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Progress in Chemistry 2020, Vol. 32 Issue (12): 1869-1878 DOI: 10.7536/PC200420   Next Articles

• Review •

Development of Anticancer Drugs Targeting Glucose Transporters(GLUTs)

Ziru Sun1, Shengnan Liu1,2,**(), Qingzhi Gao1,**()   

  1. 1 School of Pharmaceutical Science and Technology, Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, Tianjin University, Tianjin 300072, China
    2 Institute of Molecular Plus, Tianjin University, Tianjin 300072, China
  • Received: Revised: Online: Published:
  • Contact: Shengnan Liu, Qingzhi Gao
  • Supported by:
    the National Natural Science Foundation of China(No. 21772144)
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Increased glycolysis in malignant tumors has been one of the hallmarks and biotargets of tumor targeting that enable the design and development of novel targeted therapy agents. In this review, by focusing on the Warburg effect-targeted drug discovery and the unique concepts for development of glucose transporters(GLUTs)-targeted anticancer agents, we examine the current scenario with a brief introduction of anticancer GLUTs inhibitors and glycoconjugated antitumor examples, to provide an overview of studies of the Warburg effect-targeted anticancer drug development, the design strategy and useful perspectives for new-generation of targeted chemotherapeutic agents.

Contents

1 Introduction

2 Glucose transporters

3 Research status of anticancer targeted drugs utilizing the Warburg effect

3.1 GLUTs inhibitors

3.2 Glycoconjugates for tumor targeting

4 Conclusion and outlook

Key words: Warburg effect, glucose transporters, targeted anti-cancer therapy, glycoconjugated anticancer agents
Fig.1 (a) Schematic diagram of normal cell metabolism.(b) Schematic diagram of cancer cell metabolism
Fig.2 Representative natural compounds as GLUT inhibitors
Fig.3 Representative of GLUTs inhibitors in preclinical in vitro studies, (a) GLUT1 inhibitors,(b) GLUT1 and GLUT3 inhibitor,(c) GLUT4 inhibitor,(d) GLUT5 inhibitor
Fig.4 Representative of GLUTs inhibitors in preclinical in vivo studies
Fig.5 Representative glucose analogs
Table 1 Several cancer clinical trials with 2-DG[57 ? ?~60]
Phases Combined therapy Diseases Status
Phase Ⅲ — Prostate cancer Terminated(Has results)
Phase Ⅰ Docetaxel Lung/Breast/Head and neck cancer Completed
Phase Ⅰ Radiotherapy Glioblastoma multiforme —
Phase Ⅲ Radiotherapy Cerebal gliomas —
Fig.6 Representative glycoconjugates
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