1. ¹Sbarro Institute for Cancer Research and Molecular Medicine, Centre of Biotechnology, Temple University, Philadelphia, PA, USA
2. ²Department of Biomedical Sciences, Division of Biochemistry, University of Sassari, Sassari, Italy
3. ³Department of Human Pathology and Oncology, University of Siena, Siena, Italy
4. ⁴Laboratory 'C', Department for the Development of Therapeutic Programs, Center for Experimental Research, Regina Elena Cancer Institute, Rome, Italy
5. ⁵Department of Medicine and Public Health, Section of Clinical Anatomy, Second University of Naples, Naples, Italy

Correspondence: Dr A Giordano, Sbarro Institute for Cancer Research and Molecular Medicine, Centre of Biotechnology, Temple University, Bio Life Science Building, Suite 333, 1900 N 12th Street, Philadelphia, PA 19122, USA. E-mail: giordano@temple.edu

Received 19 January 2005; Accepted 10 March 2005; Published online 16 October 2006.

Abstract

One strategy in the development of anticancer therapeutics has been to arrest malignant proliferation through inhibition of the enzymatic activity of cyclin-dependent kinases (cdks), which are key regulatory molecules of the cell cycle. Over the past few years, numerous compounds with remarkable cdk inhibitory activity have been studied in cancer therapy, although it is very difficult to point out the best cdk to target. An excellent candidate appears to be cdk2, whose alteration is a pathogenic hallmark of tumorigenesis. The small molecule described in our study showed an inhibitory effect on the kinase activity of cdk2, a significant growth arrest observed in a colony formation assay and a reduction in the size of the tumor in nude mice, thus suggesting its potential role as a promising new type of mechanism-based antitumor drug, also for the treatment of hyperproliferative disorders.