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A Second-Generation Fungerp Analog, SCY-247, Shows Potent

Authors :
Sherman, Chu
Lisa, Long
Thomas S, McCormick
Katyna, Borroto-Esoda
Stephen, Barat
Mahmoud A, Ghannoum
Source :
Antimicrob Agents Chemother
Publication Year :
2020

Abstract

Echinocandins are a first-line therapy for Candida infections through their ability to inhibit the synthesis of polymer β-(1,3)-d-glucan. However, there has been an emergence of multidrug-resistant fungal species necessitating the development of novel antifungal agents to combat invasive fungal infections. SCY-247, a second-generation glucan synthase inhibitor of the triterpenoid class (fungerps), is currently being developed as a potential therapy option. We determined the pharmacokinetics (PKs) of SCY-247 following oral (gavage) administration in mice and evaluated the efficacy of SCY-247 in a murine model of hematogenously disseminated candidiasis caused by Candida albicans. Plasma concentrations of SCY-247 were measurable through the last collected time point in all dose groups. Mean concentrations of SCY-247 increased with dose levels, with concentrations of SCY-247 higher after multiple doses than after a single dose. Treatment with SCY-247 resulted in decreased fungal burden and improvement in survival rates against C. albicans disseminated infection. Treatment with 10 mg/kg of body weight of SCY-247 showed a significant reduction in CFU compared with the untreated control (3-log decrease on average) (P = 0.008). Similarly, 40 mg/kg SCY-247 demonstrated a statistically significant reduction in kidney CFU compared with untreated mice (average log CFU ± SD of 2.38 ± 2.58 versus 6.26 ± 0.51; P = 0.001). Mice treated with SCY-247 at 40 mg/kg exhibited a 100% survival rate at the end of the study, contrasted with 62.5% (5 of 8) survival rate in untreated mice. The results of this investigation indicate that SCY-247 is a promising novel anti-fungal agent with activity against Candida infections.

Details

ISSN :
10986596
Volume :
65
Issue :
3
Database :
OpenAIRE
Journal :
Antimicrobial agents and chemotherapy
Accession number :
edsair.pmid..........9122d1dcc3eff9ef9241894be73c707e