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- W128180301 abstract "Cyclin dependent kinases (Cdks) have been considered to be important targets in cancer therapeutics due to their critical involvement in cell cycle control. Recent genetic knockout studies in mice have indicated that there is a significant level of redundancy between the Cdks that regulate cell cycle progression. Therefore, an inhibitor that affects multiple Cdks would be more effective at inducing cell cycle arrests in a broad spectrum of cancers than an inhibitor that targets only one. This study involves the characterization of a novel series of small molecule inhibitors that target Cdks 1, 2, and 4. These inhibitors were identified by high throughput in silico molecular screening, targeted to a conserved structural site on Cdk2 that is distinct from the ATP binding site. The mechanism of action of these small molecules is the induced reduction of the apparent levels of Cdks 1, 2, and 4 in cells. This decrease in functional Cdk protein is associated with a decrease in Rb phosphorylation as well as E2F-dependent gene transcription. Multiple lines of evidence including immunofluorescence and ultracentrifugation indicate that the compounds directly induce Cdk1, Cdk2, and Cdk4 protein aggregation." @default.
- W128180301 created "2016-06-24" @default.
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- W128180301 date "2009-04-01" @default.
- W128180301 modified "2023-09-25" @default.
- W128180301 title "Novel Cdk inhibitors identified by in silico screening act through a novel mechanism" @default.
- W128180301 doi "https://doi.org/10.1096/fasebj.23.1_supplement.756.17" @default.
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