GS-143

GS-143 is an inhibitor of IkappaBalpha ubiquitylation. It inhibits ubiquitylation of phosphorylated IkappaBalpha mediated by the SCFbetaTrCP1 E3 ubiquitin ligase complex in vitro (IC50 = 5.2 µM) and reduces TNF-alpha-induced degradation of phosphorylated IkappaBalpha, but not beta-catenin, another SCFbetaTrCP1 substrate, in HeLa S3 cells. GS-143 inhibits LPS-induced expression of TNF-alpha, IL-6, IL-12, ICAM-1, and NF-kappaB in THP-1 cells in a concentration-dependent manner. Intranasal administration of GS-143 (32 µg/animal) reduces the number of eosinophils, lymphocytes, and total cells in bronchoalveolar lavage fluid (BALF) in an ovalbumin-sensitized mouse model of allergic asthma.Formal Name: 4-[4-[[5-(2-fluorophenyl)-2-furanyl]methylene]-4,5-dihydro-5-oxo-3-(phenylmethyl)-1H-pyrazol-1-yl]-benzoic acid. CAS Number: 916232-21-8. Molecular Formula: C28H19FN2O4. Formula Weight: 466.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 25 mg/ml, DMF:PBS (pH 7.2) (1:4): 0.20 mg/ml, DMSO: 10 mg/ml. lambdamax: 288, 420 nm. SMILES: O=C1N(C2=CC=C(C(O)=O)C=C2)N=C(CC3=CC=CC=C3)/C1=C\C4=CC=C(C5=CC=CC=C5F)O4. InChi Code: InChI=1S/C28H19FN2O4/c29-24-9-5-4-8-22(24)26-15-14-21(35-26)17-23-25(16-18-6-2-1-3-7-18)30-31(27(23)32)20-12-10-19(11-13-20)28(33)34/h1-15,17H,16H2,(H,33,34)/b23-17+. InChi Key: IZPMWFSVTDOCDI-HAVVHWLPSA-N.