C25-140

C25-140, a first-in-class, orally active, and fairly selective TRAF6-Ubc13 inhibitor, directly binds to TRAF6, and blocks the interaction of TRAF6 with Ubc13. C25-140 lowers TRAF6 activity, reduces NF-κB activation, and combats autoimmunity^[1]. IC50 & Target:TRAF6-Ubc13^[1] In Vitro:C25-140 dose-dependently impedes TRAF6-Ubc13 interaction^[1].
C25-140 (10-30 μM; 2 hours) effectively reduces TRAF6-mediated ubiquitin chain formation^[1].
C25-140 affects TNFα-induced phosphorylation of IκBα as well as NF-κB-induced target gene expression^[1].
C25-140 efficiently inhibits IL-1β- and TNFα-mediated receptor signaling in the context of cytokine activation^[1]. In Vivo:C25-140 (~1.5 mg/kg; topically to the shaved back and the right ear; twice daily for 6 days) ameliorates symptoms of autoimmune psoriasis in R 837-induced psoriasis mouse model^[1].
C25-140 (6-14 mg/kg; given i.p.; twice daily for 14 days) shows a dose-dependent improvement of RA disease outcome in Collagen-induced arthritis (CIA) model^[1].
C25-140 (10 mg/kg; i.v.) treatment shows that the C_max, AUC, t_1/2 and V_d are 9.7 μg/mL, 274083 ng min/mL, 80.62 min, and 4.13 L/kg, respectively^[1].
C25-140 (10 mg/kg; p.o.) treatment shows that the C_max, AUC, t_1/2 and V_d are 3.4 μg/mL, 124034 ng min/mL, 127.33 min and 13.3 L/kg, respectively^[1].
C25-140 (10 mg/kg; i.p.) treatment shows that the C_max, AUC, t_1/2 and V_d are 4.2μg/mL, 100000 ng min/mL, 184 min, 25.6 L/kg, respectively^[1].