(5Z)-7-Oxozeaenol

(5Z)-7-Oxozeaenol is a resorcylic acid lactone fungal metabolite and an inhibitor of TGF-beta activated kinase 1 (TAK1, IC50 = 8.1 nM in the presence of TAK1-binding protein 1 (TAB1)). It is selective for TAK1 over MEK1 and MEKK1 (IC50s = 411 and 268 nM, respectively), as well as apoptosis signal-regulating kinase 1 (ASK1) and IkappaB kinase beta (IKKbeta) at 300 nM. (5Z)-7-Oxozeaenol inhibits NF-kappaB activity in a reporter assay using HEK293 cells expressing TAK1 and TAB1 (IC50 = 83 nM) and reduces IL-1-induced increases in COX-2 levels in mouse embryonic fibroblasts (MEFs). It sensitizes HeLa cells to apoptosis induced by TNF-related apoptosis-inducing ligand (TRAIL) when used at a concentration of 300 nM and induces necroptosis when used in combination with TNF and zVAD in primary mouse bone marrow-derived macrophages (BMDMs) at 100 nM. Topical application of (5Z)-7-oxozeaenol (10 µl of a 1 mg/ml solution) prevents picryl chloride-induced increases in ear thickness in mice.Formal Name: (3S,5Z,8S,9S,11E)-3,4,9,10-tetrahydro-8,9,16-trihydroxy-14-methoxy-3-methyl-1H-2-benzoxacyclotetradecin-1,7(8H)-dione. CAS Number: 253863-19-3. Synonyms: FR148083, L-783,279, LL-Z 1640-2. Molecular Formula: C19H22O7. Formula Weight: 362.4. Purity: >99%. Formulation: (Request formulation change), A solid. Solubility: DMF: 30 mg/ml, DMSO: 30 mg/ml, DMSO:PBS (pH 7.2) (1:20): 50 µg/ml, Ethanol: 1 mg/ml. lambdamax: 232, 273, 317 nm. SMILES: O=C1[C@@H](O)[C@@H](O)C/C=C/C2=CC(OC)=CC(O)=C2C(O[C@@H](C)C/C=C\1)=O. InChi Code: InChI=1S/C19H22O7/c1-11-5-3-7-14(20)18(23)15(21)8-4-6-12-9-13(25-2)10-16(22)17(12)19(24)26-11/h3-4,6-7,9-11,15,18,21-23H,5,8H2,1-2H3/b6-4+,7-3-/t11-,15-,18+/m0/s1. InChi Key: NEQZWEXWOFPKOT-BYRRXHGESA-N. Origin: Fungus/Curvularia sp..