生物活性

• 靶点	Thymidine Phosphorylase IC50:0.62μM

• 描述In tumors, doxifluridine is converted to 5-FU by thymidine phosphorylase (TP). TP, also known asplatelet-derived endothelial cell growth factor, is upregulated in many solid tumors including breast, prostate and colorectal cancers. Elevated levels of TP are associated with tumor aggressionand poor prognosis. Doxifluridine, a derivative of 5-fluorouracil (5-FU) with less severe systemic toxicity, is a TP activator and widely used to treat various cancers. Doxifluridine significantly inhibited tube formation compared with the untreated control group (P< 0.0001). Doxifluridine at 10 μM significantly suppressed VEGF (vascular endothelial growth factor) expression in FU-MMT-1 cells compared with the control group in vitro (P< 0.01). Low-dose doxifluridine (1 μM) slightly increased TSP-1 expression (P = 0.272) in HUVEC, whereas high-dose doxifluridine (100 μM) reduced TSP-1 expression. Low-dose doxifluridine (1 and 10 μM) significantly increased TSP-1 expression in FU-MMT-1 cells compared with the control group (1 μM, P = 0.041; 10 μM, P = 0.0089). Further, doxifluridine (100 μM) reduced the proliferation of HUVEC compared with the control group. Administration of doxifluridine in combination with TNP-470 showed significantly greater suppression of tumor growth compared with either treatment alone. Following treatment, the tumor completely disappeared in five of six (83.3%) mice treated with the MTD (maximum tolerated dose) of doxifluridine in combination with TNP-470^[1].