ABT-751 (E7010) hydrochloride is a novel sulfonyl anti-mitotic compound and a tubulin binder with high oral bioavailability. This agent binds to the colchicine site on β-tubulin, inhibiting the polymerization of tubulin which results in cell cycle arrest at the G2/M phase and induces apoptosis, effectively preventing cell division. Additionally, ABT-751 (E7010) hydrochloride induces autophagy by inhibiting the AKT/MTOR signaling pathway. It exhibits significant inhibitory effects against various types of cancer cells, including lung, stomach, colon, and breast cancer.

ABT-751 hydrochloride (2 μM; 4, 8, 24h) 在 Hep-3B 细胞中施展多重作用: 破坏有丝分裂,降低线粒体膜电位,增加ROS生成及导致DNA损伤.此外,该化合物能抑制细胞增殖,诱导G2/M细胞周期的阻滞,及通过AKT/MTOR信号通路抑制来促进缺失TP53的Hep-3B细胞的自噬.ABT-751 hydrochloride也能通过caspase依赖性的外源性和内源性途径诱导细胞的凋亡.外源性表达TP53基因可增强ABT-751诱导的自噬与凋亡效应.

ABT-751 hydrochloride (100 mg/kg/day, 口服, 5 days on, 5 days off x2, 21天) 在治疗神经母细胞瘤时显示了优异的抑制效果,并在横纹肌肉瘤及肾母细胞瘤模型中有效减小或消退肿瘤体积.此外,ABT-751 在与 Vincristine 及 Paclitaxel 联用时表现出协同增效作用.同样,在小鼠的前列腺癌、非小细胞肺癌和乳腺癌异种移植模型中,ABT-751 hydrochloride (100 mg/kg/day, 口服, 5 days on, 5 days off x2) 与 Docetaxel 联合使用时也显著增强了对肿瘤的抑制效果.