DASA-58 is a selective activator of pyruvate kinase M2 (PKM2; AC50 = 38 nM in vitro, EC50 = 19.6 μM in cells). DASA-58 converts PKM2 to a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins. Through its effects on PKM2, DASA-58 blocks the induction of HIF-1α by lipopolysaccharide in bone marrow-derived macrophages, suppressing the expression of several HIF-1α-dependent targets, including IL-1β. It also impairs metastatic dissemination of prostate cancer PCa cells in SCID mice.
