Peficitinib hydrobromide

Peficitinib (ASP015K) hydrobromide is an orally active JAK inhibitor, with IC50s of 3.9, 5.0, 0.7 and 4.8 nM for JAK1, JAK2, JAK3 and Tyk2, respectively.

Signaling Pathways >> JAK/STAT Signaling >> JAK

Signaling Pathways >> Epigenetics >> JAK

Signaling Pathways >> Stem Cell/Wnt >> JAK

Research Areas >> Inflammation/Immunology

JAK3:0.7 nM (IC50)

JAK1:3.9 nM (IC50)

JAK2:5 nM (IC50)

Tyk2:4.8 nM (IC50)

Peficitinib hydrobromide (0-100 nM; 3 days) inhibits IL-2-induced T cell proliferation in a concentration-dependent manner[1]. Peficitinib hydrobromide (10-1000 nM) inhibits IL-2-induced STAT5 phosphorylation in a concentration-dependent manner with a mean IC50 of 124 nM in rat whole blood, and inhibits STAT5 phosphorylation with a mean IC50 of 127 nM in human lymphocytes[1]. Cell Proliferation Assay[1] Cell Line: Splenocytes from male Lewis rats Concentration: 0-100 nM Incubation Time: 3 days Result: Inhibited IL-2-induced T cell proliferation in a concentration-dependent manner with an IC50 of 10 nM.

Peficitinib hydrobromide (1-30 mg/kg; p.o.; once daily for 24 days) shows dose-dependent efficacy both in prophylactic and therapeutic dosing regimens in an adjuvant-induced arthritis rat model[1]. Animal Model: Seven-weeks-old female Lewis rats, adjuvant-induced arthritis (AIA) model[1] Dosage: 1, 3, 10, and 30 mg/kg Administration: Oral administration, once daily for 24 days Result: Significantly inhibited the increase in paw volume at doses of 1 mg/kg or greater with an ED50 value of 2.7 mg/kg (95% confidence interval: 1.5–4.2 mg/kg). Significantly reduced the bone destruction score at 10 mg/kg or greater and almost fully ameliorated both paw swelling and bone destruction scores at 30 mg/kg.

[1]. Ito M, et al. A novel JAK inhibitor, peficitinib, demonstrates potent efficacy in a rat adjuvant-induced arthritis model. J Pharmacol Sci. 2017 Jan;133(1):25-33.