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Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation.
He, Qing-Li; Minn, Il; Wang, Qiaoling; Xu, Peng; Head, Sarah A; Datan, Emmanuel; Yu, Biao; Pomper, Martin G; Liu, Jun O.
Afiliação
  • He QL; Department of Pharmacology, SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Hunterian Building, Room 516, Baltimore, MD, 21205, USA.
  • Minn I; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
  • Wang Q; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
  • Xu P; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
  • Head SA; Department of Pharmacology, SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Hunterian Building, Room 516, Baltimore, MD, 21205, USA.
  • Datan E; Department of Pharmacology, SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Hunterian Building, Room 516, Baltimore, MD, 21205, USA.
  • Yu B; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
  • Pomper MG; Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. mpomper@jhmi.edu.
  • Liu JO; Department of Pharmacology, SJ Yan and HJ Mao Laboratory of Chemical Biology, Johns Hopkins School of Medicine, 725 North Wolfe Street, Hunterian Building, Room 516, Baltimore, MD, 21205, USA. joliu@jhu.edu.
Angew Chem Int Ed Engl ; 55(39): 12035-9, 2016 09 19.
Article em En | MEDLINE | ID: mdl-27574181
Triptolide, a key ingredient from the traditional Chinese medicinal plant thunder god vine, which has been used to treat inflammation and autoimmune diseases for centuries, has been shown to be an irreversible inhibitor of the XPB subunit of the transcription factor TFIIH and initiation of RNA polymerase II mediated transcription. The clinical development of triptolide over the past two decades has been limited by its toxicity and low water solubility. Herein, we report the development of a glucose conjugate of triptolide, named glutriptolide, which was intended to target tumor cells overexpressing glucose transporters selectively. Glutriptolide did not inhibit XPB activity in vitro but demonstrated significantly higher cytotoxicity against tumor cells over normal cells with greater water solubility than triptolide. Furthermore, it exhibited remarkable tumor control in vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. These findings indicate that glutriptolide may serve as a promising lead for developing a new mechanistic class of anticancer drugs.
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Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Fenantrenos / Sistemas de Liberação de Medicamentos / Diterpenos / Glucose / Neoplasias / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: Angew Chem Int Ed Engl Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Temas: Geral / Tipos_de_cancer / Outros_tipos Base de dados: MEDLINE Assunto principal: Fenantrenos / Sistemas de Liberação de Medicamentos / Diterpenos / Glucose / Neoplasias / Antineoplásicos Limite: Animals / Humans Idioma: En Revista: Angew Chem Int Ed Engl Ano de publicação: 2016 Tipo de documento: Article País de afiliação: Estados Unidos