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1-aminobenzotriazole

  • 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
    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
    APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental <em>Coccidioides immitis</em> Pneumonia
    Experimental Therapeutics
    APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental Coccidioides immitis Pneumonia

    Coccidioidomycosis is a systemic fungal infection caused by the inhalation of the arthroconidia of either of two closely related dimorphic fungi, Coccidioides immitis and C. posadasii, that are endemic in the southwestern United States and other areas in the Western Hemisphere. Chronic cavitary...

    Suganya Viriyakosol, Mili Kapoor, Sharon Okamoto, Jonathan Covel, Quinlyn A. Soltow, Michael Trzoss, Karen Joy Shaw, Joshua Fierer
  • Open Access
    APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis
    Experimental Therapeutics
    APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis

    Invasive pulmonary aspergillosis (IPA) due to Aspergillus fumigatus is a serious fungal infection in the immunosuppressed patient population. Despite the introduction of new antifungal agents, mortality rates remain high, and new treatments are needed.

    Teclegiorgis Gebremariam, Sondus Alkhazraji, Abdullah Alqarihi, Heewon H. Jeon, Yiyou Gu, Mili Kapoor, Karen J. Shaw, Ashraf S. Ibrahim
  • Open Access
    Significantly Improved Pharmacokinetics Enhances <em>In Vivo</em> Efficacy of APX001 against Echinocandin- and Multidrug-Resistant <span class="named-content genus-species" id="named-content-1">Candida</span> Isolates in a Mouse Model of Invasive Candidiasis
    Experimental Therapeutics
    Significantly Improved Pharmacokinetics Enhances In Vivo Efficacy of APX001 against Echinocandin- and Multidrug-Resistant Candida Isolates in a Mouse Model of Invasive Candidiasis

    APX001 is a first-in-class, intravenous and orally available, broad-spectrum antifungal agent in clinical development for the treatment of life-threatening invasive fungal infections. The half-life of APX001A, the active moiety of APX001, is significantly shorter in mice than in humans (1.4 to 2.75 h in mice versus 2 to 2.5 days in humans), making the exploration of efficacy in mouse models difficult.

    Yanan Zhao, Min Hee Lee, Padmaja Paderu, Annie Lee, Cristina Jimenez-Ortigosa, Steven Park, Robert S. Mansbach, Karen Joy Shaw, David S. Perlin
  • Open Access
    Experimental Therapeutics
    In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus

    Cryptococcal meningitis (CM), caused primarily by Cryptococcus neoformans, is uniformly fatal if not treated. Treatment options are limited, especially in resource-poor geographical regions, and mortality rates remain high despite current therapies.

    Karen Joy Shaw, Wiley A. Schell, Jonathan Covel, Gisele Duboc, C. Giamberardino, Mili Kapoor, Molly Moloney, Quinlyn A. Soltow, Jennifer L. Tenor, Dena L. Toffaletti, Michael Trzoss, Peter Webb, John R. Perfect
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