Identification of effective cyclin-dependent kinase 3/cyclin E inhibitors using multi-level computational screening
Srutishree Sarma1, Dikshita Dowerah2, Shilpa Neog1
1CMML-Catalysis and Molecular Modelling Lab, Department of Chemical Sciences, Tezpur University, Napaam, 784028, Sonitpur, Assam, India.
Computers in Biology and Medicine
|October 9, 2025
Summary
Researchers identified CID_25211747 as a potent inhibitor of Cyclin-dependent kinase 3 (CDK3), a key target in cancer therapy. This discovery offers a promising new direction for developing effective CDK3 antagonists and future cancer treatments.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Cyclin-dependent kinase 3 (CDK3) regulates cell cycle progression.
- CDK3 is overexpressed in various cancers, presenting a therapeutic target.
- Currently, no specific CDK3 inhibitors are available.
Purpose of the Study:
- To identify effective inhibitors of CDK3/cyclin E.
- To screen a library of 204 CDK3 inhibitor derivatives computationally.
- To nominate a lead compound for CDK3 antagonist development.
Main Methods:
- Utilized a multi-tiered computational pipeline including molecular docking.
- Performed ADMET profiling, global reactivity studies, and molecular dynamics (MD) simulations.
- Employed N-layered Integrated molecular Orbital and molecular Mechanics (ONIOM) calculations for binding affinity analysis.
Main Results:
- Identified interactions between top candidates and crucial CDK3 residues.
- MD simulations and ONIOM calculations confirmed stable ligand-receptor interactions and favorable binding energetics.
- Extended simulations highlighted the exceptional stability and strong binding affinity of CID_25211747.
Conclusions:
- CID_25211747 demonstrated optimal inhibition and stability against CDK3.
- The compound shows promise as a lead for developing novel CDK3 antagonists.
- Provides valuable insights for future anticancer drug design targeting CDK3.
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