Related Experiment Video

Updated: Sep 7, 2025

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
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Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

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Targeting cyclin-dependent kinase 1 (CDK1) in cancer: molecular docking and dynamic simulations of potential CDK1

Shazia Sofi1, Umar Mehraj1, Hina Qayoom1

  • 1Department of Bioresources, School of Biological Sciences, University of Kashmir, Srinagar, J&K, 190006, India.

Medical Oncology (Northwood, London, England)
|June 20, 2022
PubMed

Insights

Targeting cyclin-dependent kinase 1 (CDK1) may combat cancer. New dinaciclib analogs show high affinity and stability, offering potential therapeutic replacements for CDK1 inhibition in cancer treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cell cycle dysregulation drives cancer through uncontrolled proliferation.
  • Cyclin-dependent kinase 1 (CDK1) is crucial for cell cycle maintenance and often overexpressed in malignancies.
  • CDK1 inhibitors present a potential therapeutic strategy for restoring cell cycle control in cancer.

Purpose of the Study:

  • To identify and classify inhibitors with high affinity for CDK1.
  • To evaluate the expression pattern and prognostic significance of CDK1 in various cancers.
  • To discover novel CDK1 inhibitors structurally similar to dinaciclib with improved therapeutic potential.

Main Methods:

  • Drug likeness analysis of dinaciclib analogs.
  • Molecular docking and simulation to assess binding affinity and stability.
  • Analysis of CDK1 expression and its correlation with patient survival (Overall Survival and Relapse-Free Survival).

Main Results:

  • CDK1 is significantly upregulated across multiple cancer types, correlating with poorer patient survival.
  • Two novel dinaciclib analogs demonstrated potent CDK1 inhibition with superior binding affinity and stability compared to dinaciclib.
  • The identified analogs possess favorable ADMET properties, suggesting therapeutic viability.

Conclusions:

  • Elevated CDK1 expression is a marker of poor prognosis in cancer.
  • Novel dinaciclib analogs are promising candidates for CDK1-targeted cancer therapy.
  • These findings support further preclinical and clinical research for dinaciclib analogs in cancer treatment and prevention.
Keywords:
Breast cancerCDK1Cell cycleDinaciclibMolecular dynamic simulation

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