PX-12 (PX12) (1-methylpropyl 2-imidazolyl disulfide) is a small-molecule inhibitor of Trx-1 (thioredoxin-1), stimulates apoptosis, down-regulates HIF-1α and vascular endothelial growth factor (VEGF) and inhibits tumor growth in animal models. Since high levels of Trx-1 have been associated with colorectal, gastric and lung cancers, PX-12 is indicated as a potential cancer treatment in combination with chemotherapy for patients with advanced metastatic cancer. Initial trials correlated doses of Px-12 with increased patient survival.

HT29 cells:2.9 μM, MCF-7 cells:1.9 μM

在MCF-7和HT-29细胞中，PX-12抑制低氧（1%氧气）诱导的HIF-1alpha蛋白增加，并减少HIF-1转录激活活性、VEGF形成和可诱导性一氧化氮合酶。PX-12还以1.9μM和2.9μM的IC50抑制MCF-7和HT-29细胞的生长。[1] PX-12通过Nrf2/PMF-1介导的增加还能抑制HIF-1α蛋白水平。[2] 在A549细胞中，PX-12通过G2/M期阻滞以及Bax介导和ROS依赖的凋亡抑制细胞生长。[3] 在肝癌细胞中，PX-12与5-FU协同作用明显抑制肿瘤形成。[4]

在携带MCF-7肿瘤异种移植的小鼠中，PX-12 (12 mg/kg, i.p.) 降低了HIF-1α和VEGF蛋白水平以及微血管密度。[1]

Cell growth is measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Cells are exposed to a range of concentrations of PX-12 or pleurotin for 16 h in air or hypoxia (1% oxygen). The cells are then washed with warm drug-free medium and grown in air for the remainder of the 72-h incubation.(Only for Reference)