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Experimental Therapeutics

A Second-Generation Fungerp Analog, SCY-247, Shows Potent In Vitro Activity against Candida auris and Other Clinically Relevant Fungal Isolates

Sherman Chu, Lisa Long, Rania Sherif, Thomas S. McCormick, Katyna Borroto-Esoda, Stephen Barat, Mahmoud A. Ghannoum
Sherman Chu
aDepartment of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA
bCollege of Osteopathic Medicine of the Pacific-Northwest (COMP), Lebanon, Oregon, USA
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Lisa Long
aDepartment of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA
dCenter for Medical Mycology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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Rania Sherif
aDepartment of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA
dCenter for Medical Mycology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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Thomas S. McCormick
aDepartment of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA
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Katyna Borroto-Esoda
cScynexis Inc., Jersey City, New Jersey, USA
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Stephen Barat
cScynexis Inc., Jersey City, New Jersey, USA
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Mahmoud A. Ghannoum
aDepartment of Dermatology, Case Western Reserve University, Cleveland, Ohio, USA
dCenter for Medical Mycology, University Hospitals Cleveland Medical Center, Cleveland, Ohio, USA
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  • ORCID record for Mahmoud A. Ghannoum
DOI: 10.1128/AAC.01988-20
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ABSTRACT

Due to the increase of antifungal drug resistance and difficulties associated with drug administration, new antifungal agents for invasive fungal infections are needed. SCY-247 is a second-generation fungerp antifungal compound that interferes with the synthesis of the fungal cell wall polymer β-(1,3)-d-glucan. We conducted an extensive antifungal screen of SCY-247 against yeast and mold strains compared with the parent compound ibrexafungerp (IBX; formerly SCY-078) to evaluate the in vitro antifungal properties of SCY-247. SCY-247 demonstrated similar activity to IBX against all of the organisms tested. Moreover, SCY-247 showed a higher percentage of fungicidal activity against the panel of yeast and mold isolates than IBX. Notably, SCY-247 showed considerable antifungal properties against numerous strains of Candida auris. Additionally, SCY-247 retained its antifungal activity when evaluated in the presence of synthetic urine, indicating that SCY-247 maintains activity and structural stability under environments with decreased pH levels. Finally, a time-kill study showed SCY-247 has potent anti-Candida, -Aspergillus, and -Scedosporium activity. In summary, SCY-247 has potent antifungal activity against various fungal species, indicating that further studies on this fungerp analog are warranted.

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A Second-Generation Fungerp Analog, SCY-247, Shows Potent In Vitro Activity against Candida auris and Other Clinically Relevant Fungal Isolates
Sherman Chu, Lisa Long, Rania Sherif, Thomas S. McCormick, Katyna Borroto-Esoda, Stephen Barat, Mahmoud A. Ghannoum
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01988-20; DOI: 10.1128/AAC.01988-20

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A Second-Generation Fungerp Analog, SCY-247, Shows Potent In Vitro Activity against Candida auris and Other Clinically Relevant Fungal Isolates
Sherman Chu, Lisa Long, Rania Sherif, Thomas S. McCormick, Katyna Borroto-Esoda, Stephen Barat, Mahmoud A. Ghannoum
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01988-20; DOI: 10.1128/AAC.01988-20
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KEYWORDS

ibrexafungerp
candidiasis
β-(1,3)-d-glucan
fungerps
triterpenoid class

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