TY - JOUR
T1 - Cdc7 kinase - A new target for drug development
AU - Swords, Ronan
AU - Mahalingam, Devalingam
AU - O'Dwyer, Michael
AU - Santocanale, Corrado
AU - Kelly, Kevin
AU - Carew, Jennifer
AU - Giles, Francis
PY - 2010/1
Y1 - 2010/1
N2 - 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.
AB - 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.
KW - Cdc7 kinase
KW - Cell cycle
KW - Drug development
KW - Target
UR - http://www.scopus.com/inward/record.url?scp=71049184413&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=71049184413&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2009.09.020
DO - 10.1016/j.ejca.2009.09.020
M3 - Article
C2 - 19815406
AN - SCOPUS:71049184413
SN - 0959-8049
VL - 46
SP - 33
EP - 40
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 1
ER -