Journal
FUTURE MEDICINAL CHEMISTRY
Volume 13, Issue 16, Pages 1317-1339Publisher
Newlands Press Ltd
DOI: 10.4155/fmc-2020-0393
Keywords
abemaciclib; CDK4; CoMFA; CoMSIA; MD simulation; 3D-QSAR
Categories
Funding
- National Natural Science Foundation of China [81872744]
- Shandong Provincial Natural Science Foundation [ZR2019MH046]
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The study focused on exploring the structure-activity relationship of CDK4 inhibitor analogs and designing potent CDK4 inhibitors for breast cancer therapy. By establishing a 3D quantitative structure-activity relationship model and conducting molecular dynamics simulation studies, valuable insights were gained for developing novel CDK4 inhibitors. Four novel inhibitors with satisfactory predicted binding affinity to CDK4 were successfully designed based on the findings.
Aim: CDK4 is a promising target for breast cancer therapy. This study aimed to explore the structure-activity relationship of CDK4 inhibitor abemaciclib analogs and design potent CDK4 inhibitors for breast cancer treatment. Methods & results: A faithful 3D quantitative structure-activity relationship model was established by molecular docking, comparative molecular field analysis and comparative molecular similarity index analysis based on 56 abemaciclib analogs. Molecular dynamics simulation studies revealed the key residues of the interaction between CDK4 and inhibitors. Four novel inhibitors with satisfactory predicted binding affinity to CDK4 were designed. Conclusion: The 3D quantitative structure-activity relationship and molecular dynamics simulation studies provide valuable insight into the development of novel CDK4 inhibitors.
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