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Volume 21, Issue 15
  • ISSN: 1570-1808
  • E-ISSN: 1875-628X

Abstract

Background

CDK4/6 plays a crucial role in regulating cell proliferation, and inhibiting this kinase can effectively prevent the initiation of cell growth and division. However, current FDA-approved CDK4/6 inhibitors have limitations such as poor bioavailability, adverse effects, high cost, and limited accessibility. Thus, this research aimed to discover novel CDK4/6 inhibitors to overcome the challenges associated with FDA-approved inhibitors.

Methods

To identify potential CDK4/6 inhibitors, we have performed structure-based virtual screening. Chem-space and Mcule databases have been screened, followed by a series of filtering steps. These steps included assessing drug-likeness, PAINS alert, synthetic accessibility scores, ADMET properties, consensus molecular docking, and performing molecular dynamics simulations.

Results

Four new compounds (CSC089414133, CSC091186116, CSC096023304, CSC101755872) have been identified as potential CDK4/6 inhibitors. These compounds exhibited strong binding affinity with CDK4/6, possessed drug-like features, showed no PAINS alert, had a low synthetic accessibility score, demonstrated effective ADMET properties, were non-toxic, and exhibited high stability.

Conclusion

Inhibiting CDK4/6 with the identified compounds may lead to reduced cell proliferation and the promotion of cancer cell death.

© 2024 Bentham Science Publishers
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2024-12-29

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Identification of Novel CDK 4/6 Inhibitors by High-throughput Virtual Screening
Letters in Drug Design & Discovery 21, 3229 (2024); https://doi.org/10.2174/0115701808273043231130100833
/content/journals/lddd/10.2174/0115701808273043231130100833
/content/journals/lddd/10.2174/0115701808273043231130100833
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  • Article Type:     Research Article
Keyword(s): Breast cancer; cancer drug discovery; cancer drugs; CDK4/6; CDK4/6 inhibitors; cyclin-dependent kinase; cyclin-dependent kinase inhibitor; kinase; kinase inhibitor

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