Your browser doesn't support javascript.
loading
c-Myc-Targeting PROTAC Based on a TNA-DNA Bivalent Binder for Combination Therapy of Triple-Negative Breast Cancer.
Li, Xintong; Zhang, Ze; Gao, Fangyan; Ma, Yuxuan; Wei, Dongying; Lu, Zhangwei; Chen, Siqi; Wang, Mengqi; Wang, Yueyao; Xu, Kun; Wang, Runtian; Xu, Feng; Chen, Jia-Yu; Zhu, Chengjun; Li, Zhe; Yu, Hanyang; Guan, Xiaoxiang.
Afiliación
  • Li X; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Zhang Z; State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Gao F; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Ma Y; State Key Laboratory of Analytical Chemistry for Life Science, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.
  • Wei D; State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Lu Z; State Key Laboratory of Analytical Chemistry for Life Science, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.
  • Chen S; State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Wang M; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Wang Y; State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Xu K; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Wang R; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Xu F; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Chen JY; State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Zhu C; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
  • Li Z; State Key Laboratory of Analytical Chemistry for Life Science, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.
  • Yu H; State Key Laboratory of Coordination Chemistry, Department of Biomedical Engineering, College of Engineering and Applied Sciences, Jiangsu Key Laboratory of Artificial Functional Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), Nanjing University, Nanjing 210023, China.
  • Guan X; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
J Am Chem Soc ; 145(16): 9334-9342, 2023 04 26.
Article en En | MEDLINE | ID: mdl-37068218
ABSTRACT
Triple-negative breast cancer (TNBC) is highly aggressive with a poor clinical prognosis and no targeted therapy. The c-Myc protein is a master transcription factor and a potential therapeutic target for TNBC. In this study, we develop a PROTAC (PROteolysis TArgeting Chimera) based on TNA (threose nucleic acid) and DNA that effectively targets and degrades c-Myc. The TNA aptamer is selected in vitro to bind the c-Myc/Max heterodimer and appended to the E-box DNA sequence to create a high-affinity, biologically stable bivalent binder. The TNA-E box-pomalidomide (TEP) conjugate specifically degrades endogenous c-Myc/Max, inhibits TNBC cell proliferation, and sensitizes TNBC cells to the cyclin-dependent kinase inhibitor palbociclib in vitro. In a mouse TNBC model, combination therapy with TEP and palbociclib potently suppresses tumor growth. This study offers a promising nucleic acid-based PROTAC modality for both chemical biology studies and therapeutic interventions of TNBC.
Asunto(s)
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Am Chem Soc Año: 2023 Tipo del documento: Article País de afiliación: China
Texto completo
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Neoplasias de la Mama Triple Negativas / Antineoplásicos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: J Am Chem Soc Año: 2023 Tipo del documento: Article País de afiliación: China