Blovacitinib (TUL01101) is a potent, selective and oral Janus kinase 1 (JAK1) inhibitor with IC50 of 3 nM, >12-fold selectivity for JAK2 and TYK2. TUL01101 interacts with JAK1 JH1 domain. TUL01101 can effectively inhibit signaling pathways involved by JAK1 mediated by IL-6, with stronger inhibitory activity than filgotinib (IC50: 125.9 vs 407.4 nM). TUL01101 can effectively inhibit JAK1-JAK3 signaling pathway mediated by IL-2 and JAK1-TYK2 signaling pathway mediated by IFNα. TUL01101 does not inhibit JAK2 signaling pathways induced by GM-CSF. TUL01101 (1 mg/kg, BID, p.o.) exhibited effective activity in the treatment of RA both in collagen-induced arthritis (CIA) and adjuvant-induced arthritis (AIA) models, with low dose and low toxicity.
