Evaluation of the Antifungal Activity of the Novel Oral Glucan Synthase Inhibitor SCY-078, Singly and in Combination, for the Treatment of Invasive Aspergillosis

Ghannoum, Mahmoud A.; Long, Lisa; Larkin, Emily L; Isham, N.; Sherif, R.; Borroto–Esoda, Katyna; Barat, Stephen; Angulo, David

doi:10.1128/aac.00244-18

Cited by 67 publications

(54 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, due to the limited antifungal activity of these drugs against Aspergillus spp., echinocandins compounds are used only as an alternative or a salvage therapy for the treatment of invasive aspergillosis when the first line therapy with azole drugs fails (Aruanno et al, 2019). It is noteworthy that a new antifungal drug called ibrexafungerp (SCY-078) has a broad in vitro and in vivo activity against a broad spectrum of Aspergillus species (Ghannoum et al, 2018).…”

Section: Cell Wall As An Antifungal Targetmentioning

confidence: 99%

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species

et al. 2020

View full text Add to dashboard Cite

The fungal cell wall is located outside the plasma membrane and is the cell compartment that mediates all the relationships of the cell with the environment. It protects the contents of the cell, gives rigidity and defines the cellular structure. The cell wall is a skeleton with high plasticity that protects the cell from different stresses, among which osmotic changes stand out. The cell wall allows interaction with the external environment since some of its proteins are adhesins and receptors. Since, some components have a high immunogenic capacity, certain wall components can drive the host's immune response to promote fungus growth and dissemination. The cell wall is a characteristic structure of fungi and is composed mainly of glucans, chitin and glycoproteins. As the components of the fungal cell wall are not present in humans, this structure is an excellent target for antifungal therapy. In this article, we review recent data on the composition and synthesis, influence of the components of the cell wall in fungi-host interaction and the role as a target for the next generation of antifungal drugs in yeasts (Candida and Cryptococcus) and filamentous fungi (Aspergillus).

show abstract

Section: Cell Wall As An Antifungal Targetmentioning

confidence: 99%

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species

et al. 2020

View full text Add to dashboard Cite

show abstract

“…and A. fumigatus isolates (91,92). Ibrexafungerp demonstrated synergistic in vitro activity in combination with mold-active azoles (voriconazole, isavuconazole) or amphotericin B against azole-susceptible A. fumigatus (90), and a phase 2 clinical trial that will test the efficacy of the ibrexafungerp-voriconazole combination versus voriconazole monotherapy for the treatment of IA is forthcoming.…”

Section: Echinocandins In Clinical Practicementioning

confidence: 99%

“…Ibrexafungerp has the advantage of bioavailability by the oral route and an antifungal spectrum similar to that of echinocandins with fungistatic activity against Aspergillus spp. In vitro testing showed MECs ranging from 0.06 to 0.25 g/ml for the most relevant pathogenic Aspergillus spp., including azole-resistant A. fumigatus (89,90). Because ibrexafungerp targets a different region of the ␤-glucan synthase than echinocandins, its activity is not affected by the common hot spot mutations described in Candida spp.…”

Section: Echinocandins In Clinical Practicementioning

confidence: 99%

Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside

Aruanno

Glampedakis

Lamoth

2019

Antimicrob Agents Chemother

View full text Add to dashboard Cite

Echinocandins (caspofungin, micafungin, anidulafungin), targeting ␤-1,3glucan synthesis of the cell wall, represent one of the three currently available antifungal drug classes for the treatment of invasive fungal infections. Despite their limited antifungal activity against Aspergillus spp., echinocandins are considered an alternative option for the treatment of invasive aspergillosis (IA). This drug class exhibits several advantages, such as excellent tolerability and its potential for synergistic interactions with some other antifungals. The objective of this review is to discuss the in vitro and clinical efficacy of echinocandins against Aspergillus spp., considering the complex interactions between the drug, the mold, and the host. The antifungal effect of echinocandins is not limited to direct inhibition of hyphal growth but also induces an immunomodulatory effect on the host's response. Moreover, Aspergillus spp. have developed important adaptive mechanisms of tolerance to survive and overcome the action of echinocandins, such as paradoxical growth at increased concentrations. This stress response can be abolished by several compounds that potentiate the activity of echinocandins, such as drugs targeting the heat shock protein 90 (Hsp90)-calcineurin axis, opening perspectives for adjuvant therapies. Finally, the present and future places of echinocandins as prophylaxis, monotherapy, or combination therapy of IA are discussed in view of the emergence of pan-azole resistance among Aspergillus fumigatus isolates, the occurrence of breakthrough IA, and the advent of new long-lasting echinocandins (rezafungin) or other ␤-1,3-glucan synthase inhibitors (ibrexafungerp). KEYWORDS Aspergillus, anidulafungin, calcineurin, caspofungin, heat shock protein 90, ibrexafungerp, micafungin, paradoxical effect, rezafungin M olds of the genus Aspergillus (particularly, Aspergillus fumigatus) are the causal agents of invasive aspergillosis (IA), a life-threatening infection affecting immunocompromised hosts, such as hematological cancer or transplant patients. The current antifungal armamentarium for the treatment of IA is limited to three antifungal drug classes. Fungicidal drugs, such as the triazoles (e.g., voriconazole, posaconazole, or isavuconazole) and the polyenes (amphotericin B formulations) represent the firstchoice treatments, whereas the fungistatic echinocandins (caspofungin, anidulafungin, and micafungin) represent an alternative and are only marginally used as monotherapy (1, 2). However, use of echinocandins is gaining interest because of the emergence of acquired azole resistance in A. fumigatus isolates and the limitations related to drug interactions and/or toxicity with azoles and amphotericin B. The aim of this review is to discuss the role of the echinocandins in the treatment of IA, from the mechanistic point of view of drug-pathogen-host interactions to clinical application and perspectives. ECHINOCANDINS AGAINST ASPERGILLUSMechanisms of action. The echinocandin drugs are lipopeptides derived from fu...

show abstract

“…Ibrexafungerp (formerly SCY-078) is a new antifungal triterpenoid glucan synthase inhibitor that has shown in vitro activity against Candida and Aspergillus [32][33][34]. It is currently in six clinical trials testing the efficacy of ibrexafungerp against candidiasis caused by Candida auris (CARES), vulvovaginal candidiasis (VVC), and invasive pulmonary aspergillosis.…”

Section: Antifungals In the Pipelinementioning

confidence: 99%

Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery

Marquez

Quave

2020

Antibiotics

View full text Add to dashboard Cite

Antimicrobial resistance is a global issue that threatens the effective practice of modern medicine and global health. The emergence of multidrug-resistant (MDR) fungal strains of Candida auris and azole-resistant Aspergillus fumigatus were highlighted in the Centers for Disease Control and Prevention’s (CDC) 2019 report, Antibiotic Resistance Threats in the United States. Conventional antifungals used to treat fungal infections are no longer as effective, leading to increased mortality. Compounding this issue, there are very few new antifungals currently in development. Plants from traditional medicine represent one possible research path to addressing the issue of MDR fungal pathogens. In this commentary piece, we discuss how medical ethnobotany—the study of how people use plants in medicine—can be used as a guide to identify plant species for the discovery and development of novel antifungal therapies.

show abstract

Evaluation of the Antifungal Activity of the Novel Oral Glucan Synthase Inhibitor SCY-078, Singly and in Combination, for the Treatment of Invasive Aspergillosis

Cited by 67 publications

References 17 publications

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species

The Fungal Cell Wall: Candida, Cryptococcus, and Aspergillus Species

Echinocandins for the Treatment of Invasive Aspergillosis: from Laboratory to Bedside

Prevalence and Therapeutic Challenges of Fungal Drug Resistance: Role for Plants in Drug Discovery

Contact Info

Product

Resources

About