Strategies of Targeting CK2 in Drug Discovery: Challenges, Opportunities, and Emerging Prospects.
Yijia ChenYu-Xi WangJiaxing WangZhilan ZhouShu CaoJifa ZhangPublished in: Journal of medicinal chemistry (2023)
CK2 (casein kinase 2) is a serine/threonine protein kinase that is ubiquitous in eukaryotic cells and plays important roles in a variety of cellular functions, including cell growth, apoptosis, circadian rhythms, DNA damage repair, transcription, and translation. CK2 is involved in cancer pathogenesis and the occurrence of many diseases. Therefore, targeting CK2 is a promising therapeutic strategy. Although many CK2-specific small-molecule inhibitors have been developed, only CX-4945 has progressed to clinical trials. In recent years, novel CK2 inhibitors have gradually become a research hotspot, which is expected to overcome the limitations of traditional inhibitors. Herein, we summarize the structure, biological functions, and disease relevance of CK2 and emphatically analyze the structure-activity relationship (SAR) and binding modes of small-molecule CK2 inhibitors. We also discuss the latest progress of novel strategies, providing insights into new drugs targeting CK2 for clinical practice.
Keyphrases
- protein kinase
- small molecule
- clinical trial
- dna damage
- oxidative stress
- cell cycle arrest
- drug discovery
- clinical practice
- randomized controlled trial
- risk assessment
- cell death
- squamous cell carcinoma
- transcription factor
- lymph node metastasis
- cell proliferation
- young adults
- binding protein
- dna binding
- open label
- tyrosine kinase