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fosmanogepix

  • <em>In Vitro</em> Activity of Manogepix against Multidrug-Resistant and Panresistant <span class="named-content genus-species" id="named-content-1">Candida auris</span> from the New York Outbreak
    Susceptibility
    In Vitro Activity of Manogepix against Multidrug-Resistant and Panresistant Candida auris from the New York Outbreak

    An ongoing Candida auris outbreak in the New York metropolitan area is the largest recorded to date in North America. Laboratory surveillance revealed NY C. auris isolates are resistant to fluconazole, with variable resistance to other currently used broad-spectrum antifungal drugs, and that several...

    YanChun Zhu, Shannon Kilburn, Mili Kapoor, Sudha Chaturvedi, Karen Joy Shaw, Vishnu Chaturvedi
  • Manogepix (APX001A) <em>In Vitro</em> Activity against <span class="named-content genus-species" id="named-content-1">Candida auris</span>: Head-to-Head Comparison of EUCAST and CLSI MICs
    Susceptibility
    Manogepix (APX001A) In Vitro Activity against Candida auris: Head-to-Head Comparison of EUCAST and CLSI MICs

    Fosmanogepix is a novel prodrug in a new class of antifungal agents. Manogepix is the active moiety. We evaluated the CLSI and EUCAST MICs of manogepix and eight comparators against Candida auris. CLSI M27-A3 susceptibility testing of manogepix was performed for 122 C. auris isolates and compared to...

    Maiken Cavling Arendrup, Anuradha Chowdhary, Karin Meinike Jørgensen, Joseph Meletiadis
  • <em>In Vitro</em> Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC Determination
    Editor's Pick Susceptibility
    In Vitro Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC Determination

    Manogepix (APX001A) is the active moiety of the drug candidate fosmanogepix (APX001), currently in clinical development for the treatment of invasive fungal infections. We compared manogepix EUCAST minimum effective concentrations (MECs) to MICs of five comparators and CLSI MECs and MICs by a colorimetric method against contemporary molds. EUCAST susceptibility testing was performed for 161 isolates. Interlaboratory and intermethod...

    Karin Meinike Jørgensen, Karen M. T. Astvad, Maiken Cavling Arendrup
  • Open Access
    Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to <span class="named-content genus-species" id="named-content-1">Rhizopus arrhizus</span>
    Experimental Therapeutics
    Fosmanogepix (APX001) Is Effective in the Treatment of Pulmonary Murine Mucormycosis Due to Rhizopus arrhizus

    Mucormycosis is a life-threatening infection with high mortality that occurs predominantly in immunocompromised patients. Manogepix (MGX) is a novel antifungal that targets Gwt1, a protein involved in an early step in the conserved glycosylphosphotidyl inositol (GPI) posttranslational modification pathway of surface proteins in eukaryotic cells. Inhibition of fungal inositol acylation by MGX results in pleiotropic effects, including...

    Teclegiorgis Gebremariam, Sondus Alkhazraji, Abdullah Alqarihi, Nathan P. Wiederhold, Karen Joy Shaw, Thomas F. Patterson, Scott G. Filler, Ashraf S. Ibrahim
  • Open Access
    Enhanced Efflux Pump Expression in <em>Candida</em> Mutants Results in Decreased Manogepix Susceptibility
    Mechanisms of Resistance
    Enhanced Efflux Pump Expression in Candida Mutants Results in Decreased Manogepix Susceptibility

    Manogepix is a broad-spectrum antifungal agent that inhibits glycosylphosphatidylinositol (GPI) anchor biosynthesis. Using whole-genome sequencing, we characterized two efflux-mediated mechanisms in the fungal pathogens Candida albicans and Candida parapsilosis that resulted in decreased manogepix...

    Sean D. Liston, Luke Whitesell, Mili Kapoor, Karen Joy Shaw, Leah E. Cowen
  • Open Access
    Fosmanogepix (APX001) Is Effective in the Treatment of Immunocompromised Mice Infected with Invasive Pulmonary Scedosporiosis or Disseminated Fusariosis
    Editor's Pick Experimental Therapeutics
    Fosmanogepix (APX001) Is Effective in the Treatment of Immunocompromised Mice Infected with Invasive Pulmonary Scedosporiosis or Disseminated Fusariosis

    There are limited treatment options for immunosuppressed patients with lethal invasive fungal infections due to Fusarium and Scedosporium. Manogepix (MGX; APX001A) is a novel antifungal that targets the conserved Gwt1 enzyme required for localization of glycosylphosphatidylinositol-anchored mannoproteins in fungi. We evaluated the in vitro activity of MGX and the efficacy of the prodrug fosmanogepix (APX001)...

    Sondus Alkhazraji, Teclegiorgis Gebremariam, Abdullah Alqarihi, Yiyou Gu, Zeinab Mamouei, Shakti Singh, Nathan P. Wiederhold, Karen J. Shaw, Ashraf S. Ibrahim
  • Open Access
    Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis
    Experimental Therapeutics
    Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

    Galactomannan (GM) detection in biological samples has been shown to predict therapeutic response by azoles and polyenes. In a murine invasive pulmonary aspergillosis model, fosmanogepix or posaconazole treatment resulted in an ∼6- to 7-log reduction in conidial equivalents (CE)/g lung tissue after 96 h versus placebo.

    Teclegiorgis Gebremariam, Sondus Alkhazraji, Yiyou Gu, Shakti Singh, Abdullah Alqarihi, Karen Joy Shaw, Ashraf S. Ibrahim
  • Open Access
    Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) in <em>Candida</em> Species
    Mechanisms of Resistance
    Evaluation of Resistance Development to the Gwt1 Inhibitor Manogepix (APX001A) in Candida Species

    Manogepix (MGX) targets the conserved fungal Gwt1 enzyme required for acylation of inositol early in the glycosylphosphatidylinositol biosynthesis pathway. The prodrug fosmanogepix is currently in clinical development for the treatment of invasive fungal infections.

    Mili Kapoor, Molly Moloney, Quinlyn A. Soltow, Chris M. Pillar, Karen Joy Shaw
  • Open Access
    Efficacy of Delayed Therapy with Fosmanogepix (APX001) in a Murine Model of <span class="named-content genus-species" id="named-content-1">Candida auris</span> Invasive Candidiasis
    Experimental Therapeutics
    Efficacy of Delayed Therapy with Fosmanogepix (APX001) in a Murine Model of Candida auris Invasive Candidiasis

    The emerging pathogenic yeast Candida auris is associated with antifungal resistance and high mortality. The novel antifungal agent manogepix (APX001A) inhibits glycosylphosphatidylinositol-anchored protein maturation and has demonstrated activity against numerous pathogenic fungi, including C. auris...

    Nathan P. Wiederhold, Laura K. Najvar, Karen J. Shaw, Rosie Jaramillo, Hoja Patterson, Marcos Olivo, Gabriel Catano, Thomas F. Patterson
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