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Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

5.5K
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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M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

6.2K
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...
6.2K
Positive Regulator Molecules02:39

Positive Regulator Molecules

6.4K
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.
6.4K
Positive Regulator Molecules01:45

Positive Regulator Molecules

133.8K
To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
133.8K
Anaphase Promoting Complex00:50

Anaphase Promoting Complex

3.3K
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...
3.3K
S-Cdk Initiates DNA Replication02:38

S-Cdk Initiates DNA Replication

5.3K
The cell cycle is a series of events leading to DNA duplication followed by the division of cell content to form two daughter cells. The cell cycle progresses in four stages—the cell increases in size (gap 1 or G1-phase), duplicates its DNA (synthesis or S-phase), prepares to divide (gap 2 or G2-phase), and divides (mitosis or M-phase).
Two states at the origin of replication
In eukaryotes, the initiation of replication occurs at many sites on the chromosomes, called the origins of...
5.3K

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Related Experiment Video

Updated: Jan 9, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

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

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Recent advance in macrocyclic CDK inhibitors.

Jiamin Zheng1, Zhisen Zhang1, Jinxin Liu2

  • 1Department of Medicinal Chemistry, Insilico Medicine Shanghai Ltd., Shanghai, China.

Future Medicinal Chemistry
|December 9, 2025
PubMed
Summary
This summary is machine-generated.

Macrocycles offer a promising strategy to develop novel cyclin-dependent kinase (CDK) inhibitors, potentially overcoming resistance and toxicity issues seen with current cancer therapies.

Keywords:
Drug designcyclin-dependent kinasesdrug discoverymacrocyclesoncological therapeutics

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Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

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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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Through the Looking Glass: Time-lapse Microscopy and Longitudinal Tracking of Single Cells to Study Anti-cancer Therapeutics
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Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
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Area of Science:

  • Medicinal Chemistry
  • Oncology
  • Molecular Biology

Background:

  • Cyclin-dependent kinases (CDKs) are crucial regulators of cell cycle and transcription, making them key targets in cancer therapy.
  • CDK4/6 inhibitors have shown success in breast cancer, but challenges like resistance and off-target toxicity persist.
  • Macrocycle-based drug design is emerging as a strategy to improve kinase inhibitor efficacy and drug-like properties.

Purpose of the Study:

  • To review recent advancements in macrocyclization strategies for developing cyclin-dependent kinase (CDK) inhibitors.
  • To highlight how macrocyclic scaffolds can address limitations of current CDK-targeted therapies.
  • To explore the structural evolution of CDK inhibitors from acyclic to macrocyclic forms.

Main Methods:

  • Literature review of scientific publications and clinical trials from 2015-2025.
  • Analysis of structural modifications in CDK inhibitor design, focusing on macrocyclization techniques.
  • Evaluation of the impact of macrocyclization on kinase inhibitory activity, selectivity, and drug-like properties.

Main Results:

  • Macrocyclization strategies have enhanced the potency and selectivity of CDK inhibitors.
  • Macrocyclic CDK inhibitors show potential in overcoming acquired resistance mechanisms.
  • Improved pharmacokinetic profiles and reduced off-target effects are observed with macrocyclic designs.

Conclusions:

  • Macrocyclization represents a powerful approach for designing next-generation CDK inhibitors.
  • These novel macrocyclic agents hold significant promise for improving cancer treatment outcomes.
  • Further research and clinical evaluation are warranted to fully realize the therapeutic potential of macrocyclic CDK inhibitors.