Transcriptional regulation and therapeutic potential of cyclin-dependent kinase 9 (CDK9) in sarcoma

Walker, Robert L.; Hornicek, Francis J.; Duan, Zhenfeng

doi:10.1016/j.bcp.2024.116342

Biochemical Pharmacology

2024

DOI: 10.1016/j.bcp.2024.116342

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Transcriptional regulation and therapeutic potential of cyclin-dependent kinase 9 (CDK9) in sarcoma

Robert L. Walker,

Francis J. Hornicek,

Zhenfeng Duan

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2024

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Cited by 2 publications

References 184 publications

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Heterocyclic Compounds as CDK9 Inhibitors: Structural Diversity, Mechanism of Action, and Therapeutic Potential in Cancer and Beyond

Bose,

Shajahan,

Sreekumar

et al. 2024

Chemistry & Biodiversity

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Cyclin‐dependent kinases (CDKs) are crucial proteins involved in key cellular processes, such as cell division and transcription. Their dysregulation plays a significant role in cancer development. Inhibiting cyclin‐dependent kinase 9 (CDK9) impacts several survival pathways in cancer cells, presenting a promising therapeutic approach for various cancers. CDK9, in association with cyclin T1, forms the positive transcription elongation factor b (P‐TEFb) complex, which phosphorylates the C‐terminal domain (CTD) of RNA polymerase II (Pol II). This phosphorylation promotes the transition from transcription initiation to elongation. This review examines recent advancements in CDK9 modulators, with a particular emphasis on compounds currently in clinical trials.

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Heterocyclic Compounds as CDK9 Inhibitors: Structural Diversity, Mechanism of Action, and Therapeutic Potential in Cancer and Beyond

Bose,

Shajahan,

Sreekumar

et al. 2024

Chemistry & Biodiversity

View full text Add to dashboard Cite

show abstract

Advances in Cancer Therapy: A Comprehensive Review of CDK and EGFR Inhibitors

Hawash

2024

Cells

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Protein kinases have essential responsibilities in controlling several cellular processes, and their abnormal regulation is strongly related to the development of cancer. The implementation of protein kinase inhibitors has significantly transformed cancer therapy by modifying treatment strategies. These inhibitors have received substantial FDA clearance in recent decades. Protein kinases have emerged as primary objectives for therapeutic interventions, particularly in the context of cancer treatment. At present, 69 therapeutics have been approved by the FDA that target approximately 24 protein kinases, which are specifically prescribed for the treatment of neoplastic illnesses. These novel agents specifically inhibit certain protein kinases, such as receptor protein-tyrosine kinases, protein-serine/threonine kinases, dual-specificity kinases, nonreceptor protein-tyrosine kinases, and receptor protein-tyrosine kinases. This review presents a comprehensive overview of novel targets of kinase inhibitors, with a specific focus on cyclin-dependent kinases (CDKs) and epidermal growth factor receptor (EGFR). The majority of the reviewed studies commenced with an assessment of cancer cell lines and concluded with a comprehensive biological evaluation of individual kinase targets. The reviewed articles provide detailed information on the structural features of potent anticancer agents and their specific activity, which refers to their ability to selectively inhibit cancer-promoting kinases including CDKs and EGFR. Additionally, the latest FDA-approved anticancer agents targeting these enzymes were highlighted accordingly.

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Transcriptional regulation and therapeutic potential of cyclin-dependent kinase 9 (CDK9) in sarcoma

Cited by 2 publications

References 184 publications

Heterocyclic Compounds as CDK9 Inhibitors: Structural Diversity, Mechanism of Action, and Therapeutic Potential in Cancer and Beyond

Heterocyclic Compounds as CDK9 Inhibitors: Structural Diversity, Mechanism of Action, and Therapeutic Potential in Cancer and Beyond

Advances in Cancer Therapy: A Comprehensive Review of CDK and EGFR Inhibitors

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