Fenretinide (4-HPR) is an orally-active synthetic retinoid derivative with potential antineoplastic and chemopreventive activities.

Fenretinide在选定的T-ALL细胞系中展现出不仅是急性的，而且是长期的抗肿瘤活性。Fenretinide以剂量和时间依赖的方式抑制CCRF-CEM白血病细胞中的DES活性，导致内源性细胞内dhCer含量的同步增加。Fenretinide (3 μM)诱导的dhCer在CCRF-CEM和Jurkat细胞中积累[1]。使用Fenretinide抑制神经酰胺可保护胰岛素信号。Fenretinide阻止脂质引起的胰岛素刺激的葡萄糖摄取减少[2]。Fenretinide在高于1μM的浓度下抑制OVCAR-5细胞增殖和活力，10μM时可实现70-90%的生长抑制。1μM的Fenretinide在预培养3天后显著抑制OVCAR-5细胞侵袭。用1μM的4-HPR处理的内皮细胞不能形成管状结构，而是形成小的细胞聚集体[4]。

Fenretinide（10 mg/kg，i.p.）在高脂饮食喂养的雄性C57Bl/6小鼠中选择性抑制神经酰胺积累。Fenretinide治疗通过葡萄糖和胰岛素耐量测试，提高了葡萄糖耐受性和胰岛素敏感性[2]。将25 mg/kg的酮康唑添加至Fenretinide，可以增加NOD/SCID小鼠的4-HPR血浆水平[3]。

Fenretinide is dissolved in DMSO. Standard XTT assay is used to determine cell viability. For fenretinide-only treatments, cells are plated in 96-well plates at 750,000 cells/mL and 100 μL/well. After 4 h, treatments are added on 50 μL/well obtaining a final density of 500,000 cells/mL and final volume of 150 μL/well. Four replicates are used per experimental condition. XTT reagent mixture is added 4 h before the end of selected treatment period and absorbance at 490 nm is determined per each well. A slightly modified protocol is used for analysis of the effect of myriocin (final concentration of 100 nM) or antioxidant on Fenretinide treatment. Briefly, cells are seeded on 60 mm culture dishes and myriocin or antioxidants added after 4 h. Fenretinide treatment is added 2 h later and cells are plated in quadruplicates in 96 well plates (150 μL/well).