The promise and current status of CDK12/13 inhibition for the treatment of cancer.
Future Med Chem
; 13(2): 117-141, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33295810
ABSTRACT
CDK12 and CDK13 are Ser/Thr protein kinases that regulate transcription and co-transcriptional processes. Genetic silencing of CDK12 is associated with genomic instability in a variety of cancers, including difficult-to-treat breast, ovarian, colorectal, brain and pancreatic cancers, and is synthetic lethal with PARP, MYC or EWS/FLI inhibition. CDK13 is amplified in hepatocellular carcinoma. Consequently, selective CDK12/13 inhibitors constitute powerful research tools as well as promising anti-cancer therapeutics, either alone or in combination therapy. Herein the authors discuss the role of CDK12 and CDK13 in normal and cancer cells, describe their utility as a biomarker and therapeutic target, review the medicinal chemistry optimization of existing CDK12/13 inhibitors and outline strategies for the rational design of CDK12/13 selective inhibitors.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
/
Quinases Ciclina-Dependentes
/
Inibidores de Proteínas Quinases
/
Neoplasias
/
Antineoplásicos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Future Med Chem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos