | 抗癌活性化合物库 | 激酶抑制剂库 | 经典生物活性库 | 高选择性抑制剂库 | 生物活性化合物库 | 抗病毒库 | 膜蛋白靶向化合物库 | 酪氨酸激酶分子库 | 药物功能重定位化合物库 | 抗癌临床化合物库 | 抗癌药物库 |