ArticleACS infectious diseases2018
GW779439X and Its Pyrazolopyridazine Derivatives Inhibit the Serine/Threonine Kinase Stk1 and Act As Antibiotic Adjuvants against β-Lactam-Resistant Staphylococcus aureus.
Article in ACS infectious diseases, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 34 citations in OpenAlex.
- Identification and characterization of inhibitors of the tuberculosis phosphatase PstP.The Journal of biological chemistry · 2026Article
- Emerging therapeutic drug targets in amino acid and protein biosynthesis pathways against ESKAPE and non-ESKAPE pathogens: a comprehensive review.Archives of microbiology · 2026Review
- Stk1 is required for BlaR1-mediated broad-spectrum β-lactam resistance in epidemic-causing strains ofResearch square · 2026Article
- Indolenine-substituted pyrazole derivative 4e inhibits planktonicAntimicrobial agents and chemotherapy · 2025Article
- The impacts of animal agriculture on One Health-Bacterial zoonosis, antimicrobial resistance, and beyond.One health (Amsterdam, Netherlands) · 2024Review
- Insights into Kinases of ESKAPE Pathogens for Therapeutic Interventions.Cardiovascular & hematological agents in medicinal chemistry · 2024Review
- Utilization of Existing Human Kinase Inhibitors as Scaffolds in the Development of New Antimicrobials.Antibiotics (Basel, Switzerland) · 2023Review
- Tyrosine Kinase Inhibitors Display Potent Activity against Cryptosporidium parvum.Microbiology spectrum · 2023Article
- Article
- Brominated Carbazole with Antibiotic Adjuvant Activity Displays Pleiotropic Effects in MRSA's Transcriptome.ACS chemical biology · 2022Article
- Identification and Evaluation of Brominated Carbazoles as a Novel Antibiotic Adjuvant Scaffold in MRSA.ACS medicinal chemistry letters · 2022Article
- Fatty Acids as Aminoglycoside Antibiotic Adjuvants AgainstFrontiers in microbiology · 2022Article
- Inhibitors targeting the autophosphorylation of serine/threonine kinase ofFrontiers in microbiology · 2022Article
- Evaluation of small molecule kinase inhibitors as novel antimicrobial and antibiofilm agents.Chemical biology & drug design · 2021Review
- PASTA kinase-dependent control of peptidoglycan synthesis via ReoM is required for cell wall stress responses, cytosolic survival, and virulence in Listeria monocytogenes.PLoS pathogens · 2021Article
- Discovery and Characterization of Selective and Ligand-Efficient DYRK Inhibitors.Journal of medicinal chemistry · 2021Article
- Review
- The enterococcal PASTA kinase: A sentinel for cell envelope stress.Molecular oral microbiology · 2021Review
- Engineering Selectivity for Reduced Toxicity of Bacterial Kinase Inhibitors Using Structure-Guided Medicinal Chemistry.ACS medicinal chemistry letters · 2021Article
- Crystal Structure and Inhibitor Identifications Reveal Targeting Opportunity for the Atypical MAPK Kinase ERK3.International journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
As antibiotic resistance rises, there is a need for strategies such as antibiotic adjuvants to conserve already-established antibiotics. A family of bacterial kinases known as the penicillin-binding-protein and serine/threonine kinase-associated (PASTA) kinases has attracted attention as targets for antibiotic adjuvants for β-lactams. Here, we report that the pyrazolopyridazine GW779439X sensitizes methicillin-resistant Staphylococcus aureus (MRSA) to various β-lactams through inhibition of the PASTA kinase Stk1. GW779439X potentiates β-lactam activity against multiple MRSA and MSSA isolates, including the sensitization of a ceftaroline-resistant isolate to ceftaroline. In silico modeling was used to guide the synthesis of GW779439X derivatives. The presence and orientation of GW779439X's methylpiperazine moiety was crucial for robust biochemical and microbiologic activity. Taken together, our data provide a proof of concept for developing the pyrazolopyridazines as selective Stk1 inhibitors which act across S. aureus isolates.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.