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September 5, 2025Journal of Chemical Information and ModelingOpen Access

Water-Based Pharmacophore Modeling in Kinase Inhibitor Design: A Case Study on Fyn and Lyn Protein Kinases

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Authors

MLMartin LjubičMDMarija Sollner DolencJBJure Borišek

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Overview

Observational analysis identifies active kinase inhibitors in Fyn and Lyn, suggesting water-based modeling aids virtual screening.

Key Points

  • Two active compounds were identified in biochemical assays, demonstrating the efficacy of water-based pharmacophore modeling in kinase inhibitor design.
  • Molecular dynamics simulations provided insights into interaction patterns, with key interactions retained in the bound states of identified hits.
  • Water-derived pharmacophores were generated to explore challenging targets in antitumor drug discovery, highlighting strengths and limitations in modeling.
  • Using water-based pharmacophores can enhance ligand-independent strategies for uncovering novel chemotypes in kinases and related therapeutic areas.

Cite This Study

Ljubič et al. (2025) studied this question.

synapsesocial.com/papers/68bb49cc6d6d5674bccffcb0https://doi.org/10.1021/acs.jcim.5c01478
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