(R)-STU104

(R)-STU104 is an inhibitor of the protein-protein interaction between TGF-beta-activated kinase 1 (TAK1) and MAP kinase kinase 3 (MKK3). It binds MKK3 (KD = 71 nM), inhibits the phosphorylation of MKK3 in RAW 264.7 macrophages (IC50 = 4 µM), and disrupts the interaction between MKK3 and TAK1 in the same cells. (R)-STU104 reduces TNF-alpha levels (IC50 = 0.58 µM) and p38 and eukaryotic initiation factor 4E (eIF4E) phosphorylation in LPS-stimulated RAW 264.7 macrophages. It increases body weight and colon length and reduces serum levels of TNF-alpha, IL-1beta, IL-6, and IL-23 in mouse model of ulcerative colitis induced by dextran sulfate (DSS, Cay23250). It also increases the survival rate in an IL-10-/- knockout mouse model of chronic ulcerative colitis.. SMILES: COC1=C2[C@@H](C3=CC=C(C=C3)OC)CC(C2=CC(OC)=C1)=O. InChi Code: InChI=1S/C18H18O4/c1-20-12-6-4-11(5-7-12)14-10-16(19)15-8-13(21-2)9-17(22-3)18(14)15/h4-9,14H,10H2,1-3H3/t14-/m1/s1. InChi Key: OYJBHGSSAJNKJF-CQSZACIVSA-N