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

Viriyakosol, Suganya; Kapoor, Mili; Okamoto, Sharon; Covel, Jonathan A.; Soltow, Quinlyn A.; Trzoss, Michael; Shaw, Karen Joy; Fierer, Joshua

doi:10.1128/aac.01715-18

Cited by 43 publications

(29 citation statements)

References 33 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, when higher ABT concentrations were evaluated (up to 250 g/ml), no antifungal activity was observed (7). Concordant with the lack of in vitro activity, ABT treatment alone did not enhance survival time nor reduce tissue fungal burden compared with infected mice without treatment in several animal models, including IPA (7), cryptococcal meningitis (8), or Coccidioides immitis pneumo-nia (9). Therefore, the survival benefit seen in mice receiving fosmanogepixϩABT is solely due to the effect of MGX.…”

mentioning

confidence: 86%

Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

Gebremariam¹,

Alkhazraji²,

Gu³

et al. 2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

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. Changes in GM levels in BAL fluid and serum mirrored reductions in lung CE, with significant decreases seen after 96 h or 72 h for fosmanogepix or posaconazole, respectively (P < 0.02).

show abstract

mentioning

confidence: 86%

Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

Gebremariam¹,

Alkhazraji²,

Gu³

et al. 2019

Antimicrob Agents Chemother

Self Cite

View full text Add to dashboard Cite

show abstract

“…It targets the fungal-specific enzyme Gwt1, responsible for an early step in glycosylphosphatidylinositol (GPI)-anchor biosynthesis (Figure 1) [38]. This agent has demonstrated potency against multiple yeasts, moulds, and endemic mycoses [39]. Low MICs have been reported for Candida spp.…”

Section: Fosmanogepix (Apx001)mentioning

confidence: 99%

Aspiring Antifungals: Review of Current Antifungal Pipeline Developments

Gintjee

Donnelley

Thompson

2020

JoF

156

161

View full text Add to dashboard Cite

Invasive fungal infections are associated with significant morbidity and mortality, and their management is restricted to a variety of agents from five established classes of antifungal medication. In practice, existing antifungal agents are often constrained by dose-limiting toxicities, drug interactions, and the routes of administration. An increasing prevalence of invasive fungal infections along with rising rates of resistance and the practical limitations of existing agents has created a demand for the development of new antifungals, particularly those with novel mechanisms of action. This article reviews antifungal agents currently in various stages of clinical development. New additions to existing antifungal classes will be discussed, including SUBA-itraconazole, a highly bioavailable azole, and amphotericin B cochleate, an oral amphotericin formulation, as well as rezafungin, a long-acting echinocandin capable of once-weekly administration. Additionally, novel first-in-class agents such as ibrexafungerp, an oral glucan synthase inhibitor with activity against various resistant fungal isolates, and olorofim, a pyrimidine synthesis inhibitor with a broad spectrum of activity and oral formulation, will be reviewed. Various other innovative antifungal agents and classes, including MGCD290, tetrazoles, and fosmanogepix, will also be examined.

show abstract

“…Arthroconidia are the infectious propagules of Coccidioides. Infection of murine models through intranasal delivery is the preferred and widely used method to understand Coccidioides pathology (Campuzano et al, 2020;Castro-Lopez & Hung, 2017;Hayden et al, 2019;Mead, Roe, et al, 2020;Viriyakosol, Kapoor, et al, 2019). Susceptibility to Coccidioides varies among mouse strains, with studies having shown that C57BL/6 and BALB/c mice are highly susceptible and that DBA/2 mice are more resistant (Kirkland & Fierer, 1983).…”

Section: Intranasal Infection Of Murine Modelsmentioning

confidence: 99%

Proper Care and Feeding of Coccidioides: A Laboratorian's Guide to Cultivating the Dimorphic Stages of C. immitis and C. posadasii

2020

View full text Add to dashboard Cite

Coccidioides immitis and C. posadasii. These fungi are thermally dimorphic, cycling between mycelia and arthroconidia in the environment and converting into spherules and endospores within a host. Coccidioides can cause a broad spectrum of disease that can be difficult to treat. There has been a steady increase in disease, with an estimated 350,000 new infections per year in the United States. With the increase in disease and difficulty in treatment, there is an unmet need to increase research in basic biology and identify new treatments, diagnostics, and vaccine candidates. Here, we describe protocols required in any Coccidioides laboratory, such as growing, harvesting, and storing the different stages of this dimorphic fungal pathogen.

show abstract

APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental Coccidioides immitis Pneumonia

Cited by 43 publications

References 33 publications

Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

Galactomannan Is a Biomarker of Fosmanogepix (APX001) Efficacy in Treating Experimental Invasive Pulmonary Aspergillosis

Aspiring Antifungals: Review of Current Antifungal Pipeline Developments

Proper Care and Feeding of Coccidioides: A Laboratorian's Guide to Cultivating the Dimorphic Stages of C. immitis and C. posadasii

Contact Info

Product

Resources

About