Drug design with Cdc7 kinase: a potential novel cancer therapy target

Abstract

Identifi cation of novel molecular targets is critical in development of new and effi cient cancer therapies. Kinases are one of the most common drug targets with a potential for cancer therapy. Cell cycle progression is regulated by a number of kinases, some of which are being developed to treat cancer. Cdc7 is a serine-threonine kinase originally discovered in budding yeast, which has been shown to be necessary to initiate the S phase. Inhibition of Cdc7 in cancer cells retards the progression of the S phase, accumulates DNA damage, and induces p53-independent cell death, but the same treatment in normal cells does not signifi cantly affect viability. Low-molecular-weight compounds that inhibit Cdc7 kinase with an IC 50 of less than 10 nM have been identifi ed, and shown to be effective in the inhibition of tumor growth in animal models. Thus Cdc7 kinase can be recognized as a novel molecular target for cancer therapy.