The anticancer activity of a novel pure 1,4-Diaryl-2-azetidinone (1), endowed with a higher solubility than the well known Combretastatin A4, is tested in mice. We previously reported that Compound (1) showed specific antiproliferative activity against duodenal and colon cancer cells, inducing activation of AMP-activated protein kinase and apoptosis. Here we estimate that the maximum tolerated dose in a mouse model is 40 mg/kg; the drug is well tolerated both in single dose and in repeated administration schedules. The drug displays a significant antitumor activity and a tumor growth delay when administered at the MTD both in single and fractionated i.v. administration in a mouse xenograft model of colorectal cancer. Arrest of tumor growth and relapse after drug suspension are parallel to modification in glucose demand as shown by PET studies with [(18)F] FDG. These data strongly support Compound (1) as a promising molecule for in vivo treatment of colorectal cancer.