Cercosporamide

Cercosporamide is a natural antifungal phytotoxin isolated from the Cercosporidium fungus, which infects the leaves of cassava plants.¹ Its antifungal effect results from its selective and potent inhibition of fungal PKC-like 1 kinases (Pkc1), which are central to cell wall integrity (IC₅₀ = 25 nM for Candida Pkc1).² Cercosporamide less effectively inhibits human PKC isoforms PKCα, β, and γ (IC₅₀s = 1.02, 0.35, and 5.8 μM, respectively), an action linked to lowering of plasma glucose in hyperglycemic mice.^2,3 However, it potently inhibits MAPK-interacting kinases Mnk1 and Mnk2 (IC₅₀ = 115 and 11 nM, respectively), reducing protein translation in cancer cells.^4,5 Cercosporamide is orally bioavailable.^2,3

WARNING This product is not for human or veterinary use.

1. Sugawara, F., Strobel, S., Strobel, G., et al. The structure and biological activity of cercosporamide from Cercosporidium henningsii. The Journal of Organic Chemistry 56(3), 909-910 (1991).

2. Sussman, A., Huss, K., Chio, L.C., et al. Discovery of cercosporamide, a known antifungal natural product, as a selective Pkc1 kinase inhibitor through high-throughput screening. Eukaryot. Cell 3(4), 932-943 (2004).

3. Furukawa, A., Arita, T., Satoh, S., et al. (−)-Cercosporamide derivatives as novel antihyperglycemic agents. Bioorg. Med. Chem. Lett. 19(3), 724-726 (2009).

4. Konicek, B.W., Stephens, J.R., McNulty, A.M., et al. Therapeutic inhibition of MAP kinase interacting kinase blocks eukaryotic initiation factor 4E phosphorylation and suppresses outgrowth of experimental lung metastases. Cancer Res. 71(5), 1849-1857 (2011).

5. Hou, J., Lam, F., Proud, C., et al. Targeting Mnks for cancer therapy. Oncotarget 3(2), 118-131 (2012).