Cdc7 kinase - A new target for drug development

Ronan Swords, Devalingam Mahalingam, Michael O'Dwyer, Corrado Santocanale, Kevin Kelly, Jennifer Carew, Francis Giles

Research output: Contribution to journalArticle

51 Scopus citations

Abstract

The cell division cycle 7 (Cdc7) is a serine threonine kinase that is of critical importance in the regulation of normal cell cycle progression. Cdc7 kinase is highly conserved during evolution and much has been learned about its biological roles in humans through the study of lower eukaryotes, particularly yeasts. Two important regulator proteins, Dbf4 and Drf1, bind to and modulate the kinase activity of human Cdc7 which phosphorylates several sites on Mcm2 (minichromosome maintenance protein 2), one of the six subunits of the replicative DNA helicase needed for duplication of the genome. Through regulation of both DNA synthesis and DNA damage response, both key functions in the survival of tumour cells, Cdc7 becomes an attractive target for pharmacological inhibition. There are much data available on the pre-clinical anti-cancer effects of Cdc7 depletion and although there are no available Cdc7 inhibitors in clinical trials as yet, several lead compounds are being optimised for this purpose. In this review, we will address the current status of Cdc7 as an important target for new drug development.

Original languageEnglish (US)
Pages (from-to)33-40
Number of pages8
JournalEuropean Journal of Cancer
Volume46
Issue number1
DOIs
StatePublished - Jan 1 2010

Keywords

  • Cdc7 kinase
  • Cell cycle
  • Drug development
  • Target

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Swords, R., Mahalingam, D., O'Dwyer, M., Santocanale, C., Kelly, K., Carew, J., & Giles, F. (2010). Cdc7 kinase - A new target for drug development. European Journal of Cancer, 46(1), 33-40. https://doi.org/10.1016/j.ejca.2009.09.020