Abstract Purpose: KML001 (sodium metaarsenite) is an orally available arsenic compound that has entered phase II clinical trials in solid tumors. The aim of this study is to assess vascular-disrupting properties of KML001 and to investigate whether KML001 as VDA (vascular-disrupting agent) augments anti-tumor effects of irinotecan in a murine model of colon cancer. Experimental Design: Female BALBc mice bearing subcutaneos CT26 colon carcinoma cells were injected intraperitoneally with KML001(10 mg/kg) or irinotecan alone, or coadministered weekly for 4 weeks. Moreover, we assessed cytoskeletal changes of HUVEC cells when treated with KML001. Results: We observed massive necrosis in the central part of the tumor by 24 h after treated with KML001 alone and the regrowth was seen from the periphery of the tumor after 2 days. Otherwise, we observed the significant tumor growth delay when KML001 was administered either 24 hr or 72hr after irinotecan. In addition, we found that KML001 degraded tubulin in HUVEC cells, which might be related with vascular disrupting properties of KML001. Evidence of proteosome-mediated degradation was obtained by demonstrating that adding a proteosome inhibitor. Conclusions: These results suggest that KML001 is a novel VDA, which can increase anti-tumor activities of irinotecan. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2595. doi:10.1158/1538-7445.AM2011-2595