Enolase 2 (ENO2) (ENO2)

Enolase 2 (ENO2), also known as neuron-specific enolase (NSE), is a glycolytic enzyme primarily expressed in mature neurons and neuroendocrine cells (UniProt P09104). It catalyzes the penultimate step of glycolysis, converting 2-phosphoglycerate to phosphoenolpyruvate, and also exhibits "moonlighting" functions such as neurotrophic support and plasminogen binding (Wikipedia, 2024). In oncology, ENO2 is a critical biomarker for small cell lung cancer and neuroblastoma, and it has emerged as a promising therapeutic target through the concept of "collateral lethality" (PubMed, 2020). This strategy involves inhibiting ENO2 in tumors that have lost the redundant ENO1 gene due to chromosomal deletions, thereby selectively starving cancer cells of energy while sparing normal tissues (Nature Metabolism, 2020). Beyond cancer, ENO2 is implicated in neurodegenerative conditions and brain injury, where its release into the serum serves as a marker of neuronal damage (NIH, 2023). Therapeutic development focuses on small-molecule inhibitors like POMHEX and SF2312, though challenges include maintaining isoform specificity and avoiding metabolic toxicity in healthy neural tissues (MedChemExpress, 2024).

Other names

Neuron-specific enolaseNSEGamma-enolasePhosphopyruvate hydratase2-phospho-D-glycerate hydrolaseHEL-S-279

Direct inhibition of enolase enzymatic activity to disrupt the glycolytic pathway, specifically leveraging collateral lethality in ENO1-deleted cancer cells (Nature Metabolism, 2020).