Related Experiment Video

Updated: Jan 26, 2026

Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
12:26

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

Published on: May 3, 2018

19.3K

Discovery and Development of Cyclin-Dependent Kinase 8 Inhibitors

Xiao Lv1, Yongbing Tian1, Shiyu Li1

  • 1School of Food and Biological Engineering, Hefei University of Technology, Hefei, Anhui 230009, China.

Current Medicinal Chemistry
|April 6, 2019
PubMed

Insights

This review focuses on developing selective Cyclin-dependent Kinase 8 (CDK8) inhibitors for cancer therapy. It summarizes design strategies and structure-activity relationships to overcome limitations of current drug candidates.

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Oncology

Background:

  • Cyclin-dependent Kinase 8 (CDK8) plays critical roles in transcription and oncogenesis.
  • Selective inhibition of CDK8 and CDK19 presents a promising cancer therapeutic strategy.
  • Existing CDK8 inhibitors often face challenges with selectivity and drug-like properties.

Purpose of the Study:

  • To review design strategies for selective CDK8 inhibitors.
  • To analyze Structure-Activity Relationships (SAR) for improved drug candidates.
  • To guide the development of more effective and drug-like CDK8 inhibitors.

Main Methods:

  • Literature review of CDK8 inhibitor research.
  • Analysis of chemical scaffolds and their impact on selectivity.
  • Evaluation of SAR data for optimizing inhibitor properties.

Main Results:

  • Various chemical scaffolds have been explored for CDK8 inhibition.
  • Design strategies aim to enhance inhibitory activity, selectivity, and physicochemical properties.
  • SAR studies reveal key modifications for improving metabolic stability and solubility.

Conclusions:

  • Overcoming selectivity and property limitations is crucial for CDK8 inhibitors.
  • Continued research into design strategies and SAR is essential.
  • Development of effective, selective, and drug-like CDK8 inhibitors holds therapeutic potential for cancer treatment.
Keywords:
CDK19CDK8CDK8 inhibitorsCyclin-dependent KinasesDesignMetabolic stabilitySelective inhibitorsStructure-activity relationship.

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

11.8K
Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays13:22

Kinase Inhibitor Screening In Self-assembled Human Protein Microarrays

Published on: October 23, 2019

8.3K

Related Concept Videos

cAMP-dependent Protein Kinase Pathways01:25

cAMP-dependent Protein Kinase Pathways

Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.4K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

Proteins undergo chemical modifications that trigger changes in the charge, structure, and conformation of the proteins. Phosphorylation, acetylation, glycosylation, nitrosylation, ubiquitination, lipidation, methylation, and proteolysis are various protein modifications that regulate protein activity. Such modifications are usually enzyme-driven.
Protein kinases
Many proteins in the cell are regulated by phosphorylation, the addition of a phosphate group. A family of enzymes called kinases...
15.0K
Protein Kinases and Phosphatases02:54

Protein Kinases and Phosphatases

4.4K
Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers01:26

Treatment for Pulmonary Arterial Hypertension: Receptor Tyrosine Kinase Inhibitors and Calcium Channel Blockers

Receptor tyrosine kinase inhibitors (TKIs) and calcium channel blockers (CCBs) are two critical categories of drugs employed in the treatment of pulmonary artery hypertension (PAH). PAH is a disease that causes high blood pressure in the pulmonary arteries, resulting in chest pain, fatigue, and shortness of breath.
TKIs, such as imatinib (Gleevec), are particularly effective in tackling the growth and mitogenic factors that become upregulated in PAH patients. These factors contribute to the...
491
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.9K
Drug Discovery: Overview01:26

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...
11.3K