SAICAR is an intermediate of de novo purine nucleotide biosynthesis, activates pyruvate kinase isoform M2 (PKM2) in an isozyme-selective manner (EC50: 0.3 mM).

Upon glucose starvation, cellular SAICAR concentration increases in an oscillatory manner and stimulates PKM2 activity in cancer cells. SAICAR-PKM2 interaction also promotes cancer cell survival in glucose-limited conditions. In glucose-limited conditions, cells with higher SAICAR concentrations (adsl-kd cells or cells overexpressing PAICS) survive better while paics-kd cells died earlier than control-kd cells. SAICAR promotes cancer cell survival in glucose-limited conditions. PKM2-SAICAR phosphorylates and activates Erk1/2, which in turn sensitizes PKM2 for SAICAR binding through phosphorylation. Additionally, PKM2-SAICAR was necessary to induce sustained Erk1/2 activation and mitogen-induced cell proliferation. SAICAR-PKM2 interaction is necessary and sufficient to induce H3 T11 and Erk1/2 phosphorylation [2][3].