YYSW001 is a potent, highly selective and orally bioavailable JAK1 inhibitor with IC50 of 6 nM, with no activity against JAK2 and JAK3.
YSW001 potently inhibits IL-4-induced STAT6 phosphorylation (JAK1-STAT6, IC50 =0.041 μM) while showing markedly weaker inhibitory potency of GM-CSF-induced STAT5 phosphorylation (JAK2-STAT5 IC50 =5.530 μM) in cellular pathway inhibition assays.
YYSW001 demonstrates superior JAK1/JAK2 selectivity profiles at both enzymatic and cellular levels, markedly outperforming upadacitinib and filgotinib.
YYSW001 exhibits potent inhibitory activity against JAK1 (IC50 = 290.2 nM), with negligible inhibition against JAK2, JAK3, and TYK2 (IC50 > 10000.0 nM) in JAK subtypes in Ba/F3-engineered cell lines.
YYSW001 dose-dependently inhibits STAT3 phosphorylation in both CD3+ T cells and CD14+ monocytes (IC50 = 7065.0 nM and 3001.0 nM) in IL-6-induced STAT3 phosphorylation assays, with minimal inhibitory effects on STAT5 phosphorylation in CD14+ monocytes and CD33+ granulocytes.
YSW001 demonstrates therapeutic efficacy comparable to upadacitinib in rat model of collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models.