A patent review of selective CDK9 inhibitors in treating cancer
Tizhi Wu1, Xiaowei Wu1, Yifan Xu1
1State Key Laboratory of Natural Medicines and Jiang Su Key Laboratory of Drug Design and Optimization, Department of Medicinal Chemistry, School of Pharmacy, China Pharmaceutical University, Nanjing, China.
Introduction:
The dysregulation of CDK9 protein is greatly related to the proliferation and differentiation of various cancers due to its key role in the regulation of RNA transcription. Moreover, CDK9 inhibition can markedly downregulate the anti-apoptotic protein Mcl-1 which is essential for the survival of tumors. Thus, targeting CDK9 is considered to be a promising strategy for antitumor drug development, and the development of selective CDK9 inhibitors has gained increasing attention.
Areas Covered:
This review focuses on the development of selective CDK9 inhibitors reported in patent publications during the period 2020-2022, which were searched from SciFinder and Cortellis Drug Discovery Intelligence.
Expert Opinion:
Given that pan-CDK9 inhibitors may lead to serious side effects due to poor selectivity, the investigation of selective CDK9 inhibitors has attracted widespread attention. CDK9 inhibitors make some advance in treating solid tumors and possess the therapeutic potential in EGFR-mutant lung cancer. CDK9 inhibitors with short half-life and intravenous administration might result in transient target engagement and contribute to a better safety profile in vivo. However, more efforts are urgently needed to accelerate the development of CDK9 inhibitors, including the research on new binding modes between ligand and receptor or new protein binding sites.
Insights
Selective CDK9 inhibitors show promise for cancer treatment by targeting RNA transcription and Mcl-1. Recent patents (2020-2022) highlight advancements in developing these targeted therapies for improved antitumor drug development.
Area of Science:
- Oncology
- Molecular Biology
- Drug Discovery
Background:
- Cyclin-dependent kinase 9 (CDK9) dysregulation is linked to cancer proliferation and differentiation.
- CDK9 inhibition downregulates Mcl-1, a protein crucial for tumor survival.
- Targeting CDK9 is a promising strategy for developing novel antitumor drugs.
Purpose of the Study:
- To review the development of selective CDK9 inhibitors reported in patent literature from 2020 to 2022.
- To highlight advancements in selective CDK9 inhibitor research for cancer therapy.
Main Methods:
- Literature search of patent publications from 2020-2022.
- Utilized SciFinder and Cortellis Drug Discovery Intelligence databases.
Main Results:
- Selective CDK9 inhibitors are gaining attention due to potential side effects of pan-CDK9 inhibitors.
- CDK9 inhibitors show progress in treating solid tumors and have potential in EGFR-mutant lung cancer.
- Short half-life and intravenous administration may improve safety profiles.
Conclusions:
- Further research is needed to accelerate the development of selective CDK9 inhibitors.
- Exploring novel binding modes and protein interaction sites is crucial for future drug design.
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