Small-molecule inhibitors of 6-phosphofructo-1-kinase simultaneously suppress lactate and superoxide generation in cancer cells.

ABSTRACT: Deregulated energy metabolism is a hallmark of cancer, characterized by increased glycolytic flux. Cancer-specific modification of 6-phosphofructo-1-kinase (PFK) impairs its ability to regulate the enzyme's activity which increases glycolytic flux. Consequently, excessive cytosolic NADH formation triggers a harmful redox imbalance in cancer cells, which is rapidly neutralized by the formation of lactic acid and superoxide (SOX). To learn more about deregulated glycolysis in cancer cells, a supercomputer used the atomic model of the crystal structure of human PFK1 for virtual screening a database of 4.5 million compounds by docking with the catalytic binding sites of the enzyme. The screening revealed two compounds capable of reducing modified, cancer-specific PFK1 activity and simultaneous

SUBMITTER: Lesnik S 

PROVIDER: S-EPMC12094722 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature