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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...

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...

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.

mTOR Signaling and Cancer Progression

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...

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Related Experiment Video

Updated: Jun 4, 2025

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

Quest for discovering novel CDK12 inhibitor.

Abhijit Debnath¹, Rajesh Kumar Singh², Rupa Mazumder¹

¹Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida, India.

Journal of Receptor and Signal Transduction Research

|December 19, 2024

Summary

Researchers identified a novel small molecule, ZINC11784547, as a potent inhibitor of Cyclin-Dependent Kinase 12 (CDK12). This compound shows promise for cancer therapy by effectively inhibiting cancer cell growth and promoting cell death.

Keywords:

CDK12 Consensus molecular docking Ewing sarcoma cancer prostate cancer

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Related Experiment Videos

Last Updated: Jun 4, 2025

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

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Identification of Novel CK2 Kinase Substrates Using a Versatile Biochemical Approach

Published on: February 21, 2019

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

Area of Science:

Oncology
Molecular Biology
Drug Discovery

Background:

Cyclin-Dependent Kinase 12 (CDK12) plays a crucial role in RNA processing, transcription, and cell cycle regulation.
CDK12 is implicated as an oncogenic factor in various cancers, including breast, thyroid, liver, prostate, and Ewing sarcoma, making it a significant biomarker and therapeutic target.
Small-molecule inhibitors are sought as affordable alternatives to monoclonal antibodies for CDK12-targeted cancer therapy.

Purpose of the Study:

To identify effective and affordable small-molecule inhibitors of CDK12 through high-throughput virtual screening.
To evaluate potential drug candidates for their binding affinity, pharmacokinetic properties, toxicity, and efficacy against cancer cells.

Main Methods:

Utilized the RASPD protocol for virtual screening of three databases against CDK12.
Conducted drug-likeness, molecular docking, ADME/toxicity predictions, consensus molecular docking, and MD simulations.
Performed in vitro studies, including MTT assays, to assess the cytotoxic effect of identified compounds.

Main Results:

Identified ZINC11784547 as a promising CDK12 inhibitor.
ZINC11784547 demonstrated robust binding affinity, favorable ADME properties, low toxicity, and remarkable stability.
The compound exhibited a significant cytotoxic effect, indicating its potential to induce cancer cell death.

Conclusions:

ZINC11784547 is a potent small-molecule inhibitor of CDK12 with favorable drug-like properties and demonstrated efficacy in preclinical assessments.
This compound represents a promising candidate for developing novel CDK12-targeted cancer therapies, offering a potentially more accessible treatment option.