INDY is an ATP-competitive inhibitor of dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A (DYRK1A; Ki = 180 nM; IC50 = 240 nM). It is selective for DYRK1A over monoamine oxidase (MAO) A and B at concentrations up to 100 μM. INDY inhibits DYRK1A phosphorylation of tau in COS-7 cells expressing EGFP-DYRK1A and EGFP-tau in a concentration-dependent manner. It also restores signaling through nuclear factory of activated T cells (NFAT) and NFAT-dependent transcription in HEK293 cells overexpressing DYRK1A. In vivo, INDY reverses developmental deformities induced by DYRK1A overexpression in X. laevis embryos. INDY also induces proliferation of human and rat β-cells and increases insulin secretion by human islets in vitro.
