Bazedoxifene analogs as potential WDHD1 degraders and antitumor agents: Synthesis, evaluation and molecular dynamics simulation studies.
Drug Dev Res
; 85(1): e22155, 2024 Feb.
Article
em En
| MEDLINE
| ID: mdl-38349257
ABSTRACT
DNA repair is strongly associated with tumor resistance to radiotherapy and chemotherapy. WD repeat and HMG-box DNA binding protein 1 (WDHD1) is a key adaptor for homologous recombination repair of DNA, and its overexpression is relevant to the poor prognosis of many tumor patients. We previously have identified and validated bazedoxifene (BZA), which had 60% inhibitory rate on WDHD1 in MCF7 cells at 10 µM, from the Food and Drug Administration-approved compound library. Here, we initially established the binding model of BZA, synthesized and evaluated eight BZA analogs. Further, we detailed the use of molecular dynamics simulations to provide insights into the basis for activity against WDHD1. This binding mode will be instructive for the development of new WDHD1 degraders.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Simulação de Dinâmica Molecular
/
Antineoplásicos
Limite:
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Drug Dev Res
Ano de publicação:
2024
Tipo de documento:
Article
País de afiliação:
China