C25-140

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

C25-140 是 TRAF6-Ubc13 相互作用的特异性首创小分子抑制剂，可结合 TRAF6。

C25-140 is a specific, first-in-class small molecule inhibitor of the TRAF6-Ubc13 interaction, binds TRAF6, inhibits TRAF6-Ubc13 interaction and TRAF6 activity; C25-140 effectively reduced TRAF6-mediated ubiquitin chain formation in vitro, impedes NF-κB activation in various immune and inflammatory signaling pathways also in primary human and murine cells; does not effect other E3 ligases (MDM2, TRIM63, ITCH, E6AP and RNF4), also does inhibit E1/E2 reactions.

C25-140 dose-dependently impedes TRAF6-Ubc13 interaction.C25-140 (10-30 μM; 2 hours) effectively reduces TRAF6-mediated ubiquitin chain formation.C25-140 affects TNFα-induced phosphorylation of IκBα as well as NF-κB-induced target gene expression.C25-140 efficiently inhibits IL-1β- and TNFα-mediated receptor signaling in the context of cytokine activation. Western Blot Analysis Cell Line:TRAF6WT Concentration:10 μM, 20 μM, 30 μMIncubation Time:2 hours Result:Effectively reduced TRAF6-mediated ubiquitin chain formation.

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.?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.C25-140 (10 mg/kg; i.v.) treatment shows that the Cmax, AUC, t1/2 and Vd are 9.7 μg/mL, 274083 ng min/mL, 80.62 min, and 4.13 L/kg, respectively..?C25-140 (10 mg/kg; p.o.) treatment shows that the Cmax, AUC, t1/2 and Vd are 3.4 μg/mL, 124034 ng min/mL, 127.33 min and 13.3 L/kg, respectively.C25-140 (10 mg/kg; i.p.) treatment shows that the Cmax, AUC, t1/2 and Vd are 4.2μg/mL, 100000 ng min/mL, 184 min, 25.6 L/kg, respectively. Animal Model:R 837-induced psoriasis mouse model (male BALB/c mice)Dosage:~1.5 mg/kg Administration:Topically to the shaved back and the right ear; twice daily for 6 daysResult:Showed a dose-dependent improvement of RA disease outcome.Animal Model:Collagen-induced arthritis (CIA) model in DBA1/J miceDosage:6 mg/kg, 10 mg/kg, 14 mg/kg Administration:Given i.p.; twice daily for 14 daysResult:Ameliorated the arthritic index to almost baseline levels in this efficacy model at doses of 10 and 14 mg/kg. Dose-dependently improved symptoms of RA including inflammation and structural damage.Animal Model:BALB/C miceDosage:10 mg/kg Administration:I.v. (Pharmacokinetic Analysis)Result:The Cmax, AUC, t1/2 and Vd were 9.7 μg/mL, 274083 ng min/mL, 80.62 min, and 4.13 L/kg, respectively.

TRAF6-Ubc13 inhibitor C25-140

Proteasome/Ubiquitin

E2

E2

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1358099-18-9

457.582

C26H31N7O

>98% (HPLC)

DMSO : ≥ 130 mg/mL 284.11 mM

O=C(N1CCC(CC2=CC=CC=C2)CC1)CCC3=C(C)N(C4=NN5C(C=C4)=NN=C5C)N=C3C

1-(4-benzylpiperidin-1-yl)-3-(3,5-dimethyl-1-(3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazol-4-yl)propan-1-one

(-20℃)

With Ice Pack

≥ 2 years