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Bazedoxifene analogs as potential WDHD1 degraders and antitumor agents: Synthesis, evaluation and molecular dynamics simulation studies.
Chen, Leyuan; Liu, Gaiting; Meng, Fancui; Shi, Yu; Fang, Zhennan; Peng, Zhenyu; Wang, Manjiang; Gou, Wenfeng; Hou, Wenbin; Li, Yiliang.
Afiliación
  • Chen L; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
  • Liu G; Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  • Meng F; Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin, China.
  • Shi Y; Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing, China.
  • Fang Z; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
  • Peng Z; Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  • Wang M; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
  • Gou W; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
  • Hou W; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
  • Li Y; Institute of Radiation Medicine, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, China.
Drug Dev Res ; 85(1): e22155, 2024 Feb.
Article en 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Simulación de Dinámica Molecular / Antineoplásicos Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: Drug Dev Res Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Simulación de Dinámica Molecular / Antineoplásicos Límite: Humans País/Región como asunto: America do norte Idioma: En Revista: Drug Dev Res Año: 2024 Tipo del documento: Article País de afiliación: China