FA16 是一种特异、代谢稳定的铁死亡 (ferroptosis) 诱导剂 (IC50=1.26 μM; HT1080 cells)，是 2-(三氟甲基) 苯并咪唑的衍生物。胱氨酸/谷氨酸反转运蛋白 (system Xc-) 介导了细胞内谷氨酸和细胞外胱氨酸的交换，FA16 通过抑制 system Xc-行使功能。FA16 也能够在 HepG2 异种移植瘤模型中显著抑制肿瘤生长。
| 生物活性 | FA16 is a specificferroptosisinducer (IC50=1.26 μM; HT1080 cells) with metabolic stability, is the derivate of 2-(trifluoromethyl)benzimidazole. FA16 acts by inhibiting cystine/glutamate antiporter (system Xc-), which mediates the exchange of intracellular glutamate and extracellular cystine. FA16 significantly inhibits tumor growth in the HepG2 xenograft model[1]. |
体外研究
(In Vitro) | FA16 (1 μM; 5 min) 在大鼠和人肝微粒体中具有满意的代谢稳定性[1]。
FA16 (5 μM; 10 h) 诱导 HT1080 细胞中脂质 ROS 积累并抑制谷氨酸释放[1]。
FA16 (5 μM; 24 h) 结果线粒体萎缩，膜密度增大，符合铁衰相关的形态特征[1]。
FA16 (10 μM; 24 h) 诱导的铁死亡能够被铁脱落抑制剂 Fer-1、Trolox 或 DFO 挽救，而凋亡或坏死抑制剂则对其无效[1]。
| Parameter | Microsomal stability (T1/2min) | Intrinsic clearance (μL/min/ mg protein) | | Human | 15.6 | 88.6 | | Rat | 10.4 | 132.8 |
Cell Viability Assay[1] | Cell Line: | Human cancer cell lines: Clear-cell renal cell carcinoma cells (786-O), breast cancer cells (MDA-MB-231), cervical cancer cells (HeLa), hepatocellular carcinoma cells (HepG2), melanoma cells (A375), and prostate cancer cells (DU145); Human normal cell lines: cardiomyocytes (AC16), colon mucosal epithelial cells (NCM460), embryonic kidney cells (293T), and hepatic cells (LO2) | | Concentration: | 0-10 μM | | Incubation Time: | 48 hours | | Result: | Inhibited cell growth with IC50s of 0.7 μM (786-O), 4.34 μM (MDA-MB-231), 1.91 μM (HeLa), 1.33 μM (HepG2), 2.31 μM (A375), and 1.64 μM (DU145), respectively. |
Immunofluorescence[1] | Cell Line: | HT1080 cells | | Concentration: | 5 μM | | Incubation Time: | 10 hours | | Result: | Significantly induced lipid ROS accumulation, as indicated by the great enhancement in green fluorescence intensity. |
RT-PCR[1] | Cell Line: | HT1080 cells | | Concentration: | 0.5 μM, 1 μM, and 5 μM | | Incubation Time: | 6 hours and 18 hours | | Result: | Increased the system Xc-component SLC7A11, ChaC GSHspecific γ-glutamylcyclotransferase 1 (CHAC1), but little changed GPX4. |
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体内研究
(In Vivo) | FA16 (15 或 30 mg/kg; 腹腔注射; 隔天给药, 共 21 天) 在 786-O 异种移植物小鼠模型中显著抑制肿瘤生长，安全性好 (不引起体重下降)，还诱导肿瘤组织中发生铁死亡[1]。
| Animal Model: | BALB/c nude mice bearing HepG2 tumors (s.c.)[1] | | Dosage: | 15 or 30 mg/kg | | Administration: | Intraperitoneal injection; every other for 21 days | | Result: | Significantly inhibited tumor growth with a tumor growth inhibition (TGI) value of 47.6% and 77.1% at 15 and 30 mg/ kg, respectively. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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