APY0201

APY0201 is a potent PIKfyve inhibitor, which inhibits the conversion of PtdIns3P to PtdIns(3,5)P₂ in the presence of in the presence of [³³P]ATP with an IC₅₀ of 5.2 nM. APY0201 also inhibits IL-12/IL-23 production. IC50 & Target: IC50: 5.2 nM (PIKfyve), 8.4 nM (IL-12p70, in mouse TG-PEC and human PBMC), 16 nM (IL-12p40, in mouse TG-PEC)^[1] In Vitro: APY0201 works differently from anti-IL-12/23 antibodies and acts by inhibiting production of these proinflammatory cytokines with characteristic selectivity over other cytokines, including tumor necrosis factor-alpha (TNF-α). In stimulated thioglycollate-induced mouse peritoneal exudate cells (TG-PEC), APY0201 strongly inhibits IL-12p70 and IL-12p40 production, with IC₅₀s of 8.4 and 16 nM, respectively. APY0201 also inhibits IL-12p40 at 99 nM in human PBMC. APY0201 shows significant selectivity for the production of IL-12p70 and IL-12p40 over TNF-α, and this selectivity is maintained across species^[1]. In Vivo: Oral APY0201 at a 30 mg/kg dose shows significant reduction of IL-12p70 production (78% inhibition relative to that of the vehicle control), which implys that the inhibitory potential of APY0201 against IL-12 is confirmed in the animal experiment^[1].