ArticleThe Biochemical journal2019
Lessons from LIMK1 enzymology and their impact on inhibitor design.
Article in The Biochemical journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 28 citations in OpenAlex.
- Rational design and structural Bioinformatics-Driven discovery of tetrapeptide inhibitors for LIMK-Targeted cancer therapy.Medical oncology (Northwood, London, England) · 2025Article
- Computational Development of Allosteric Peptide Inhibitors Targeting LIM Kinases as a Novel Therapeutic Intervention.Cell biochemistry and biophysics · 2025Article
- Tetrahydropyrazolopyridinones as a Novel Class of Potent and Highly Selective LIMK Inhibitors.Journal of medicinal chemistry · 2025Article
- Covalent Targeting Leads to the Development of a LIMK1 Isoform-Selective Inhibitor.Journal of medicinal chemistry · 2025Article
- Discovery of MDI-114215: A Potent and Selective LIMK Inhibitor To Treat Fragile X Syndrome.Journal of medicinal chemistry · 2025Article
- Regulation and signaling of the LIM domain kinases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Distinct functional constraints driving conservation of the cofilin N-terminal regulatory tail.Nature communications · 2024Article
- LIM kinases in cardiovascular health and disease.Frontiers in physiology · 2024Review
- Autoregulation of the LIM kinases by their PDZ domain.Nature communications · 2023Article
- LIMK2: A Multifaceted kinase with pleiotropic roles in human physiology and pathologies.Cancer letters · 2023Review
- Comparative Analysis of Small-Molecule LIMK1/2 Inhibitors: Chemical Synthesis, Biochemistry, and Cellular Activity.Journal of medicinal chemistry · 2022Article
- Development and Characterization of Type I, Type II, and Type III LIM-Kinase Chemical Probes.Journal of medicinal chemistry · 2022Article
- LIM Kinases, Promising but Reluctant Therapeutic Targets: Chemistry and Preclinical Validation In Vivo.Cells · 2022Review
- Cytoskeletal dynamics regulates stromal invasion behavior of distinct liver cancer subtypes.Communications biology · 2022Article
- The Role of LIM Kinases during Development: A Lens to Get a Glimpse of Their Implication in Pathologies.Cells · 2022Review
- Review
- Progress in the therapeutic inhibition of Cdc42 signalling.Biochemical Society transactions · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
LIM domain kinase 1 (LIMK1) is a key regulator of actin dynamics. It is thereby a potential therapeutic target for the prevention of fragile X syndrome and amyotrophic lateral sclerosis. Herein, we use X-ray crystallography and activity assays to describe how LIMK1 accomplishes substrate specificity, to suggest a unique 'rock-and-poke' mechanism of catalysis and to explore the regulation of the kinase by activation loop phosphorylation. Based on these findings, a differential scanning fluorimetry assay and a RapidFire mass spectrometry activity assay were established, leading to the discovery and confirmation of a set of small-molecule LIMK1 inhibitors. Interestingly, several of the inhibitors were inactive towards the closely related isoform LIMK2. Finally, crystal structures of the LIMK1 kinase domain in complex with inhibitors (PF-477736 and staurosporine, respectively) are presented, providing insights into LIMK1 plasticity upon inhibitor binding.
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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.