Structures of small-molecule vascular disrupting agents. (A) Natural products and combretastatin-inspired molecular structures found to be effective tubulin binding agents causing vascular disruption. Combretastatin A4 [15], AVE8062 [155], combretastatin A1P [14], ZD6126 [156], BNC105P [157], CKD-516 [158], OXi8007 [17], colchicine, KGP18 [144], OXi6916 [159] and SCB01A [160]. (B) Diverse molecular structures binding tubulin or causing vascular disruption: ABT-751 [143], EPC2407 [131], DMXAA [138], arsenic trioxide [161], paclitaxel [162], TZT-1027 [163], NPI-235 [124], MN-029 [39] and CYT997 [34]. While paclitaxel is a tubulin binding agent, we found no evidence for acute vascular shutdown (see Figure 6e).