2. Academic Validation
  3. Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation

Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation

  • Angew Chem Int Ed Engl. 2016 Sep 19;55(39):12035-9. doi: 10.1002/anie.201606121.
Qing-Li He 1,  Il Minn 2,  Qiaoling Wang 3,  Peng Xu 3,  Sarah A Head 1,  Emmanuel Datan 1,  Biao Yu 3,  Martin G Pomper 4,  Jun O Liu 5
Affiliations

Affiliations

  • 1 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.
  • 2 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
  • 3 Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, China.
  • 4 Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA. mpomper@jhmi.edu.
  • 5 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.
PMID: 27574181 DOI: 10.1002/anie.201606121
Abstract

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.

Keywords

antitumor agents; cytotoxicity; glucose transporters; prostate cancer; triptolide.

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