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Druggable cavities and allosteric modulators of the cell division cycle 7 (CDC7) kinase

Authors :
Elisa Rojas-Prats
Loreto Martinez-Gonzalez
Carmen Gil
David Ramírez
Ana Martinez
Source :
Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 39, Iss 1 (2024)
Publication Year :
2024
Publisher :
Taylor & Francis Group, 2024.

Abstract

AbstractCell division cycle 7 kinase (CDC7) has been found overexpressed in many cancer cell lines being also one of the kinases involved in the nuclear protein TDP-43 phosphorylation in vivo. Thus, inhibitors of CDC7 are emerging drug candidates for the treatment of oncological and neurodegenerative unmet diseases. All the known CDC7 inhibitors are ATP-competitives, lacking of selectivity enough for success in clinical trials. As allosteric sites are less conserved among kinase proteins, discovery of allosteric modulators of CDC7 is a great challenge and opportunity in this field.Using different computational approaches, we have here identified new druggable cavities on the human CDC7 structure and subsequently selective CDC7 inhibitors with allosteric modulation mainly targeting the pockets where the interaction between this kinase and its activator DBF4 takes place.

Details

Language :
English
ISSN :
14756366 and 14756374
Volume :
39
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal of Enzyme Inhibition and Medicinal Chemistry
Publication Type :
Academic Journal
Accession number :
edsdoj.9474a61b420473c8be3cc0a61492459
Document Type :
article
Full Text :
https://doi.org/10.1080/14756366.2024.2301767