Related Experiment Video

Updated: Sep 18, 2025

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

9.2K

Dual CDK6 and CDK9 inhibitors as anti-psoriasis agents: Design, synthesis, and anti-inflammatory activity

Yiming Ru1, Fang Zhao1, Haojie Zuo1

  • 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei 230012, China.

Bioorganic & Medicinal Chemistry Letters
|June 23, 2025
PubMed

Insights

Researchers developed dual CDK6 and CDK9 inhibitors to treat psoriasis. Compound 4 showed significant anti-inflammatory effects in vitro by inhibiting key pathways, offering a promising new therapeutic strategy for psoriasis.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Dermatology

Background:

  • Psoriasis is characterized by skin hyperplasia and inflammatory factor secretion.
  • CDK6 and CDK9 play cooperative roles in psoriasis progression through cell proliferation and inflammatory cytokine regulation.
  • Dual inhibition offers potential synergistic effects and reduced toxicity compared to single-target approaches.

Purpose of the Study:

  • To design and synthesize novel dual inhibitors of CDK6 and CDK9.
  • To explore compounds with enhanced interactions for potential anti-psoriatic activity.
  • To evaluate the therapeutic potential of dual CDK6/CDK9 inhibitors for psoriasis.

Main Methods:

  • Design and synthesis of 17 novel compounds based on a previously discovered lead.
  • Exploration of hydrogen bond interactions with CDK6 and CDK9.
  • In vitro evaluation of anti-inflammatory effects and pathway inhibition in IFN-γ/TNF-α-induced HaCaT cells.

Main Results:

  • Compound 4 demonstrated dual CDK6 and CDK9 inhibitory activity.
  • Compound 4 ameliorated inflammation in vitro.
  • Compound 4 inhibited the STAT3 pathway and reduced inflammatory factor mRNA levels.

Conclusions:

  • Dual CDK6 and CDK9 inhibitors show potential as therapeutic agents for psoriasis.
  • Compound 4 represents a promising candidate for further development.
  • Targeting both CDK6 and CDK9 offers a viable strategy for managing psoriasis.
Keywords:
Anti-inflammatoryBiological activityInhibitorPsoriasis

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

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

11.4K
Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules10:58

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

Published on: July 25, 2013

17.2K

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...
4.9K
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...
5.7K
Structure-Activity Relationships and Drug Design01:28

Structure-Activity Relationships and Drug Design

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...
1.1K
Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents01:29

Drugs for Treatment of Crohn's Disease in IBD Using Immunomodulatory Agents

Crohn's disease is an inflammatory bowel disorder marked by chronic inflammation of the GI tract. Various treatment strategies for Crohn's disease are employed, such as immunomodulatory agents, glucocorticoids, and biologics or anti-TNF therapy. Azathioprine (Imuran), a commonly used immunomodulatory drug for Crohn's disease, is converted in the body to mercaptopurine, which inhibits purine biosynthesis and cell proliferation. Both are utilized in severe cases of Inflammatory Bowel...
278
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.
5.7K
Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF01:24

Drugs for Treatment of Crohn's Disease in IBD Using Biologic Agents: Anti-TNF

Tumor Necrosis Factor (TNF), a proinflammatory cytokine, contributes significantly to the inflammation seen in Crohn's disease. It exists as soluble TNF and membrane-bound TNF, with actions mediated through TNF receptors (TNFR). TNFR activation leads to the release of proinflammatory cytokines, T-cell activation, collagen production, and leukocyte migration, all contributing to inflammation in Crohn's disease. Anti-TNF monoclonal antibodies, namely infliximab (Remicade), adalimumab...
240