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The Antifungal Pipeline: Fosmanogepix, Ibrexafungerp, Olorofim, Opelconazole, and Rezafungin.
Hoenigl, Martin; Sprute, Rosanne; Egger, Matthias; Arastehfar, Amir; Cornely, Oliver A; Krause, Robert; Lass-Flörl, Cornelia; Prattes, Juergen; Spec, Andrej; Thompson, George R; Wiederhold, Nathan; Jenks, Jeffrey D.
  • Hoenigl M; Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria. hoeniglmartin@gmail.com.
  • Sprute R; Division of Infectious Diseases and Global Public Health, Department of Medicine, University of California San Diego, La Jolla, San Diego, CA, USA. hoeniglmartin@gmail.com.
  • Egger M; Clinical and Translational Fungal-Working Group, University of California San Diego, La Jolla, San Diego, CA, USA. hoeniglmartin@gmail.com.
  • Arastehfar A; Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
  • Cornely OA; Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
  • Krause R; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
  • Lass-Flörl C; Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036, Graz, Austria.
  • Prattes J; Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, USA.
  • Spec A; Department I of Internal Medicine, Excellence Center for Medical Mycology (ECMM), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
  • Thompson GR; Chair Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
  • Wiederhold N; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
  • Jenks JD; Clinical Trials Centre Cologne (ZKS Köln), University Hospital Cologne, Faculty of Medicine, University of Cologne, Cologne, Germany.
Drugs ; 81(15): 1703-1729, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1491481
ABSTRACT
The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug-drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available over the last 2 decades, and only one single new agent from a known antifungal class has been approved in the last decade. Nevertheless, there is hope on the horizon, with a number of new antifungal classes in late-stage clinical development. In this review, we describe the mechanisms of drug resistance employed by fungi and extensively discuss the most promising drugs in development, including fosmanogepix (a novel Gwt1 enzyme inhibitor), ibrexafungerp (a first-in-class triterpenoid), olorofim (a novel dihyroorotate dehydrogenase enzyme inhibitor), opelconazole (a novel triazole optimized for inhalation), and rezafungin (an echinocandin designed to be dosed once weekly). We focus on the mechanism of action and pharmacokinetics, as well as the spectrum of activity and stages of clinical development. We also highlight the potential future role of these drugs and unmet needs.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Invasive Fungal Infections / Fungi / Antifungal Agents Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Drugs Year: 2021 Document Type: Article Affiliation country: S40265-021-01611-0

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Invasive Fungal Infections / Fungi / Antifungal Agents Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Drugs Year: 2021 Document Type: Article Affiliation country: S40265-021-01611-0