Literature DB >> 30478166

SCY-078, a Novel Fungicidal Agent, Demonstrates Distribution to Tissues Associated with Fungal Infections during Mass Balance Studies with Intravenous and Oral [14C]SCY-078 in Albino and Pigmented Rats.

Stephen Wring1, Katyna Borroto-Esoda1, Eric Solon2, David Angulo3.   

Abstract

SCY-078, a fungicidal β-1,3-glucan synthesis inhibitor administered as intravenous or oral [14C]SCY-078 to rats, was distributed primarily into tissues associated with invasive fungal disease (kidney, lung, liver, spleen, bone marrow, muscle, vaginal tissue, and skin) to levels exceeding those in plasma. Oral fraction absorbed was ∼40%. Elimination was primarily via bile and feces (∼90%) and urine (∼1.5%). Mean half-time was ∼8 h. Quantitative whole-body autoradiography showed a rapid distribution at 8 h and elimination by 168 h postdose.
Copyright © 2019 American Society for Microbiology.

Entities:  

Keywords:  antifungal agents; mass balance

Mesh:

Substances:

Year:  2019        PMID: 30478166      PMCID: PMC6355592          DOI: 10.1128/AAC.02119-18

Source DB:  PubMed          Journal:  Antimicrob Agents Chemother        ISSN: 0066-4804            Impact factor:   5.191


  14 in total

1.  Enfumafungin derivative MK-3118 shows increased in vitro potency against clinical echinocandin-resistant Candida Species and Aspergillus species isolates.

Authors:  Cristina Jiménez-Ortigosa; Padmaja Paderu; Mary R Motyl; David S Perlin
Journal:  Antimicrob Agents Chemother       Date:  2013-12-09       Impact factor: 5.191

2.  Pharmacokinetics and tissue distribution of anidulafungin in rats.

Authors:  Bharat Damle; Martin Stogniew; James Dowell
Journal:  Antimicrob Agents Chemother       Date:  2008-04-28       Impact factor: 5.191

3.  Compartmental pharmacokinetics and tissue distribution of the antifungal echinocandin lipopeptide micafungin (FK463) in rabbits.

Authors:  A H Groll; D Mickiene; V Petraitis; R Petraitiene; K H Ibrahim; S C Piscitelli; I Bekersky; T J Walsh
Journal:  Antimicrob Agents Chemother       Date:  2001-12       Impact factor: 5.191

4.  In vitro activity of a new oral glucan synthase inhibitor (MK-3118) tested against Aspergillus spp. by CLSI and EUCAST broth microdilution methods.

Authors:  Michael A Pfaller; Shawn A Messer; Mary R Motyl; Ronald N Jones; Mariana Castanheira
Journal:  Antimicrob Agents Chemother       Date:  2012-12-10       Impact factor: 5.191

Review 5.  Echinocandins: The Expanding Antifungal Armamentarium.

Authors:  Daniel Aguilar-Zapata; Ruta Petraitiene; Vidmantas Petraitis
Journal:  Clin Infect Dis       Date:  2015-12-01       Impact factor: 9.079

6.  Activity of MK-3118, a new oral glucan synthase inhibitor, tested against Candida spp. by two international methods (CLSI and EUCAST).

Authors:  Michael A Pfaller; Shawn A Messer; Mary R Motyl; Ronald N Jones; Mariana Castanheira
Journal:  J Antimicrob Chemother       Date:  2012-11-28       Impact factor: 5.790

7.  Disposition of caspofungin: role of distribution in determining pharmacokinetics in plasma.

Authors:  Julie A Stone; Xin Xu; Gregory A Winchell; Paul J Deutsch; Paul G Pearson; Elizabeth M Migoya; Goutam C Mistry; Liwen Xi; Alisha Miller; Punam Sandhu; Romi Singh; Florencia deLuna; Stacy C Dilzer; Kenneth C Lasseter
Journal:  Antimicrob Agents Chemother       Date:  2004-03       Impact factor: 5.191

Review 8.  Tissue penetration of antifungal agents.

Authors:  Timothy Felton; Peter F Troke; William W Hope
Journal:  Clin Microbiol Rev       Date:  2014-01       Impact factor: 26.132

Review 9.  Pharmacology and metabolism of anidulafungin, caspofungin and micafungin in the treatment of invasive candidosis: review of the literature.

Authors:  G Kofla; Markus Ruhnke
Journal:  Eur J Med Res       Date:  2011-04-28       Impact factor: 2.175

10.  Preclinical Pharmacokinetics and Pharmacodynamic Target of SCY-078, a First-in-Class Orally Active Antifungal Glucan Synthesis Inhibitor, in Murine Models of Disseminated Candidiasis.

Authors:  Stephen A Wring; Ryan Randolph; SeongHee Park; George Abruzzo; Qing Chen; Amy Flattery; Graig Garrett; Michael Peel; Russell Outcalt; Kendall Powell; Michelle Trucksis; David Angulo; Katyna Borroto-Esoda
Journal:  Antimicrob Agents Chemother       Date:  2017-03-24       Impact factor: 5.191

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  14 in total

1.  Efficacy of Ibrexafungerp (SCY-078) against Candida auris in an In Vivo Guinea Pig Cutaneous Infection Model.

Authors:  M Ghannoum; N Isham; D Angulo; K Borroto-Esoda; S Barat; L Long
Journal:  Antimicrob Agents Chemother       Date:  2020-09-21       Impact factor: 5.191

2.  Penetration of Ibrexafungerp (Formerly SCY-078) at the Site of Infection in an Intra-abdominal Candidiasis Mouse Model.

Authors:  Annie Lee; Brendan Prideaux; Matthew Zimmerman; Claire Carter; Stephen Barat; David Angulo; Véronique Dartois; David S Perlin; Yanan Zhao
Journal:  Antimicrob Agents Chemother       Date:  2020-02-21       Impact factor: 5.191

3.  Invasive candidiasis: investigational drugs in the clinical development pipeline and mechanisms of action.

Authors:  Martin Hoenigl; Rosanne Sprute; Amir Arastehfar; John R Perfect; Cornelia Lass-Flörl; Romuald Bellmann; Juergen Prattes; George R Thompson; Nathan P Wiederhold; Mohanad M Al Obaidi; Birgit Willinger; Maiken C Arendrup; Philipp Koehler; Matteo Oliverio; Matthias Egger; Ilan S Schwartz; Oliver A Cornely; Peter G Pappas; Robert Krause
Journal:  Expert Opin Investig Drugs       Date:  2022-06-15       Impact factor: 6.498

4.  Ibrexafungerp Versus Placebo for Vulvovaginal Candidiasis Treatment: A Phase 3, Randomized, Controlled Superiority Trial (VANISH 303).

Authors:  Jane R Schwebke; Ryan Sobel; Janet K Gersten; Steven A Sussman; Samuel N Lederman; Mark A Jacobs; B Todd Chappell; David L Weinstein; Alfred H Moffett; Nkechi E Azie; David A Angulo; Itzel A Harriott; Katyna Borroto-Esoda; Mahmoud A Ghannoum; Paul Nyirjesy; Jack D Sobel
Journal:  Clin Infect Dis       Date:  2022-06-10       Impact factor: 20.999

5.  Impact of FKS1 Genotype on Echinocandin In Vitro Susceptibility in Candida auris and In Vivo Response in a Murine Model of Infection.

Authors:  Dipti Sharma; Raees A Paul; Shivaprakash M Rudramurthy; Nisha Kashyap; Sanjay Bhattacharya; Rajeev Soman; Shamanth A Shankarnarayan; Dipali Chavan; Shreya Singh; Parijit Das; Harsimran Kaur; Anup K Ghosh; Rajendra Prasad; Kaustuv Sanyal; Arunaloke Chakrabarti
Journal:  Antimicrob Agents Chemother       Date:  2021-11-15       Impact factor: 5.938

Review 6.  Ibrexafungerp: A Novel Oral Triterpenoid Antifungal in Development for the Treatment of Candida auris Infections.

Authors:  Mahmoud Ghannoum; Maiken Cavling Arendrup; Vishnu P Chaturvedi; Shawn R Lockhart; Thomas S McCormick; Sudha Chaturvedi; Elizabeth L Berkow; Deven Juneja; Bansidhar Tarai; Nkechi Azie; David Angulo; Thomas J Walsh
Journal:  Antibiotics (Basel)       Date:  2020-08-25

7.  Efficacy and safety of oral ibrexafungerp for the treatment of acute vulvovaginal candidiasis: a global phase 3, randomised, placebo-controlled superiority study (VANISH 306).

Authors:  R Sobel; P Nyirjesy; M A Ghannoum; D A Delchev; N E Azie; D Angulo; I A Harriott; K Borroto-Esoda; J D Sobel
Journal:  BJOG       Date:  2021-11-08       Impact factor: 7.331

Review 8.  Ibrexafungerp: A First-in-Class Oral Triterpenoid Glucan Synthase Inhibitor.

Authors:  Sabelle Jallow; Nelesh P Govender
Journal:  J Fungi (Basel)       Date:  2021-02-25

9.  In Vitro pH Activity of Ibrexafungerp against Fluconazole-Susceptible and -Resistant Candida Isolates from Women with Vulvovaginal Candidiasis.

Authors:  Jack D Sobel; Katyna Borroto-Esoda; Nkechi Azie; David Angulo
Journal:  Antimicrob Agents Chemother       Date:  2021-07-16       Impact factor: 5.191

Review 10.  Ibrexafungerp, a Novel Oral Triterpenoid Antifungal in Development: Overview of Antifungal Activity Against Candida glabrata.

Authors:  Ahmed Gamal; Sherman Chu; Thomas S McCormick; Katyna Borroto-Esoda; David Angulo; Mahmoud A Ghannoum
Journal:  Front Cell Infect Microbiol       Date:  2021-03-11       Impact factor: 5.293

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