Raf-kinase inhibitor GW5074 shows antibacterial activity against methicillin-resistant Staphylococcus aureus and potentiates the activity of gentamicin

Tatiana Johnston, Gabriel Lambert Hendricks, Steven Shen, Roy Fangxing Chen, Bumsup Kwon, Michael John Kelso, Wooseong Kim, Beth Burgwyn Fuchs, Eleftherios Mylonakis

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Aim: Increasing antimicrobial resistance has compromised the effectiveness of many antibiotics, including those used to treat staphylococcal infections like methicillin-resistant Staphylococcus aureus. The development of combination therapies, where antimicrobial agents are used with compounds that inhibit resistance pathways is a promising strategy. Results/methodology: The Raf kinase inhibitor GW5074 exhibited selective in vitro activity against Gram-positive bacteria, including clinical isolates of S. aureus with a minimum inhibitory concentration (MIC) of 2-8 μg/ml. GW5074 was effective in vivo in the Galleria mellonella infection model. The compound showed synergy with gentamicin by lowering MIC by fourfold, compared with gentamicin MIC alone. Conclusion: This work demonstrates the antimicrobial properties of GW5074 and supports further investigation of the kinase inhibitors as antibiotic adjuvants.

Original languageEnglish
Pages (from-to)1941-1952
Number of pages12
JournalFuture Medicinal Chemistry
Volume8
Issue number16
DOIs
StatePublished - Oct 2016

Keywords

  • GW5074
  • Staphylococcus aureus
  • gentamicin

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