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Discovery of novel furanone derivatives as potent Cdc7 kinase inhibitors.
- Source :
-
European journal of medicinal chemistry [Eur J Med Chem] 2017 Apr 21; Vol. 130, pp. 406-418. Date of Electronic Publication: 2017 Feb 17. - Publication Year :
- 2017
-
Abstract
- Cdc7 is a serine-threonine kinase and plays a conserved and important role in DNA replication, and it has been recognized as a potential anticancer target. Herein, we report the design, synthesis and structure-activity relationship of novel furanone derivatives as Cdc7 kinase inhibitors. Compound 13 was identified as a strong inhibitor of Cdc7 with an IC <subscript>50</subscript> value of 0.6 nM in the presence of 1 mM ATP and showed excellent kinase selectivity. In addition, it exhibited slow off-rate characteristics, which may offer advantages over known Cdc7 inhibitors in its potential to yield prolonged inhibitory effects in vivo. Compound 13 potently inhibited Cdc7 activity in cancer cells, and effectively induced cell death.<br /> (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Subjects :
- Cell Cycle Proteins drug effects
Cell Death drug effects
Cell Line, Tumor
Drug Discovery
Humans
Protein Kinase Inhibitors chemistry
Protein Kinase Inhibitors pharmacology
Structure-Activity Relationship
Cell Cycle Proteins antagonists & inhibitors
Furans pharmacology
Protein Serine-Threonine Kinases antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1768-3254
- Volume :
- 130
- Database :
- MEDLINE
- Journal :
- European journal of medicinal chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 28279847
- Full Text :
- https://doi.org/10.1016/j.ejmech.2017.02.030