Related Experiment Video
Updated: Jan 23, 2026
Identification of Cyclin-dependent Kinase 1 Specific Phosphorylation Sites by an In Vitro Kinase Assay
Published on: May 3, 2018
Inhibitors of Cyclin-Dependent Kinase 1/2 for Anticancer Treatment
Jiajia Mou1, Danghui Chen1, Yanru Deng1
1Department of Medicinal Chemistry, School of Chinese Materia Medica, Tianjin University of Traditional Chinese Medicine, Health Industry Park, Jinghai District, Tianjin, 301617, China.
Background:
The cell cycle is regulated by cyclin-dependent kinases (CDKs) and their cognate cyclins, along with their endogenous inhibitors (CDKIs). CDKs act as central regulators in this process. Different CDKs play relevant roles in different phases. Among all CDKs, CDK1 is indispensible, which can drive all events that are required in the cell cycle in the absence of interphase CDKs (CDK2, CDK3, CDK4 and CDK6). So, CDK1 is an attractive target for anticancer drug development.
Methods:
CDK1 and CDK2 have 89.19% similar residues and 74.32% identical residues, their structures especially the ATP-binding sites are of great similarity. So, it is difficult to inhibit CDK1 and CDK2 individually. In this review, recent advances about CDK1/2 inhibitors were summarized. The chemical structures of different classes of CDK1/2 inhibitors and their structure activity are presented.
Results:
19 kinds of CDK1/2 or CDK1 inhibitors with different scaffolds, including CDK2 allosteric inhibitors, were summarized. Some inhibitors are nature derived, for example, phenanthrene derivatives, nortopsentin derivatives, variolin B derivatives and meridians.
Conclusion:
Nature products, especially marine ones are potential resources for CDK1 inhibitors development. The findings of CDK2 allosteric inhibitors open an avenue to the discovery of novel selective CDK1 or other CDKs allosteric inhibitors.
Insights
Cyclin-dependent kinase 1 (CDK1) is crucial for cell cycle progression and a target for cancer drugs. This review summarizes CDK1/2 inhibitors, highlighting natural products as promising sources for developing selective CDK1 inhibitors.
Area of Science:
- Biochemistry
- Molecular Biology
- Pharmacology
Background:
- Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs), cyclins, and CDK inhibitors (CDKIs).
- CDK1 is essential for all cell cycle phases, making it a key target for anticancer drug development.
- CDK1 and CDK2 share significant structural similarity, particularly in ATP-binding sites, complicating selective inhibition.
Purpose of the Study:
- To review recent advancements in the development of CDK1 and CDK1/2 inhibitors.
- To present the chemical structures and structure-activity relationships of various CDK1/2 inhibitor classes.
- To explore the potential of natural products as sources for novel CDK1 inhibitors.
Main Methods:
- Literature review summarizing existing CDK1/2 and CDK1 inhibitors.
- Analysis of chemical structures and structure-activity relationships of different inhibitor classes.
- Identification of nature-derived compounds with inhibitory activity against CDK1/2.
Main Results:
- Summarized 19 types of CDK1/2 or CDK1 inhibitors with diverse scaffolds.
- Included CDK2 allosteric inhibitors in the summary.
- Identified nature-derived inhibitors, such as phenanthrene, nortopsentin, variolin B, and meridine derivatives.
Conclusions:
- Natural products, particularly marine-derived compounds, represent a valuable resource for developing CDK1 inhibitors.
- The discovery of CDK2 allosteric inhibitors provides a pathway for developing novel selective allosteric inhibitors for CDK1 and other CDKs.
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