Ibrexafungerp: An orally active β-1,3-glucan synthesis inhibitor

Apgar, James M.; Wilkening, Robert R.; Parker, Dann L.; Meng, Dongfang; Wildonger, Kenneth J.; Sperbeck, Donald M.; Greenlee, Mark L.; Balkovec, James M.; Flattery, Amy; Abruzzo, George K.; Galgoci, Andrew; Giacobbe, Robert A.; Gill, Charles; Hsu, Ming-Jo; Liberator, Paul; Misura, Andrew S.; Motyl, Mary; Kahn, Jennifer Nielsen; Powles, M A; Racine, Fred; Dragovic, Jasminka; Wu, Fan; Kirwan, Robin; Lee, Shu; Líu, Hao; Mamai, Ahmed; Nelson, Kingsley H.; Peel, Michael R.

doi:10.1016/j.bmcl.2020.127661

Cited by 29 publications

(16 citation statements)

References 28 publications

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“…In VANISH 303, clinical cure, mycological eradication, and clinical improvement at day 25 were 51 vs 29%, 50 vs 19%, and 64 vs 37% in the ibrexafungerp group compared with placebo [ 11 , 25 ]. In VANISH 306, 188 patients with acute vulvovaginal candidiasis were randomized to receive ibrexafungerp or placebo in a 2:1 ratio [ 9 ]. The primary endpoint of the trial was clinical cure rate, defined as the complete resolution of all signs and symptoms at the test-of-cure visit on day 10.…”

Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

“…Ibrexafungerp is a first-in-class triterpenoid antifungal agent that is available in an oral formulation. Similar to echinocandins, ibrexafungerp inhibits (1→3)-β- d -glucan synthase, a key component of the fungal cell wall, and has both in vitro and in vivo activity against a variety of clinically relevant fungal species, including the yeast Candida and the mold Aspergillus [ 9 , 10 ] . However, the full spectrum of activity of ibrexafungerp is not yet known, especially against invasive mold infections such as mucormycosis, scedosporiosis, and fusariosis.…”

Section: Introductionmentioning

confidence: 99%

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Pharmacokinetics and Pharmacodynamics of Ibrexafungerp

McCarthy

2021

Drugs R D

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On 2 June, 2021, the US Food and Drug Administration approved ibrexafungerp (formerly MK-3118 and SCY-078) for the treatment of vulvovaginal candidiasis, also known as vaginal yeast infection. Ibrexafungerp is the first drug approved in a novel antifungal class in more than two decades, and the Food and Drug Administration's decision was based on positive results from two pivotal phase III studies in which oral ibrexafungerp proved both safe and effective in patients with vulvovaginal candidiasis. The decision was also based on substantial preclinical and clinical work in both the pharmacokinetics and pharmacodynamics of ibrexafungerp. This paper reviews that research and looks ahead to explore how this novel antifungal agent may be used in the future to address the expanding problem of drug-resistant mycotic infections.

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Section: Pharmacokinetics and Pharmacodynamicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Ibrexafungerp

McCarthy

2021

Drugs R D

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“…This is the first of the triterpinoid antifungals ( Davis et al., 2020 ). It is structurally similar to the echinocandins, and its mechanism of action is similarly through inhibition of β-1,3-glucan synthase, but its binding site is slightly different than that of the echinocandins, but with some overlap in the binding region ( Apgar et al., 2021 ). Through this small molecular change, ibrexafungerp maintains activity against both echinocandin susceptible and certain resistant pathogens, especially selected echinocandin resistant Candida spp.…”

Section: Ibrexafungerp (Scynexis Formerly Scy-078)mentioning

confidence: 99%

Antifungal Pipeline

McCarty

Pappas

2021

Front. Cell. Infect. Microbiol.

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In many ways, fungal diseases are forgotten or neglected. Given the significantly lower frequency compared to similar bacterial etiologies across the spectrum of infectious syndromes, it makes sense that anti-bacterial agents have seen the bulk of development in recent decades. The vast majority of new antifungal medications approved for use in the past 10 years have been new versions in the same class as existing agents. Clinical mycology is crying out for new mechanisms of action in the setting of rising resistance and emergence of new organisms. Fortunately, this trend appears to be reversing. There are numerous agents in advanced stages of development offering novel dosing regimens and mechanisms of action to combat these threats. Herein we review seven antifungal agents that we hope to see come to market in the coming years to aid physicians in the treatment of mucocutaneous and invasive fungal infections.

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“…In 1962, Corey and Chaykovsky introduced dimethylsulfoxonium methylide (DMSOM) into synthetic practice as a reagent for the simple and efficient construction of three-membered rings, i.e., oxiranes, aziridines, and cyclopropanes from the corresponding carbonyl compounds, their imines and acceptor alkenes, respectively (Scheme 1). [1][2][3][4][5] Immediately after the first paper describing this reagent, now called the Corey ylide, multiple studies began to appear on the use of DMSOM in various reactions with diverse unsaturated compounds. 2 Among these transformations, two types of reactions attract particular attention.…”

Section: Introductionmentioning

confidence: 99%