APY0201 is an inhibitor of FYVE finger-containing phosphoinositide kinase (PIKFYVE; IC50 = 5.2 nM) that selectively inhibits interleukin-12 (IL-12) family inflammatory cytokine production (IC50s = 8, 99, and >10,000 nM for IL-12p70, IL-12p40, and TNF-α in stimulated human peripheral blood mononuclear cells (PBMCs)).1 It is selective for PIKFYVE over a panel of 137 G protein-coupled receptors, enzymes, ion channels, transporters, and other kinases only exhibiting >50% inhibition at lymphocyte-oriented kinase (LOK) and inositol-tetrakisphosphate 1 kinase (ITPK1) at a concentration of 300 nM. APY0201 inhibits Il-12p70 production ex vivo in murine plasma and reduces colonic inflammation in a mouse Il-10-/- cell transfer model of inflammatory bowel disease in a dose-dependent manner.
1.Hayakawa, N., Noguchi, M., Takeshita, A., et al.Structure-activity relationship study, target identification, and pharmacological characterization of a small molecular IL-12/23 inhibitor, APY0201Bioorg. Med. Chem.22(11)3021-3029(2014)