Non-orthosteric inhibition of enolase 1 impedes growth of triple-negative breast cancer.

ABSTRACT: Cancer cells exploit and overexpress glycolytic enzymes such as enolase 1 (ENO1) to sustain the Warburg effect, a hallmark of cancer metabolism, which makes ENO1 a compelling therapeutic target. Here, we demonstrate that SU212, a small molecule inhibitor, binds ENO1 and induces its degradation, restricting its intracellular localization. Through these effects, SU212 reduces tumor cell glycolytic activity and glucose uptake and ultimately suppresses tumor growth and metastasis in syngeneic, genetic, and patient-derived xenograft models of triple-negative breast cancer. Further, in a diabetic mouse model, SU212 demonstrated robust anti-tumor efficacy while improving fatty liver conditions and lowering blood glucose. Other glycolytic enzyme inhibitors have been limited by toxicity; thorough p

SUBMITTER: Tailor D 

PROVIDER: S-EPMC12711674 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature