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Hypothemycin is a resorcylic acid lactone polyketide originally isolated from H. tricothecoides that has diverse biological activities, including fungicidal, kinase inhibitory, and anticancer properties.[1],[2],[3],[4,][5],[6] It is active against the pathogenic fungi P. litchii, completely inhibiting spore germination when used at a concentration of 0.78 µg/ml.[2] Hypothemycin inhibits MEK (IC50 = 15 nM) and other protein kinases containing a conserved cysteine residue in the ATP-binding domain, including ERK, PDGFR, VEGFR, PKD1, and MAPKAP5/MK5.[3],[4] It also inhibits transforming growth factor β-activated kinase 1 (TAK1) in vitro (IC50 = 33 nM).[5] Hypothemycin inhibits proliferation of cancer cell lines dependent on activating mutations, including A549, MV-4-11, and EOL1 cells (IC50s = 6, 0.006, and 0.0004 µM, respectively) and reduces tumor growth in Ma44 and HCT116 mouse xenograft models when administered at a dose of 25 mg/kg per day.[4],[6]

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