DASA-58

DASA-58 is a selective activator of pyruvate kinase M2 (PKM2; AC₅₀ = 38 nM in vitro, EC₅₀ = 19.6 µM in cells).¹ DASA-58 converts PKM2 to a constitutively active enzyme state that is resistant to inhibition by tyrosine-phosphorylated proteins.¹ 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.² It also impairs metastatic dissemination of prostate cancer PCa cells in SCID mice.³

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1. Anastasiou, D., Yu, Y., Israelsen, W.J., et al. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat. Chem. Biol. 8(10), 839-847 (2012).

2. Palsson-McDermott, E.M., Curtis, A.M., Goel, G., et al. Pyruvate kinase M2 regulates Hif-1α activity and IL-1β induction and is a critical determinant of the warburg effect in LPS-activated macrophages. Cell. Metab. 21(1), 65-80 (2015).

3. Giannoni, E., Taddei, M.L., Morandi, A., et al. Targeting stromal-induced pyruvate kinase M2 nuclear translocation impairs oxphos and prostate cancer metastatic spread. Oncotarget 6(27), 24061-24074 (2015).