C25-140

C25-140 is an inhibitor of the protein-protein interaction between the E3 ligase TNF receptor-associated factor 6 (TRAF6) and ubiquitin-conjugating enzyme E2 N (Ubc13, IC50 = 2.6 µM). It selectively inhibits the TRAF6-Ubc13 interaction over the interactions between Ubc13-OTUB1 and Ubc13-Uev1a. C25-140 (30 µM) also selectively inhibits TRAF6-dependent ubiquitination over a panel of various E3 ligase/E2 enzymes, but does inhibit cellular inhibitor of apoptosis 1 (cIAP1) and E1/E2 enzymes in cell-free assays. It reduces IL-1beta-induced activation of NF-kappaB in mouse embryonic fibroblasts (MEFs) when used at a concentration of 50 µM. Topical application of C25-140 (~1.5 mg/kg twice per day) reduces scaling and erythema in a mouse model of psoriasis induced by the TLR7 agonist imiquimod (Cay-14956). It decreases disease severity in a mouse model of collagen-induced arthritis when administered at doses ranging from 6 to 14 mg/kg twice per day. C25-140 (5 mg/kg) also reduces alveolar septal thickening, pulmonary edema, and inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) in a mouse model of lung injury induced by mechanical ventilation with high tidal volumes.Formal Name: 3-[3,5-dimethyl-1-(3-methyl-1,2,4-triazolo[4,3-b]pyridazin-6-yl)-1H-pyrazol-4-yl]-1-[4-(phenylmethyl)-1-piperidinyl]-1-propanone. CAS Number: 1358099-18-9. Molecular Formula: C26H31N7O. Formula Weight: 457.6. Purity: >98%. Formulation: (Request formulation change), A solid. Solubility: DMSO: Soluble, Methanol: Soluble. SMILES: O=C(CCC1=C(C)N(C(C=C2)=NN3C2=NN=C3C)N=C1C)N4CCC(CC4)CC5=CC=CC=C5. InChi Code: InChI=1S/C26H31N7O/c1-18-23(19(2)32(29-18)25-11-10-24-28-27-20(3)33(24)30-25)9-12-26(34)31-15-13-22(14-16-31)17-21-7-5-4-6-8-21/h4-8,10-11,22H,9,12-17H2,1-3H3. InChi Key: HFKVRXVHZGBRKF-UHFFFAOYSA-N.