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Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

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...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

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...
Positive Regulator Molecules02:39

Positive Regulator Molecules

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.
Positive Regulator Molecules01:45

Positive Regulator Molecules

To consistently produce healthy cells, the cell cycle—the process that generates daughter cells—must be precisely regulated.
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

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...
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

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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Related Experiment Video

Updated: Jun 24, 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

Published on: October 26, 2015

Selective CDK2 Degradation via Noncanonical Recruitment.

Yuanyuan Pei1,2, Weiye Lin3,2, Xinzhu Li2,4

  • 1School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Journal of Medicinal Chemistry
|June 23, 2026
PubMed
Summary

New molecular glues, B10 and B12, selectively degrade Cyclin-dependent kinase 2 (CDK2) by a unique mechanism. This discovery offers a promising strategy for targeting CDK2-driven cancers, with B12 showing strong in vivo efficacy.

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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
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Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

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Last Updated: Jun 24, 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

Published on: October 26, 2015

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay

Published on: May 3, 2018

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1
13:15

Experimental Approaches to Study Mitochondrial Localization and Function of a Nuclear Cell Cycle Kinase, Cdk1

Published on: February 25, 2016

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Discovery

Background:

  • Cyclin-dependent kinase 2 (CDK2) is a key therapeutic target in cancers resistant to CDK4/6 inhibitors or with CCNE1 amplification.
  • Selective CDK2 inhibition is challenging due to high structural homology among CDK family members.

Purpose of the Study:

  • To identify and characterize novel molecular degraders that selectively target CDK2.
  • To elucidate the structural and mechanistic basis for selective CDK2 degradation.

Main Methods:

  • Identification of cereblon (CRBN)-based molecular glue degraders (B10 and B12).
  • Determination of ternary complex structures between CRBN, CDK2, and the degraders.
  • Assessment of mechanistic effects on cell cycle progression and in vivo pharmacokinetics and target engagement.

Main Results:

  • B10 and B12 were identified as selective CDK2 degraders.
  • A noncanonical recruitment mode involving CDK2 Glu57 was revealed, stabilized by an extended CRBN-CDK2 interface.
  • Degraders induced G1/S-phase arrest by inhibiting retinoblastoma (Rb) phosphorylation and suppressed CDK2-dependent proliferation.
  • B12 demonstrated favorable pharmacokinetics, oral bioavailability, and in vivo intratumoral CDK2 degradation.

Conclusions:

  • The study provides a structural basis for designing selective kinase degraders.
  • B12 is established as a chemically tractable probe for targeting CDK2-driven malignancies.