CADD-based discovery of novel oligomeric modulators of PKM2 with antitumor activity in aggressive human glioblastoma models.

Pyruvate kinase isoform M2 (PKM2) is a multifunctional enzyme capable of transitioning between monomeric, dimeric, and tetrameric states, with its oligomeric equilibrium playing a pivotal role in tumour progression and survival. The unique exon ten at the dimer-dimer interface represents an attractive target for isoform-specific modulation, offering opportunities for disrupting this equilibrium and altering tumour cell dynamics. This study identifies a novel druggable pocket at the PKM2 dimer interface through conformational analysis.