One of the first anti-angiogenic molecules proposed was TNP-470 (AGM-1470), an analog of fumagillin, a naturally secreted antibiotic of the fungus Aspergillus fumigatus fresenius (Ingber et al. 1990), identified by its ability to inhibit endothelial proliferation in vitro. Subsequently, its TNP-470 analog was shown to inhibit tumor growth in multiple xenograft models (Ingber et al. 1990; Kurebayashi et al. 1994; Kusaka et al. 1991; Yamaoka et al. 1993a,b). Based on these experiments, TNP-470 aroused much interest as a potential anti-angiogenic agent; however, testing in preclinical models of neuroblastoma has demonstrated relatively modest anti-tumor effects (Katzenstein et al. 1999; Nagabuchi et al. 1997; Shusterman et al. 2001). Some investigators indicate that TNP-470 is most effective when small neuroblastoma tumors are treated (Katzenstein et al. 1999; Shusterman et al. 2001), suggesting that this agent may be more effective in the setting of minimal residual disease.

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