Related Experiment Video

Updated: Jul 28, 2025

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

11.4K

Targeting CDK9 with selective inhibitors or degraders in tumor therapy: an overview of recent developments

Lanshu Xiao1,2, Yi Liu1, Hui Chen1

  • 1Department of Clinical Laboratory, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Cancer Biology & Therapy
|June 5, 2023
PubMed

Insights

Selective cyclin-dependent kinase 9 (CDK9) inhibitors and PROTAC degraders show promise in cancer therapy. Further research is needed to optimize their use in specific tumor types and combination treatments.

Area of Science:

  • Oncology
  • Molecular Biology
  • Drug Development

Background:

  • Cyclin-dependent kinase 9 (CDK9), a key component of the positive transcription elongation factor b (P-TEFb), plays a role in cancer development.
  • Targeting CDK9 offers a potential therapeutic strategy for various malignancies.

Purpose of the Study:

  • To review the development of selective CDK9 inhibitors and proteolysis-targeting chimera (PROTAC) degraders.
  • To summarize their structures, efficacy, mechanisms, and potential combination therapies.

Main Methods:

  • Literature review of selective CDK9 inhibitors and PROTAC degraders.
  • Analysis of preclinical and clinical data for identified compounds.

Main Results:

  • Twenty selective CDK9 inhibitors and degraders were identified, with detailed information on their properties.
  • Several inhibitors (NVP-2, MC180295, fadraciclib, KB-0742, LZT-106, 21e) are developed for solid tumors, often genotype-specific.
  • VIP152 demonstrated efficacy in clinical trials for advanced high-grade lymphoma and solid tumors.

Conclusions:

  • Selective CDK9 inhibitors and degraders represent a developing class of anti-cancer agents.
  • Identifying optimal tumor genotypes and combination strategies is crucial for clinical success.
  • Further investigation into molecular mechanisms is essential for advancing CDK9-targeted therapies.
Keywords:
CDK9PROTAC degradersdevelopmentsmall molecular inhibitorstargeted therapytumor

More Related Videos

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts10:27

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

7.3K
A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers10:49

A Murine Cell Line Based Model of Chronic CDK9 Inhibition to Study Widespread Non-Genetic Transcriptional Elongation Defects TEdeff in Cancers

Published on: September 26, 2019

5.7K

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...
4.8K
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...
5.6K
Targeted Cancer Therapies02:57

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
7.7K
Combination Therapies and Personalized Medicine02:50

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
5.0K
Tumor Immunotherapy01:27

Tumor Immunotherapy

Immunotherapy is a treatment that boosts or manipulates the immune system to fight diseases, including cancer. For instance, by stimulating an immune response through vaccinations against viruses that cause cancers, like hepatitis B virus and human papillomavirus, these diseases can be prevented. Nonetheless, some cancer cells can avoid the immune system due to their rapid mutation and division. The immune response to many cancers involves three phases: elimination, equilibrium, and escape.
575
Mitogens and the Cell Cycle02:38

Mitogens and the Cell Cycle

Mitogens and their receptors play a crucial role in controlling the progression of the cell cycle. However, the loss of mitogenic control over cell division leads to tumor formation. Therefore, mitogens and mitogen receptors play an important role in cancer research. For instance, the epidermal growth factor (EGF) - a type of mitogen and its transmembrane receptor (EGFR), decides the fate of the cell's proliferation. When EGF binds to EGFR, a member of the ErbB family of tyrosine kinase...
6.6K