Essays in biochemistry, 2017-11, Vol.61 (5), p.439-452
2017
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- Autor(en) / Beteiligte
- Titel
- Structure-based discovery of cyclin-dependent protein kinase inhibitors
- Ist Teil von
- Essays in biochemistry, 2017-11, Vol.61 (5), p.439-452
- Ort / Verlag
- England
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- The cell fate-determining roles played by members of the cyclin-dependent protein kinase (CDK) family explain why their dysregulation can promote proliferative diseases, and identify them as potential targets for drug discovery in oncology and beyond. After many years of research, the first efficacious CDK inhibitors have now been registered for clinical use in a defined segment of breast cancer. Research is underway to identify inhibitors with appropriate CDK-inhibitory profiles to recapitulate this success in other disease settings. Here, we review the structural data that illustrate the interactions and properties that confer upon inhibitors affinity and/or selectivity toward different CDK family members. We conclude that where CDK inhibitors display selectivity, that selectivity derives from exploiting active site sequence peculiarities and/or from the capacity of the target CDK(s) to access conformations compatible with optimizing inhibitor-target interactions.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0071-1365eISSN: 1744-1358DOI: 10.1042/EBC20170040Titel-ID: cdi_pubmed_primary_29118092
- Format
- –
- Schlagworte
- Antineoplastic Agents - chemical synthesis, Antineoplastic Agents - pharmacology, Catalytic Domain, Cyclin-Dependent Kinases - antagonists & inhibitors, Cyclin-Dependent Kinases - chemistry, Cyclin-Dependent Kinases - metabolism, Drug Discovery - methods, Humans, Molecular Docking Simulation, Molecular Targeted Therapy, Neoplasm Proteins - antagonists & inhibitors, Neoplasm Proteins - chemistry, Neoplasm Proteins - metabolism, Neoplasms - drug therapy, Neoplasms - enzymology, Neoplasms - genetics, Neoplasms - pathology, Protein Binding, Protein Conformation, alpha-Helical, Protein Conformation, beta-Strand, Protein Interaction Domains and Motifs, Protein Kinase Inhibitors - chemical synthesis, Protein Kinase Inhibitors - pharmacology, Structure-Activity Relationship