(5Z)-7-Oxozeaenol

(5Z)-7-Oxozeaenol is a resorcylic acid lactone fungal metabolite and an inhibitor of TGF-β activated kinase 1 (TAK1; IC₅₀ = 8.1 nM in the presence of TAK1-binding protein 1 (TAB1)).¹ 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 IκB kinase β (IKKβ) at 300 nM. (5Z)-7-Oxozeaenol inhibits NF-κB 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.^2,3 Topical application of (5Z)-7-oxozeaenol (10 µl of a 1 mg/ml solution) prevents picryl chloride-induced increases in ear thickness in mice.¹

WARNING This product is not for human or veterinary use.

1. Ninomiya-Tsuji, J., Kajino, T., Ono, K., et al. A resorcylic acid lactone, 5Z-7-oxozeaenol, prevents inflammation by inhibiting the catalytic activity of TAK1 MAPK kinase kinase. The Journal of Biological Chemisty 278(20), 18485-18490 (2003).

2. Choo, M.K., Kawasaki, N., Singhirunnusorn, P., et al. Blockade of transforming growth factor-β-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade. Mol. Cancer Ther. 5(12), 2970-2976 (2006).

3. Place, D.E., Samir, P., Malireddi, R.K.S., et al. Integrated stress response restricts macrophage necroptosis. Life Sci. Alliance 5(1), e202101260 (2021).

Place, D.E., Samir, P., Malireddi, R.K.S., et al. Integrated stress response restricts macrophage necroptosis. Life Sci. Alliance 5(1), e202101260 (2021).