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Despite the introduction and use of newer antifungal agents such as voriconazole,posaconazole and the echinocandins there is an urgent requirement for new classes of antifungals working through novel modes of action.2FG screened a large cbmpound library against Candida albicans and Aspergillus fumigatus and identified several hits with activity against A.fumigatus but not C.albicans.Using medicinal chemistry approaches further analogues were synthesised with improved microbiological potency and ADMET properties.Two lead compounds FG3409 and FG3622 were identified with potent activity against Aspergillus spp,and other filamentous fungi such as Scedosporium spp,Fusarium spp,dermatophyte fungi and the agents of the endemic mycoses.In vivo these compounds display good pharmacokinetics in rodents after intravenous and oral dosing and are able to reduce tissue burdens and prolong survival in murine models of invasive aspergillosis in a dose dependent manner when administered by either route.Preclinical safety studies have been completed for FG3622 and have supported entry to Phase 1 evaluation.Using molecular biology techniques the mode of action and enzyme target of FG3409 and FG3622 has been identified.In summary FG3622 has shown potent in vitro and in vivo antifungal efficacy and preclinical characteristics justifying its clinical evaluation as a potential antifungal therapeutic agent thereby extending the limited treatment options in an area of medical need.