title: CDK8 kinase--An emerging target in targeted cancer therapy.
abstract: Cyclin-dependent kinase (CDK) inhibitors have been developed as potential anticancer therapeutics and several nonselective compounds are currently in advanced clinical trials. This review is focused on the key biological roles of CDK8 kinase, which provide a proof-of-principle for continued efforts toward effective cancer treatment, targeting activity of this CDK family member. Among currently identified kinase inhibitors, several displayed significant selectivity for CDK8 and notably the effectiveness in targeting cancer specific gene expression programs. Structural features of CDK8 and available ligands were discussed from a perspective of the rational drug design process. Current state of the art confirms that further development of CDK8 inhibitors will translate into targeted therapies in oncology. This article is part of a Special Issue entitled:Inhibitors of Protein Kinases.
authors.affiliation: Selvita SA, Kraków, Poland. Electronic address: krzysztof.brzozka@selvita.com.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Rzymski
authors.affiliation: Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Mikula
authors.affiliation: Selvita SA, Kraków, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Wiklik
authors.affiliation: Selvita SA, Kraków, Poland. Electronic address: Krzysztof.brzozka@selvita.com.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Brzózka
mesh_terms: D056850:Cyclin-Dependent Kinase 8 / Q000037:antagonists & inhibitors* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009536:Niacinamide / Q000031:analogs & derivatives / Q000737:chemistry / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000737:chemistry / Q000627:therapeutic use; D011487:Protein Conformation; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D000077157:Sorafenib; D014158:Transcription, Genetic / Q000187:drug effects*
chemical_list: D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D009536:Niacinamide; D000077157:Sorafenib; C095686:CDK8 protein, human; D056850:Cyclin-Dependent Kinase 8
keywords: CDK8 kinase; Cancer; Kinase inhibitors; Novel therapies; Transcription regulation