Peficitinib hydrochloride, also known as ASP015K, is an orally active JAK inhibitor compound. It exhibits inhibitory activity against JAK1, JAK2, JAK3, and Tyk2, with IC 50 values of 3.9, 5.0, 0.7, and 4.8 nM, respectively.

JAK1:3.9 nM, JAK2:5 nM, Tyk2:4.8 nM, JAK3:0.7 nM

Peficitinib hydrobromide, administered at concentrations ranging from 0 to 100 nM for three days, effectively suppresses IL-2-induced T cell proliferation in a concentration-dependent fashion, with an IC 50 of 10 nM, as demonstrated in a Cell Proliferation Assay using splenocytes from male Lewis rats [1]. Additionally, at concentrations between 10 to 1000 nM, it impedes IL-2-induced STAT5 phosphorylation, displaying a mean IC 50 of 124 nM in rat whole blood and 127 nM in human lymphocytes, indicating its inhibitory action on STAT5 phosphorylation in both rat and human cells [1].

Peficitinib hydrobromide administered orally at doses ranging from 1-30 mg/kg once daily for 24 days demonstrated dose-dependent efficacy in both prophylactic and therapeutic protocols within an adjuvant-induced arthritis (AIA) rat model. Using seven-week-old female Lewis rats, the study quantitatively assessed the compound’s impact on disease markers: it significantly reduced paw volume starting at 1 mg/kg, with an ED50 of 2.7 mg/kg (95% confidence interval: 1.5–4.2 mg/kg), and notably decreased bone destruction scores at doses of 10 mg/kg or higher. At the maximum dose of 30 mg/kg, peficitinib hydrobromide effectively mitigated both paw swelling and bone damage, showcasing substantial therapeutic potential in the AIA model.