Antifungal drug discovery and development--fourth international summit. 10-11 March 1999, Princeton, New Jersey, USA.
Genetic and genomic approaches to discovery, selection and evaluation of antifungal targets were extensively discussed by several speakers at this meeting. Experimental targets with early lead compounds available from screening programs include translation (Ribogene Inc), transcription (SCRIPTGEN Pharmaceuticals Inc), and protein geranylgeranylation (Mitotix Inc). Classes of compounds which are more advanced in preclinical evaluation include the sordarins, inhibitors of fungal elongation factor 2 under development by Glaxo Wellcome plc and Merck and Co Inc, and a series of fungicidal peptides originally derived from a domain of the human neutrophil bactericidal permeability-increasing protein (BPI, Xoma Ltd). Preclinical and early clinical data were presented for two compounds: caspofungin (MK-0991, Merck and Co Inc), an echinocandin with a broad-spectrum of activity for parenteral application, and Sch-56592 (Schering-Plough Corp), an orally active triazole. The oral antimycotic, terbinafine (Novartis AG), primarily used in dermatological infections, shows potent synergy with azoles and has potential applications against several serious and drug-resistant fungal pathogens. Amphotericin B, which has long been the gold standard for therapy of life-threatening infections, is now available in several liposomal formulations, including AmBisome (Fujisawa Pharmaceutical Co Ltd) and Abelcet (The Liposome Company Inc) which show a reduced incidence of adverse events.
Ryder
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Novartis Research Institute, Brunner Strasse 59, A-1235 Vienna, Austria. neil.ryder@pharma.Novartis.com