Deregulation of cyclin-dependent kinases (CDKs) has been associated with many cancer types and has evoked an interest in chemical inhibitors with possible therapeutic benefit. While most known inhibitors display broad selectivity towards multiple CDKs, recent work highlights CDK9 as the critical target responsible for the anticancer activity of clinically evaluated drugs. In this review, we discuss recent findings provided by structural biologists that may allow further development of highly specific inhibitors of CDK9 towards applications in cancer therapy. We also highlight the role of CDK9 in inflammatory processes and diseases.
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http://dx.doi.org/10.2174/138161212800672750 | DOI Listing |
Med Chem
January 2025
Key Laboratory of Traditional Chinese Medicine Research and Development of Hebei Province, Institute of Traditional Chinese Medicine, Chengde Medical University, Chengde 067000, P.R. China.
Cyclin-Dependent Kinase (CDK) 12 is a member of the 20-membered CDK family (CDK1-20) and plays a vital role in regulating gene transcription, mRNA splicing, translation, cell cycle, and repair of DNA damage. CDK12 is an emerging therapeutic target due to its role in regulating the transcription of DNA Damage Response (DDR) genes in Cyclin-Dependent Kinase (CDK). However, the development of selective small molecules targeting CDK12 has been challenging due to the high degree of homology between kinase domains of CDK12 and other transcriptional CDKs, most notably CDK13.
View Article and Find Full Text PDFMol Biol Rep
January 2025
Institute of Pathogenic Biology, Guilin Medical University, Guilin, 541199, China.
Cyclin-dependent kinase 5 (CDK5), a unique member of the CDK family, is a proline-directed serine/threonine protein kinase with critical roles in various physiological and pathological processes. Widely expressed in the central nervous system, CDK5 is strongly implicated in neurological diseases. Beyond its neurological roles, CDK5 is involved in metabolic disorders, psychiatric conditions, and tumor progression, contributing to processes such as proliferation, migration, immune evasion, genomic stability, and angiogenesis.
View Article and Find Full Text PDFClin Drug Investig
January 2025
Department of Public Health Sciences, University of Virginia, 560 Ray C Hunt Dr., Room 2107, Charlottesville, VA, USA.
Background And Objective: Cyclin-dependent kinase (CDK)4/6 inhibitors in combination with endocrine therapy (ET) significantly enhance progression-free survival and overall survival in patients diagnosed with HR+/HER2- metastatic breast cancer (MBC). However, they are highly expensive, and their economic impact has not been fully evaluated. This is a retrospective secondary analysis evaluating the cost effectiveness of these drugs, differentiating between medication-related and non-medication costs from a healthcare perspective.
View Article and Find Full Text PDFQuant Plant Biol
December 2024
Department of Biology, Howard University, Washington, DC, USA.
Bioorg Chem
January 2025
Department of General Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China; Department of Thyroid and Breast Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China. Electronic address:
Breast cancer is the most prevalent malignant tumour among women. Approximately 70 % of patients are hormone receptor (HR)-positive and undergo endocrine therapy as the main form of treatment; however, the efficacy of this type of therapy is limited by some factors, such as drug resistance and complex tumour microenvironments. Using network pharmacology and molecular docking, this study examined how CDK4/6 inhibitors enhance the effects of immunotherapy for HR-positive breast cancer, focusing on their effects on the tumour microenvironment (TME) and immune cell activity.
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