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Here we show that FR171456 specifically targets the sterol-4-alpha-carboxylate-3-dehydrogenase (S<jats:italic>accharomyces cerevisiae<\/jats:italic>\u2014Erg26p, <jats:italic>Homo sapiens<\/jats:italic>\u2014NSDHL (NAD(P) dependent steroid dehydrogenase-like)), an essential enzyme in the ergosterol\/cholesterol biosynthesis pathway. FR171456 significantly alters the levels of cholesterol pathway intermediates in human and yeast cells. Genome-wide yeast haploinsufficiency profiling experiments highlight the <jats:italic>erg26\/ERG26<\/jats:italic> strain, and multiple mutations in <jats:italic>ERG26<\/jats:italic> confer resistance to FR171456 in growth and enzyme assays. Some of these <jats:italic>ERG26<\/jats:italic> mutations likely alter Erg26 binding to FR171456, based on a model of Erg26. Finally, we show that FR171456 inhibits an artificial Hepatitis C viral replicon, and has broad antifungal activity, suggesting potential additional utility as an anti-infective. 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