ArticlePloS one2014
Design and synthesis of a library of lead-like 2,4-bisheterocyclic substituted thiophenes as selective Dyrk/Clk inhibitors.
Article in PloS one, 2014. 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, 61 citations in OpenAlex.
- Exploring Thiophene Derivatives: Synthesis Strategies and Biological Significance.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- New thiophene derivatives: chemoselective synthesis, antitumor effectiveness, structural characterization, DFT calculations, Hirshfeld surface, and Fukui function analysis.BMC chemistry · 2024Article
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- Mirk/Dyrk1B Kinase Inhibitors in Targeted Cancer Therapy.Pharmaceutics · 2024Review
- Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity.Future medicinal chemistry · 2024Article
- Cdc2-like kinases: structure, biological function, and therapeutic targets for diseases.Signal transduction and targeted therapy · 2023Review
- Quiescent Cancer Cells-A Potential Therapeutic Target to Overcome Tumor Resistance and Relapse.International journal of molecular sciences · 2023Review
- Synthesis, Molecular Docking Study, and Cytotoxic Activity against MCF Cells of New Thiazole-Thiophene Scaffolds.Molecules (Basel, Switzerland) · 2022Article
- Synthesis, and docking studies of novel heterocycles incorporating the indazolylthiazole moiety as antimicrobial and anticancer agents.Scientific reports · 2022Article
- DYRK1A activates NFATC1 to increase glioblastoma migration.Cancer medicine · 2021Article
- 5-Methoxybenzothiophene-2-Carboxamides as Inhibitors of Clk1/4: Optimization of Selectivity and Cellular Potency.Molecules (Basel, Switzerland) · 2021Article
- Minibrain-related kinase/dual-specificity tyrosine-regulated kinase 1B implication in stem/cancer stem cells biology.World journal of stem cells · 2020Review
- Cdc-Like Kinases (CLKs): Biology, Chemical Probes, and Therapeutic Potential.International journal of molecular sciences · 2020Review
- How to design potent and selective DYRK1B inhibitors? Molecular modeling study.Journal of molecular modeling · 2019Article
- 10-iodo-11H-indolo[3,2-c]quinoline-6-carboxylic acids are selective inhibitors of DYRK1A.Journal of medicinal chemistry · 2015Article
- Splicing Regulators and Their Roles in Cancer Biology and Therapy.BioMed research international · 2015Review
- Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors.PloS one · 2015Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Dyrk family of protein kinases is implicated in the pathogenesis of several diseases, including cancer and neurodegeneration. Pharmacological inhibitors were mainly described for Dyrk1A so far, but in fewer cases for Dyrk1B, Dyrk2 or other isoforms. Herein, we report the development and optimization of 2,4-bisheterocyclic substituted thiophenes as a novel class of Dyrk inhibitors. The optimized hit compounds displayed favorable pharmacokinetic properties and high ligand efficiencies, and inhibited Dyrk1B in intact cells. In a larger selectivity screen, only Clk1 and Clk4 were identified as additional targets of compound 48, but no other kinases frequently reported as off-targets. Interestingly, Dyrk1A is implicated in the regulation of alternative splicing, a function shared with Clk1/Clk4; thus, some of the dual inhibitors might be useful as efficient splicing modulators. A further compound (29) inhibited Dyrk1A and 1B with an IC50 of 130 nM, showing a moderate selectivity over Dyrk2. Since penetration of the central nervous system (CNS) seems possible based on the physicochemical properties, this compound might serve as a lead for the development of potential therapeutic agents against glioblastoma. Furthermore, an inhibitor selective for Dyrk2 (24) was also identified, which might be are suitable as a pharmacological tool to dissect Dyrk2 isoform-mediated functions.
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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.