Identification of a Small-Molecule Glucose Transporter Inhibitor, Glutipyran, That Inhibits Cancer Cell Growth

ACS Chem Biol. 2021 Aug 20;16(8):1576-1586. doi: 10.1021/acschembio.1c00480. Epub 2021 Jul 23.


Cancer cells reprogram their metabolism to survive and grow. Small-molecule inhibitors targeting cancer are useful for studying its metabolic pathways and functions and for developing anticancer drugs. Here, we discovered that glutipyran and its derivatives inhibit glycolytic activity and cell growth in human pancreatic cancer cells. According to proteomic profiling of glutipyran-treated cells using our ChemProteoBase, glutipyran was clustered within the group of endoplasmic reticulum (ER) stress inducers that included glycolysis inhibitors. Glutipyran inhibited glucose uptake and suppressed the growth of various cancer cells, including A431 cells that express glucose transporter class I (GLUT1) and DLD-1 GLUT1 knockout cells. When cotreated with the mitochondrial respiration inhibitor metformin, glutipyran exhibited a synergistic antiproliferative effect. Metabolome analysis revealed that glutipyran markedly decreased most metabolites of the glycolytic pathway and the pentose phosphate pathway. Glutipyran significantly suppressed tumor growth in a xenograft mouse model of pancreatic cancer. These results suggest that glutipyran acts as a broad-spectrum GLUT inhibitor and reduces cancer cell growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Drug Synergism
  • Female
  • Glucose / metabolism
  • Glucose Transport Proteins, Facilitative / antagonists & inhibitors*
  • Glycolysis / drug effects
  • Humans
  • Metabolomics
  • Metformin / therapeutic use
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasms / drug therapy*
  • Proteomics
  • Pyrans / chemical synthesis
  • Pyrans / pharmacology
  • Pyrans / therapeutic use*
  • Xenograft Model Antitumor Assays


  • Antineoplastic Agents
  • Glucose Transport Proteins, Facilitative
  • Pyrans
  • Metformin
  • Glucose