TNF-α-IN-2 is a highly potent and orally bioavailable inhibitor of tumor necrosis factor alpha (TNFα), exhibiting an IC50 of 25 nM in the HTRF assay. It exerts its inhibitory effects by inducing conformational changes in the TNFα trimer upon binding, resulting in disrupted signaling when the trimer interacts with TNFR1. TNF-α-IN-2 holds promise as a valuable tool for investigating the pathogenesis of rheumatoid arthritis[1].

TNF-α:25 nM (IC50)

TNF-α-IN-2 (compound 42) (30 min) inhibits the E-selectin expression induced by soluble TNFα in HUVECs, with an IC50 of 30 nM[1].

TNF-α-IN-2 (5-25 mg/kg; p.o. 1 h before TNF stimulation) inhibits TNF-induced IL-6 in mice[1].TNF-α-IN-2 (2-10 mg/kg; p.o. twice daily for 10 d) dose dependently reduces both the clinical score as well as the levels of inflammatory cytokines and leukocyte cell surface receptors in mice[1].TNF-α-IN-2 (0.5 mg/kg; i.v.) exhibits long t1/2 (6.2 h), low CL (6.6 mL/min?kg), and Vss (3.2 L/kg) in mice[1].TNF-α-IN-2 (2 mg/kg; p.o.) exhibits good oral bioavailability (58%), Cmax (0.47 μM), and AUCtot (5.9 μM?h) in mice[1].