The progress and development of GLUT1 inhibitors targeting cancer energy metabolism

Future Med Chem. 2019 Sep;11(17):2333-2352. doi: 10.4155/fmc-2019-0052.

Abstract

A major difference between glucose metabolism in cancer cells and normal cells is that glucose in cancer cells is preferably converted to lactate in aerobic conditions rather than oxidized in mitochondria. This process is called aerobic glycolysis, known as the 'Warburg effect'. In this review, we focus on the energy-metabolism characteristics between tumor and normal cells, analyzing the regulation mechanism of energy metabolism based on glycolysis, and summarizing two targets on the upstream proteins of glycolysis, including glucose transporter (GLUT) and hexokinase. In addition, we proposed the risks and limitations of GLUT1-based drug research and summarized the current research progress of representative drugs, including natural and synthetic GLUT1 inhibitors. This will provide guidance for designing and synthesizing small molecule drugs targeting GLUT1 in glycolysis.

Keywords: GLUT1 inhibitors; aerobic glycolysis; cancer energy metabolism.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Drug Design
  • Energy Metabolism / drug effects*
  • Gene Expression Regulation, Neoplastic
  • Glucose Transporter Type 1 / antagonists & inhibitors*
  • Glucose Transporter Type 1 / metabolism
  • Glycolysis / drug effects
  • Hexokinase / metabolism
  • Humans
  • Mitochondria / drug effects
  • Molecular Structure
  • Organic Chemicals / chemistry*
  • Organic Chemicals / pharmacology
  • Structure-Activity Relationship
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Glucose Transporter Type 1
  • Organic Chemicals
  • Hexokinase