Literature DB >> 34310205

In Vitro Activity of APX2041, a New Gwt1 Inhibitor, and In Vivo Efficacy of the Prodrug APX2104 against Aspergillus fumigatus.

Shareef K Shaheen1, Praveen R Juvvadi1, John Allen1, E Keats Shwab1, D Christopher Cole1, Yohannes G Asfaw2, Mili Kapoor3, Karen Joy Shaw4, William J Steinbach1,5.   

Abstract

Invasive aspergillosis (IA) due to Aspergillus fumigatus is a deadly infection for which new antifungal therapies are needed. Here, we demonstrate the efficacy of a Gwt1 inhibitor, APX2041, and its prodrug, APX2104, against A. fumigatus. The wild-type, azole-resistant, and echinocandin-resistant A. fumigatus strains were equally susceptible to APX2041 in vitro. APX2104 treatment in vivo significantly prolonged survival of neutropenic mice challenged with the wild-type and azole-resistant strains, revealing APX2104 as a potentially promising therapeutic against IA.

Entities:  

Keywords:  APX001; APX001A; APX2041; APX2104; Aspergillus fumigatus; Gwt1; fosmanogepix; invasive aspergillosis; manogepix; murine model

Mesh：

Substances：

Year:  2021        PMID： 34310205      PMCID： PMC8448089          DOI： 10.1128/AAC.00682-21

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


  21 in total

1.  Genomic perspective of triazole resistance in clinical and environmental Aspergillus fumigatus isolates without cyp51A mutations.

Authors:  Cheshta Sharma; Shijulal Nelson-Sathi; Ashutosh Singh; M Radhakrishna Pillai; Anuradha Chowdhary
Journal:  Fungal Genet Biol       Date:  2019-08-26       Impact factor: 3.495

2.  Risk stratification for invasive aspergillosis in immunocompromised patients.

Authors:  Raoul Herbrecht; Pierre Bories; Jean-Charles Moulin; Marie-Pierre Ledoux; Valérie Letscher-Bru
Journal:  Ann N Y Acad Sci       Date:  2012-12       Impact factor: 5.691

Review 3.  Triazole resistance in Aspergillus fumigatus: recent insights and challenges for patient management.

Authors:  P P A Lestrade; J F Meis; W J G Melchers; P E Verweij
Journal:  Clin Microbiol Infect       Date:  2018-12-21       Impact factor: 8.067

4.  Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America.

Authors:  Thomas F Patterson; George R Thompson; David W Denning; Jay A Fishman; Susan Hadley; Raoul Herbrecht; Dimitrios P Kontoyiannis; Kieren A Marr; Vicki A Morrison; M Hong Nguyen; Brahm H Segal; William J Steinbach; David A Stevens; Thomas J Walsh; John R Wingard; Jo-Anne H Young; John E Bennett
Journal:  Clin Infect Dis       Date:  2016-06-29       Impact factor: 9.079

5.  In Vitro Activity of Manogepix (APX001A) and Comparators against Contemporary Molds: MEC Comparison and Preliminary Experience with Colorimetric MIC Determination.

Authors:  Karin Meinike Jørgensen; Karen M T Astvad; Maiken Cavling Arendrup
Journal:  Antimicrob Agents Chemother       Date:  2020-07-22       Impact factor: 5.191

6.  Plasma membrane localization is required for RasA-mediated polarized morphogenesis and virulence of Aspergillus fumigatus.

Authors:  Jarrod R Fortwendel; Praveen R Juvvadi; Luise E Rogg; Yohannes G Asfaw; Kimberlie A Burns; Scott H Randell; William J Steinbach
Journal:  Eukaryot Cell       Date:  2012-05-04

7.  Fosmanogepix (APX001) Is Effective in the Treatment of Immunocompromised Mice Infected with Invasive Pulmonary Scedosporiosis or Disseminated Fusariosis.

Authors:  Sondus Alkhazraji; Teclegiorgis Gebremariam; Abdullah Alqarihi; Yiyou Gu; Zeinab Mamouei; Shakti Singh; Nathan P Wiederhold; Karen J Shaw; Ashraf S Ibrahim
Journal:  Antimicrob Agents Chemother       Date:  2020-02-21       Impact factor: 5.191

8.  In Vitro and In Vivo Evaluation of APX001A/APX001 and Other Gwt1 Inhibitors against Cryptococcus.

Authors:  Karen Joy Shaw; Wiley A Schell; Jonathan Covel; Gisele Duboc; C Giamberardino; Mili Kapoor; Molly Moloney; Quinlyn A Soltow; Jennifer L Tenor; Dena L Toffaletti; Michael Trzoss; Peter Webb; John R Perfect
Journal:  Antimicrob Agents Chemother       Date:  2018-07-27       Impact factor: 5.191

9.  APX001 and Other Gwt1 Inhibitor Prodrugs Are Effective in Experimental Coccidioides immitis Pneumonia.

Authors:  Suganya Viriyakosol; Mili Kapoor; Sharon Okamoto; Jonathan Covel; Quinlyn A Soltow; Michael Trzoss; Karen Joy Shaw; Joshua Fierer
Journal:  Antimicrob Agents Chemother       Date:  2019-01-29       Impact factor: 5.191

10.  APX001 Is Effective in the Treatment of Murine Invasive Pulmonary Aspergillosis.

Authors:  Teclegiorgis Gebremariam; Sondus Alkhazraji; Abdullah Alqarihi; Heewon H Jeon; Yiyou Gu; Mili Kapoor; Karen J Shaw; Ashraf S Ibrahim
Journal:  Antimicrob Agents Chemother       Date:  2019-01-29       Impact factor: 5.191
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