Background: The aerobic glycolysis in tumor cells known as Warburg effect is one of the
most important hallmarks of cancer. It is proposed that the upregulation of the series of metabolic enzymes
along the glycolytic pathway may contribute to the Warburg effect.
Objectives: The inhibition of these glycolytic enzymes has been found to be a novel strategy for anticancer
treatment. This review summaries recent patents in the development of small molecule inhibitors
for the key enzymes in tumor glycolysis. The targeted enzymes are GLUTs, HKs, PFK, PGAM1,
PKM2, LDHA, MCTs and PDK.
Conclusion: Although most inhibitors are still in the preclinical phase, the inhibition of glycolytic enzymes represents a
very promising approach for anticancer treatment. The future development could be more focused on the discovery of new
metabolic enzyme that is specifically expressed in tumor cells.