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

ABSTRACT: 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. This pocket was exploited in a virtual screening of a large small-molecule library, identifying two promising candidates, C599 and C998. Both compounds exhibited dose-dependent antiproliferative effects in glioblastoma cell lines and induced apoptosis, as evi

SUBMITTER: Cabrera M 

PROVIDER: S-EPMC11830341 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature