Video Experimental Relacionado

Updated: Jan 14, 2026

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

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

Análisis de selectividad de inhibidores de CDK2 mediante dinámica molecular de CDK1 y CDK2

Dmitrii O Shkil¹, Anastasia S Fokina², Dariy T Asainov¹

¹Moscow Institute of Physics and Technology, Institutskiy per. 9, Dolgoprudny, 141701, Russia.

Journal of molecular graphics & modelling

|January 12, 2026

Abstract:

Cyclin-dependent kinases (CDKs) are pivotal regulators of the cell cycle and attractive therapeutic targets, particularly in breast cancer treatment. However, achieving selectivity among closely related CDKs, such as CDK2/CDK1, remains a significant challenge in drug discovery. In this study, we leverage molecular dynamics simulations and protein-ligand interaction analyses to uncover the structural and pharmacophoric determinants that drive selective inhibition of these kinases. By comparing known inhibitors and their contacts with CDK1 and CDK2, we identify critical pharmacophoric features essential for achieving target-specific selectivity. These findings provide valuable hypotheses into the design of next-generation CDK inhibitors with improved therapeutic profiles, addressing the pressing need for selective and effective cancer therapies.

Palabras clave:

CDK1 CDK2 Quinasa dependiente de ciclina Inhibidor de quinasa Dinámica molecular Selectividad

Más Videos Relacionados

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

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

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

Published on: February 25, 2016

Videos de Conceptos Relacionados

Inhibition of Cdk Activity

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 Molecules

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 Molecules

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 Mitosis

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...

S-Cdk Initiates DNA Replication

S-Cdk Initiates DNA Replication

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...

Anaphase Promoting Complex

Anaphase Promoting Complex

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...