C25-140

Cas No.:	1358099-18-9
Chemical Name:	1-(4-Benzylpiperidin-1-yl)-3-[3,5-dimethyl-1-(3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)pyrazol-4-yl]propan-1-one
Synonyms:	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;BCP30323;ZB1522;6-{4-[3-(4-benzylpiperidin-1-yl)-3-oxopropyl]-3,5-dimethyl-1H-pyrazol-1-yl}-3-methyl[1,2,4]triazolo[4,3-b]pyridazine;1-(4-Benzylpiperidin-1-yl)-3-[3,5-dimethyl-1-(3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)pyrazol-;C25-140
SMILES:	O=C(C([H])([H])C([H])([H])C1C(C([H])([H])[H])=NN(C2C([H])=C([H])C3=NN=C(C([H])([H])[H])N3N=2)C=1C([H])([H])[H])N1C([H])([H])C([H])([H])C([H])(C([H])([H])C2C([H])=C([H])C([H])=C([H])C=2[H])C([H])([H])C1([H])[H]
Formula:	C26H31N7O
M.Wt:	457.5706
Purity:	>98%
Sotrage:	2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO

Description:	C25-140, a first-in-class TRAF6-Ubc13 inhibitor, directly binds to TRAF6, thereby blocks the interaction of TRAF6 with Ubc13 and as a consequence lowers TRAF6 activity. C25-140 expands studying the impact of the ubiquitin system on immune signaling and underscores the importance of TRAF6 E3 ligase activity in psoriasis and rheumatoid arthritis (RA)[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 Imiquimod-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]. Animal Model: Imiquimod-induced psoriasis mouse model (male BALB/c mice)[1] Dosage: ~1.5 mg/kg Administration: Topically to the shaved back and the right ear; twice daily for 6 days Result: Showed a dose-dependent improvement of RA disease outcome. Animal Model: Collagen-induced arthritis (CIA) model in DBA1/J mice[1] Dosage: 6 mg/kg, 10 mg/kg, 14 mg/kg Administration: Given i.p.; twice daily for 14 days Result: 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.
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]. Western Blot Analysis[1] Cell Line: TRAF6WT Concentration: 10 μM, 20 μM, 30 μM Incubation Time: 2 hours Result: Effectively reduced TRAF6-mediated ubiquitin chain formation.
References:	[1]. Brenke JK, et al. Targeting TRAF6 E3 ligase activity with a small-molecule inhibitor combats autoimmunity. J Biol Chem. 2018 Aug 24;293(34):13191-13203.