ArticleACS medicinal chemistry letters2021
Discovery of Aminopyrazole Derivatives as Potent Inhibitors of Wild-Type and Gatekeeper Mutant FGFR2 and 3.
Article in ACS medicinal chemistry letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
6 citing papers in PubMed.
- Developing New Peptides and Peptide-Drug Conjugates for Targeting the FGFR2 Receptor-Expressing Tumor Cells and 3D Spheroids.Biomimetics (Basel, Switzerland) · 2024Article
- Targeting FGFR for cancer therapy.Journal of hematology & oncology · 2024Review
- The Irreversible FGFR Inhibitor KIN-3248 Overcomes FGFR2 Kinase Domain Mutations.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Allosteric inhibition of tRNA synthetase Gln4 by N-pyrimidinyl-β-thiophenylacrylamides exerts highly selective antifungal activity.Cell chemical biology · 2024Article
- The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.Nature communications · 2024Article
- Discovery of Futibatinib: The First Covalent FGFR Kinase Inhibitor in Clinical Use.ACS medicinal chemistry letters · 2023Article
Corrections and comments
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Authors and funding
20 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fibroblast growth factor receptors (FGFR) 2 and 3 have been established as drivers of numerous types of cancer with multiple drugs approved or entering late stage clinical trials. A limitation of current inhibitors is vulnerability to gatekeeper resistance mutations. Using a combination of targeted high-throughput screening and structure-based drug design, we have developed a series of aminopyrazole based FGFR inhibitors that covalently target a cysteine residue on the P-loop of the kinase. The inhibitors show excellent activity against the wild-type and gatekeeper mutant versions of the enzymes. Further optimization using SAR analysis and structure-based drug design led to analogues with improved potency and drug metabolism and pharmacokinetics properties.
Identifiers
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Registered trials
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