PF-1163A is a depsipeptide antifungal isolated from Penicillium that inhibits ergosterol synthesis (IC50 = 12 ng/ml). In S. cerevisiae transfected with ERG biosynthesis genes, PF-1163 inhibits ERG25p, a C-4 methyl oxidase in the ERG biosynthetic pathway, with a MIC value of 12.5 µg/ml, while a strain overexpressing ERG25p is resistant. It inhibits growth of C. albicans (MIC = 8 µg/ml) but not of other Candida strains, A. fumigatus, or HepG2 cells. It also acts synergistically with fluconazole to reduce growth of azole-resistant C. albicans (MICs = 1 and 0.0078 µg/ml alone and in combination, respectively). PF-1163A is a more polar form of PF-1163B .