Next generation thiazolyl ketone inhibitors of cytosolic phospholipase A₂ α for targeted cancer therapy.

ABSTRACT: Eicosanoids are key players in inflammatory diseases and cancer. Targeting their production by inhibiting Group IVA cytosolic phospholipase A₂ (cPLA₂α) offers a promising approach for cancer therapy. In this study, we synthesize a second generation of thiazolyl ketone inhibitors of cPLA₂α starting with compound GK470 (AVX235) and test their in vitro and cellular activities. We identify a more potent and selective lead molecule, GK420 (AVX420), which we test in parallel with AVX235 and a structurally unrelated compound, AVX002 for inhibition of cell viability across a panel of cancer cell lines. From this, we show that activity of polycomb group repressive complex 2 is a key molecular determinant of sensitivity to cPLA₂α inhibition, while resistan

SUBMITTER: Ashcroft FJ 

PROVIDER: S-EPMC11696576 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature