<i>In Vitro</i>
            Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms

Arendrup, Maiken Cavling; Hare, Rasmus Krøger; Cuenca‐Estrella, Manuel

doi:10.1128/aac.02336-15

Cited by 32 publications

(17 citation statements)

References 17 publications

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“…), ASP2397 (Vical; compound with a novel and as‐yet‐unknown target different from that of licensed antifungal agents, with activity against Aspergillus and C. glabrata ; Arendrup et al . ), celecoxib derivative AR 12 (Arno Therapeutics; has a broad spectrum of activity, including activity against yeasts, molds and dimorphic fungi; Koselny et al . ), orotomide class (F901318 [F2G]; has potent in vitro activity against Scedosporium species and Lomentospora prolificans ; Wiederhold et al .…”

Section: Strategies To Combat Fungal Resistancementioning

confidence: 99%

Antifungals discovery: an insight into new strategies to combat antifungal resistance

Fuentefría

Pippi

Lana

et al. 2018

Letters in Applied Microbiology

144

109

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Significance and Impact of the Study: The failure to respond to antifungal therapy is complex and is associated with microbiological resistance and increased expression of virulence in fungal pathogens. Thus, this review offers an overview of current challenges in the treatment of fungal infections associated with increased antifungal drug resistance and the formation of biofilms in these opportunistic pathogens. Furthermore, the most recent and potential strategies to combat fungal pathogens are explored here, focusing on new agents as well as innovative approaches, such as combination therapy between antifungal drugs or with natural compounds. AbstractUndeniably, new antifungal treatments are necessary against pathogenic fungi. Fungal infections have significantly increased in recent decades, being highlighted as important causes of morbidity and mortality, particularly in immunocompromised patients. Five main antifungal classes are used: (i) azoles, (ii) echinocandins, (iii) polyenes, (iv) allylamines and (v) pyrimidine analogues. Moreover, the treatment of mycoses has several limitations, such as undesirable side effects, narrow activity spectrum, a small number of targets and fungal resistance, which are still of major concern in clinical practice. The discovery of new antifungals is mostly achieved by the screening of natural or synthetic/semisynthetic chemical compounds. The most recent discoveries in drug resistance mechanism and their avoidance were explored in a review, focusing on different antifungal targets, as well as new agents or strategies, such as combination therapy, that could improve antifungal therapy.

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Section: Strategies To Combat Fungal Resistancementioning

confidence: 99%

Antifungals discovery: an insight into new strategies to combat antifungal resistance

Fuentefría

Pippi

Lana

et al. 2018

Letters in Applied Microbiology

144

109

View full text Add to dashboard Cite

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“…The results were consistent with previous reports: MIC 100 values of ϳ1 M (ϳ1 g/ml) for both drugs against azole-sensitive strains and MIC 100 values of Ͼ45 M (Ͼ32 g/ml) for the azole-resistant strain F11628. Strain F16216 was sensitive to posaconazole (MIC 100 of 2.5 M or 1.7 g/ml) and resistant to itraconazole (MIC 100 of 45 M or 32 g/ml) ( Table 7) (25).…”

Section: Figmentioning

confidence: 99%

A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens

Rank

Walsh

Liu

et al. 2017

Antimicrob Agents Chemother

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Invasive fungal diseases are generally difficult to treat and often fatal. The therapeutic agents available to treat fungi are limited, and there is a critical need for new agents to combat these deadly infections. Antifungal compound development has been hindered by the challenge of creating agents that are highly active against fungal pathogens but not toxic to the host. Host defense peptides (HDPs) are produced by eukaryotes as a component of the innate immune response to pathogens and have served as inspiration for the development of many new antibacterial compounds. HDP mimics, however, have largely failed to exhibit potent and selective antifungal activity. Here, we present an HDP-like nylon-3 copolymer that is effective against diverse fungi while displaying only mild to moderate toxicity toward mammalian cells. This polymer is active on its own and in synergy with existing antifungal drugs against multiple species of and, reaching levels of efficacy comparable to those of the clinical agents amphotericin B and fluconazole in some cases. In addition, the polymer acts synergistically with azoles against different species of , including some azole-resistant strains. These findings indicate that nylon-3 polymers are a promising lead for development of new antifungal therapeutic strategies.

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“…VL-2397 has demonstrated in vitro activity against Aspergillus species, including azole-resistant strains, and Fusarium species. 106,108 A phase 3 study was launched in invasive aspergillosis, but clinical development was terminated by business decision after enrollment of four patients (https://clinicaltrials.gov). • Manogepix (APX001A and formerly E1210) is an oral and IV broad-spectrum antifungal targeting the highly conserved fungal enzyme Gwt1.…”

Section: Discussionmentioning

confidence: 99%

Antifungal Therapy: New and Evolving Therapies

Nivoix

Ledoux

Herbrecht

2020

Semin Respir Crit Care Med

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Invasive fungal diseases primarily occur in immunocompromised patients. Immunosuppression has become more prevalent due to novel treatments, and this has led to a rise in the incidence of invasive fungal diseases. The antifungal armamentarium has long been insufficient and has taken quite some time to become diverse. Antifungal spectrum, tolerability, and toxicity are critical issues. Amphotericin B and its lipid formulations still have the widest spectrum, but, in spite of the better tolerance of the lipid formulations, toxicity remains a drawback, mostly with regard to renal function. Azoles constitute a heterogeneous antifungal class, in which newer molecules have an improved spectrum of activity. The main concern for the clinician when using azoles relates to the management of their many potential drug–drug interactions in an often fragile patient population. Echinocandins are better tolerated but possess a narrower antifungal spectrum and lack an oral route of administration. Still, their fungicidal activity makes them a weapon of first choice against Candida species. For certain uncommon fungal infections, antifungals such as flucytosine and terbinafine can also be useful. This article will give an overview of the mechanisms of action of currently used antifungals, as well as their spectrum of activity, clinically relevant pharmacological features, drug–drug interactions, and frequent side effects, all of which should drive the clinician's choice of agent when managing invasive fungal infections.

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In Vitro Activity of ASP2397 against Aspergillus Isolates with or without Acquired Azole Resistance Mechanisms

Cited by 32 publications

References 17 publications

Antifungals discovery: an insight into new strategies to combat antifungal resistance

Antifungals discovery: an insight into new strategies to combat antifungal resistance

A Cationic Polymer That Shows High Antifungal Activity against Diverse Human Pathogens

Antifungal Therapy: New and Evolving Therapies

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