hypothemycin

Hypothemycin is a natural product macrolide and resorcylic acid lactone polyketide originally isolated from fungi such as Hypomyces subiculosus, Setophoma terrestris, and H. tricothecoides[2][3][4]. It exhibits potent anticancer, antifungal, and anti-parasitic activities[2][4]. Mechanistically, hypothemycin acts as a covalent inhibitor of a subset of protein kinases—especially those with a cysteine residue preceding the catalytic DXG motif—including mitogen-activated protein kinase (MAPK/ERK pathway), MEK1/2, ERK1/2, PDGFR, VEGFR2, FLT3, and others[5][7][8]. It inhibits cell survival in various cancer cells (e.g., melanoma and colon cancer), suppresses growth of Trypanosoma brucei (the causative agent of sleeping sickness) in vitro and in vivo mouse models[4][5], disrupts cell wall/endosomal function in certain fungi[4], and suppresses tumor necrosis factor-alpha production by destabilizing TNF-alpha mRNA via inhibition of p38 MAPK and ERK phosphorylation pathways[8]. Hypothemycin has not been approved for clinical use but is used experimentally to probe kinase biology.

Other names

aigialomycin A