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Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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Positive Regulator Molecules02:39

Positive Regulator Molecules

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Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
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M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

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Checkpoints throughout the cell cycle serve as safeguards and gatekeepers, allowing the cell cycle to progress in favorable conditions and slow or halt it in problematic ones. This regulation is known as the cell cycle control system.
Cyclin-dependent kinases, or Cdks, work in concert with cyclins to control cell cycle transitions. M-Cdk, a complex of Cdk1 bound to M cyclin, is a well-known example of this coordinated control that drives the transition from the G2 to the M phase.
M cyclin...
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Anaphase Promoting Complex00:50

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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Negative Regulator Molecules01:23

Negative Regulator Molecules

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Positive regulators allow a cell to advance through cell cycle checkpoints. Negative regulators have an equally important role as they terminate a cell’s progression through the cell cycle—or pause it—until the cell meets specific criteria.
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Targeted Cancer Therapies02:57

Targeted Cancer Therapies

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The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
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Related Experiment Video

Updated: Aug 1, 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 Protein-Protein Interactions to Inhibit Cyclin-Dependent Kinases.

Mark Klein1,2

  • 1Hematology/Oncology Section, Primary Care Service Line, Minneapolis VA Healthcare System, Minneapolis, MN 55417, USA.

Pharmaceuticals (Basel, Switzerland)
|April 28, 2023
PubMed
Summary

Targeting protein-protein interactions (PPI) of cyclin-dependent kinases (CDKs) offers a path to selective cancer drugs. Research shows promising molecules, laying groundwork for future CDK-targeted therapies.

Keywords:
cyclincyclin-dependent kinaseneoplasmprotein-protein interaction inhibitor

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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

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Last Updated: Aug 1, 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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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations
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Studying Proteolysis of Cyclin B at the Single Cell Level in Whole Cell Populations

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Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cyclin-dependent kinases (CDKs) are crucial in cell regulation and cancer.
  • CDK4 inhibitors are approved for breast cancer, driving interest in targeting other CDKs.
  • Developing selective CDK inhibitors is challenging due to conserved ATP-binding sites.

Purpose of the Study:

  • To review literature on targeting protein-protein interactions (PPI) involving CDKs 2, 4, 5, and 9.
  • To explore PPI targeting as a strategy for achieving greater drug selectivity.
  • To identify promising lead molecules for CDK-targeted therapies.

Main Methods:

  • Literature review focused on studies targeting CDK-involving PPI.
  • Analysis of challenges and opportunities in targeting these interactions.
  • Identification and summary of promising lead compounds.

Main Results:

  • Promising lead molecules targeting specific CDKs have been identified through PPI inhibition strategies.
  • Protein-protein interactions offer a less conserved target compared to ATP-binding sites, aiding selectivity.
  • No lead molecules have yet achieved FDA approval.

Conclusions:

  • Targeting CDK-mediated PPI is a viable strategy for developing selective anti-cancer drugs.
  • The reviewed studies provide a foundation for future development of PPI inhibitors for CDKs.
  • Further research is needed to advance lead molecules to clinical application.