ArticleMedChemComm2017
Approaches to selective fibroblast growth factor receptor 4 inhibition through targeting the ATP-pocket middle-hinge region.
Article in MedChemComm, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 39 citations in OpenAlex.
- A FRET-Based Assay for Assessing Covalent Warhead Reactivity.ACS omega · 2026Article
- Tunable Aromatic Sulfoxides and Sulfones as Cysteine-Targeting Warheads: Exploring the Structure-Reactivity Relationship.Journal of medicinal chemistry · 2026Article
- Advances in reversible covalent kinase inhibitors.Medicinal research reviews · 2025Review
- Discovery of electrophilic degraders that exploit SbioRxiv : the preprint server for biology · 2024Article
- Exploring 2-Sulfonylpyrimidine Warheads as Acrylamide Surrogates for Targeted Covalent Inhibition: A BTK Story.Journal of medicinal chemistry · 2024Article
- Substitution-Induced Mechanistic Switching in SMolecules (Basel, Switzerland) · 2024Article
- Vinylpyridine as a Tunable Covalent Warhead Targeting C797 in EGFR.ACS medicinal chemistry letters · 2024Article
- Discovery and Characterization of a Novel Series of Chloropyrimidines as Covalent Inhibitors of the Kinase MSK1.ACS medicinal chemistry letters · 2022Article
- Signaling Pathway and Small-Molecule Drug Discovery of FGFR: A Comprehensive Review.Frontiers in chemistry · 2022Review
- Discovery of a Potent and Highly Isoform-Selective Inhibitor of the Neglected Ribosomal Protein S6 Kinase Beta 2 (S6K2).Cancers · 2021Article
- Investigation of Covalent Warheads in the Design of 2-Aminopyrimidine-based FGFR4 Inhibitors.ACS medicinal chemistry letters · 2021Article
- Rotational Freedom, Steric Hindrance, and Protein Dynamics Explain BLU554 Selectivity for the Hinge Cysteine of FGFR4.ACS medicinal chemistry letters · 2019Article
- Review
- 2-Formylpyridyl Ureas as Highly Selective Reversible-Covalent Inhibitors of Fibroblast Growth Factor Receptor 4.ACS medicinal chemistry letters · 2018Article
Corrections and comments
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Authors and funding
15 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A diverse range of selective FGFR4 inhibitor hit series were identified using unbiased screening approaches and by the modification of known kinase inhibitor scaffolds. In each case the origin of the selectivity was consistent with an interaction with a poorly conserved cysteine residue within the middle-hinge region of the kinase domain of FGFR4, at position 552. Targeting this region identified a non-covalent diaminopyrimidine series differentiating by size, an irreversible-covalent inhibitor in which Cys552 undergoes an SNAr reaction with a 2-chloropyridine, and a reversible-covalent inhibitor series in which Cys552 forms a hemithioacetal adduct with a 2-formyl naphthalene. In addition, the introduction of an acrylamide into a known FGFR scaffold identified a pan-FGFR inhibitor which reacted with both Cys552 and a second poorly conserved cysteine on the P-loop of FGFR4 at position 477 which is present in all four FGFR family members.
Identifiers
What OpenQuestion holds
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.