Your browser doesn't support javascript.
loading
Metabolic glycoengineering sensitizes drug-resistant pancreatic cancer cells to tyrosine kinase inhibitors erlotinib and gefitinib.
Mathew, Mohit P; Tan, Elaine; Saeui, Christopher T; Bovonratwet, Patawut; Liu, Lingshu; Bhattacharya, Rahul; Yarema, Kevin J.
Afiliação
  • Mathew MP; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA.
  • Tan E; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA.
  • Saeui CT; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA.
  • Bovonratwet P; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA.
  • Liu L; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA.
  • Bhattacharya R; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA.
  • Yarema KJ; Department of Biomedical Engineering and the Translational Tissue Engineering Center, The Johns Hopkins University, 5029 Robert H. & Clarice Smith Building, 400 North Broadway, Baltimore, MD 21231, USA. Electronic address: kyarema1@jhu.edu.
Bioorg Med Chem Lett ; 25(6): 1223-7, 2015 Mar 15.
Article em En | MEDLINE | ID: mdl-25690786
Metastatic human pancreatic cancer cells (the SW1990 line) that are resistant to the EGFR-targeting tyrosine kinase inhibitor drugs (TKI) erlotinib and gefitinib were treated with 1,3,4-O-Bu3ManNAc, a 'metabolic glycoengineering' drug candidate that increased sialylation by ∼2-fold. Consistent with genetic methods previously used to increase EGFR sialylation, this small molecule reduced EGF binding, EGFR transphosphorylation, and downstream STAT activation. Significantly, co-treatment with both the sugar pharmacophore and the existing TKI drugs resulted in strong synergy, in essence re-sensitizing the SW1990 cells to these drugs. Finally, 1,3,4-O-Bu3ManNAz, which is the azido-modified counterpart to 1,3,4-O-Bu3ManNAc, provided a similar benefit thereby establishing a broad-based foundation to extend a 'metabolic glycoengineering' approach to clinical applications.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinazolinas / Inibidores de Proteínas Quinases / Engenharia Metabólica / Cloridrato de Erlotinib Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinazolinas / Inibidores de Proteínas Quinases / Engenharia Metabólica / Cloridrato de Erlotinib Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Estados Unidos