Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

6.0K
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...
6.0K
M-Cdk Drives Transition Into Mitosis02:15

M-Cdk Drives Transition Into Mitosis

6.6K
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...
6.6K
Positive Regulator Molecules02:39

Positive Regulator Molecules

6.9K
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.
6.9K
Drug-Receptor Bonds01:25

Drug-Receptor Bonds

4.8K
Drug-receptor bonds are formed through various chemical forces when drugs interact with target cells. Covalent bonds, strong and irreversible, are exemplified by DNA-alkylating anticancer agents that inhibit cell division. However, such irreversible drug binding lacks selectivity and can modify the DNA of the surrounding healthy cells. Covalent binding often contributes to tissue toxicity, as seen with chloroform and paracetamol metabolites binding to the liver, causing hepatotoxicity.
In...
4.8K
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

1.8K
Drug design is a dynamic field that involves discovering and developing new medications based on specific biological targets. This process heavily relies on structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) to guide the design and optimization of efficient drugs.
SAR studies the intricate relationship between a drug's chemical structure and biological activity. It focuses on understanding how modifications to a drug's structure can influence...
1.8K
Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

6.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
6.7K

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Dual activation of MC3R and MC4R drives weight loss and reduces food intake in male primates with obesity.

Nature communications·2026
Same author

A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.

Nature communications·2026
Same author

The melanocortin receptors as targets for general obesity: contextualizing clinical failures and analyzing future perspectives.

Frontiers in endocrinology·2026
Same author

Evaluating Pediatric Emergency Care Within Epic Cosmos.

Pediatric emergency care·2026
Same author

Artificial Intelligence and Machine Learning in Health Care: Current Capabilities, Emerging Potential, and Future Directions.

The Medical clinics of North America·2026
Same author

Optimization and Chemoproteomic Profiling of a Selective, Covalent Bfl-1-Targeting Cellular Tool.

Journal of medicinal chemistry·2025
Same journal

Investigating the Inhibitory Properties of Diazo and Pyrazole-Carboxamide-Linked Benzenesulfonamides Against Carbonic Anhydrase Isoforms I, II, IX, and XII.

ChemMedChem·2026
Same journal

Quinoxaline-Based Monoamine Oxidase Inhibitors: Design Strategies, Synthesis, Structure-Activity Relationships, and Therapeutic Potential in Neurological Disorders: A Review From 1996 to 2026.

ChemMedChem·2026
Same journal

Immunomodulatory Potential of Quinoline Q3, a Selective Inhibitor of the Canonical NF-κB Pathway in Macrophages.

ChemMedChem·2026
Same journal

Synthesis and Biological Evaluation of C6-O-Glycosylated α-Mangostin Derivatives Against Methicillin-Resistant Staphylococcus aureus With Enhanced Bacterial Membrane Selectivity.

ChemMedChem·2026
Same journal

Piperazine Derivatives Carrying an Imidazole Ring as Selective Modulators of Human Carbonic Anhydrase Isozymes.

ChemMedChem·2026
Same journal

Discovery of Ligands for the TNFR1 Extracellular Domain Using Fragment-Based Drug Discovery.

ChemMedChem·2026
See all related articles

Related Experiment Video

Updated: Feb 16, 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

11.9K

Structure-Based Design of Selective Noncovalent CDK12 Inhibitors.

Jeffrey W Johannes1, Christopher R Denz1, Nancy Su2

  • 1Oncology, IMED Biotech Unit, AstraZeneca, Boston, MA, USA.

Chemmedchem
|December 22, 2017
PubMed
Summary
This summary is machine-generated.

Researchers developed selective small molecule inhibitors of Cyclin-dependent kinase (CDK) 12. These compounds decrease DNA-damage-response gene transcription and show toxicity to cancer cells, offering potential for new cancer therapies.

Keywords:
CDKkinasesoncologyselectivitytranscription

More Related Videos

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.6K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K

Related Experiment Videos

Last Updated: Feb 16, 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

11.9K
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

17.6K
Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
08:49

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries

Published on: January 22, 2019

9.6K

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Oncology

Background:

  • Cyclin-dependent kinase (CDK) 12 regulates DNA-damage-response genes.
  • CDK12 inhibition sensitizes BRCA wild-type cells to PARP inhibitors.
  • Development of small molecule CDK12 inhibitors is needed to mimic siRNA effects.

Purpose of the Study:

  • To design and synthesize potent and selective small molecule inhibitors of CDK12.
  • To evaluate the efficacy and selectivity of novel CDK12 inhibitors.

Main Methods:

  • Structure-based drug design and hybridization of existing compounds.
  • Chemical synthesis and optimization of lead compounds.
  • Kinase activity profiling, including selectivity panels and proteomics.

Main Results:

  • A series of selective CDK12 inhibitors were developed, including compound 7.
  • Compounds demonstrated selectivity against a broad kinase panel.
  • Inhibition of RNA polymerase II Ser2 phosphorylation confirmed CDK12 activity.
  • Selective compounds exhibited acute toxicity to OV90 and THP1 cells.

Conclusions:

  • Novel small molecules selectively inhibit CDK12.
  • These inhibitors reduce DNA-damage-response gene transcription.
  • The developed compounds show potential as anti-cancer agents, particularly in combination therapies.