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 induces conformational changes in the TNFα trimer upon binding, disrupting 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), when administered for 30 minutes, effectively suppresses soluble TNFα-induced E-selectin expression in HUVECs, demonstrating an inhibitory concentration (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. TNF-α-IN-2 (2-10 mg/kg; p.o. twice daily for 10 d) dose-dependently reduces both the clinical score and levels of inflammatory cytokines and leukocyte cell surface receptors in mice. TNF-α-IN-2 (0.5 mg/kg; i.v.) exhibits a l ng t1/2 (6.2 h), low CL (6.6 6.6 mL/min•kg), and Vss (3.2 L/kg) in mice. TNF-α-IN-2 (2 mg/kg; p.o.) displays good oral bioavailability (58%), Cmax (0.47 μM), and AUCtot (5.9 μM•h) in mice.