Discovery and Development of Cyclin-Dependent Kinase 8 Inhibitors.
CDK19
CDK8
CDK8 inhibitors
Cyclin-dependent Kinases
Design
Metabolic stability
Selective inhibitors
Structure-activity relationship.
Journal
Current medicinal chemistry
ISSN: 1875-533X
Titre abrégé: Curr Med Chem
Pays: United Arab Emirates
ID NLM: 9440157
Informations de publication
Date de publication:
2020
2020
Historique:
received:
29
12
2018
revised:
20
02
2019
accepted:
20
03
2019
pubmed:
6
4
2019
medline:
24
11
2020
entrez:
6
4
2019
Statut:
ppublish
Résumé
Cyclin-dependent Kinase 8 (CDK8), a member of the CDKs family, has been widely focused owing to investigations of its critical roles in transcription and oncogenesis in recent years. Selective inhibition of CDK8 and its paralog CDK19 offers a novel therapeutic strategy for the treatment of some cancers. Up to now, though many small molecules against CDK8 have been discovered, most of them are discontinued in the preclinical trials due to the low selectivity and poor physicochemical properties. This review mainly summarizes the design strategies of selective CDK8 inhibitors having different chemical scaffolds with the aim to improve the inhibitory activity, selectivity, metabolic stability and solubility. Their corresponding Structure-activity Relationships (SAR) are also reviewed. On the basis of the discussion in this review, we hope more effective, selective and drug-like CDK8 inhibitors will be developed and demonstrate therapeutic values in the near future.
Identifiants
pubmed: 30947649
pii: CMC-EPUB-97744
doi: 10.2174/0929867326666190402110528
doi:
Substances chimiques
Protein Kinase Inhibitors
0
Cyclin-Dependent Kinase 8
EC 2.7.11.22
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
5429-5443Informations de copyright
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