mk-3118 and Mycoses

New classes of synthetic and semi-synthetic β-glucan inhibitors have recently emerged, providing analogs that, in some cases, have been proven to have a high degree of activity against fungi, offering the prospect of alternatives to the commercially available lipopeptide/echinocandin agents caspofungin, micafungin and anidulafungin.. This review covers applications disclosing compound classes that include synthetic pyridazinone analogs, bicyclic heteroaryl ring compounds, aniline derivates, and semi-synthetic echinocandin and enfumafungin derivatives. MK-3118 is an analog of the natural product enfumafungin that, in particular, shows promise as it has a spectrum of activity comparable with caspofungin but has the advantageous property of oral bioavailability.. The diversity of chemical classes in the present review, which have demonstrable activity against β-glucan and the prospect of oral bioavailability, offers hope that safe and effective antifungal drugs will emerge and be commercialized. Of particular note, the Merck compound MK-3118, with solid evidence of efficacy based on preclinical data, has moved into clinical trials.

Topics: Administration, Oral; Animals; Antifungal Agents; beta-Glucans; Biological Availability; Drug Design; Glycosides; Humans; Mycoses; Patents as Topic; Triterpenes

SCY-078, a fungicidal β-1,3-glucan synthesis inhibitor administered as intravenous or oral [

Topics: Animals; Antifungal Agents; Area Under Curve; Aspergillus; Candida; Female; Glycosides; Male; Mycoses; Rats; Rats, Wistar; Tissue Distribution; Triterpenes

Topics: Antifungal Agents; Drug Design; Drug Discovery; Drug Resistance, Fungal; Echinocandins; Glycosides; Humans; Mycoses; Nanoparticles; Triterpenes

The limited armamentarium of active and oral antifungal drugs against emerging non-Aspergillus molds is of particular concern. Current antifungal agents and the new orally available beta-1,3-d-glucan synthase inhibitor SCY-078 were tested in vitro against 135 clinical non-Aspergillus mold isolates. Akin to echinocandins, SCY-078 showed no or poor activity against Mucoromycotina and Fusarium spp. However, SCY-078 was highly active against Paecilomyces variotii and was the only compound displaying some activity against notoriously panresistant Scedosporium prolificans.

Topics: Amphotericin B; Antifungal Agents; Drug Resistance, Fungal; Echinocandins; Fungi; Glucosyltransferases; Glycosides; Humans; Microbial Sensitivity Tests; Mycoses; Retrospective Studies; Triterpenes