Discovery of SHR5428 as a selective and noncovalent inhibitor of CDK7.
Bioorg Med Chem Lett
; 93: 129429, 2023 09 01.
Article
en En
| MEDLINE
| ID: mdl-37543274
ABSTRACT
Cyclin dependent kinase 7 (CDK7) is an attractive target in tumor indications via regulating both cell cycle and transcription. Here, SHR5428 was discovered as a selective and noncovalent CDK7 inhibitor with highly potent CDK7 enzymatic activity and triple negative breast cancer cellular activity on MDA-MB-468 cell. SHR5428 also displayed favorable pharmacokinetic properties in different preclinical species such as mouse, rat and dog, and showed high selectivity over CDK1, CDK2, CDK4, CDK6, CDK9, CDK12 in CDK family. Furthermore, the computational modeling has shed some light on this mechanism. Additionally the in vivo efficacy study in a breast cancer cell line (HCC70 cell) derived xenograft mouse model proved SHR5428 to be orally efficacious with dose-dependent tumor growth inhibition.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Inhibidores de Proteínas Quinasas
/
Quinasa Activadora de Quinasas Ciclina-Dependientes
Límite:
Animals
/
Humans
Idioma:
En
Año:
2023
Tipo del documento:
Article