An integrated approach for identification and target validation of antifungal compounds active against Erg11p.

ABSTRACT: Systemic life-threatening fungal infections represent a significant unmet medical need. Cell-based, phenotypic screening can be an effective means of discovering potential novel antifungal compounds, but it does not address target identification, normally required for compound optimization by medicinal chemistry. Here, we demonstrate a combination of screening, genetic, and biochemical approaches to identify and characterize novel antifungal compounds. We isolated a set of novel non-azole antifungal compounds for which no target or mechanism of action is known, using a screen for inhibition of Saccharomyces cerevisiae proliferation. Haploinsufficiency profiling of these compounds in S. cerevisiae suggests that they target Erg11p, a cytochrome P450 family member, which is the target of azol

SUBMITTER: Hoepfner D 

PROVIDER: S-EPMC3421618 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature