ArticleScientific reports2018
DYRK1A inhibition and cognitive rescue in a Down syndrome mouse model are induced by new fluoro-DANDY derivatives.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 69 citations in OpenAlex.
- Targeting DYRK1A with rationally designed pyrazine-guanidine hybrids for Alzheimer's disease: design, synthesis, and biological evaluation.RSC advances · 2026Article
- 7-azaindole as privileged scaffold: Advances in drug design and structural modification.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- A Polypharmacology-Driven Approach to Alzheimer's Disease and Tauopathies: Rational Design, Synthesis and Characterization of Amino-Pyrazole-Based Multikinase (GSK-3β/FYN-α/DYRK1A) Inhibitors.Journal of medicinal chemistry · 2026Article
- Article
- Targeting dual specificity tyrosine-phosphorylation-regulated kinase 1A mitigates tauopathy and enhances recovery after repetitive head injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Interferon signaling modulates Down syndrome-associated Alzheimer's disease pathology in a mouse model.iScience · 2025Article
- Discovery of Dietary Plant Flavonols as Novel Potent Inhibitors Targeting DYRK1A Kinase.Biomolecules · 2025Article
- Cholinergic System Structure and Function Changes in Individuals with Down Syndrome During the Development of Alzheimer's Disease.Current topics in behavioral neurosciences · 2025Review
- Network Pharmacology Identifies Intersection Genes of Apigenin and Naringenin in Down Syndrome as Potential Therapeutic Targets.Pharmaceuticals (Basel, Switzerland) · 2024Article
- The Role of Tau Pathology in Alzheimer's Disease and Down Syndrome.Journal of clinical medicine · 2024Review
- Association of genetic variants with autism spectrum disorder in Japanese children revealed by targeted sequencing.Frontiers in genetics · 2024Article
- Binding mechanism and biological effects of flavone DYRK1A inhibitors for the design of new antidiabetics.Scientific reports · 2023Article
- Ts66Yah, a mouse model of Down syndrome with improved construct and face validity.Disease models & mechanisms · 2022Article
- The Omnipresence of DYRK1A in Human Diseases.International journal of molecular sciences · 2022Review
- Genetic Mapping of APP and Amyloid-β Biology Modulation by Trisomy 21.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2022Article
- Selective Macrocyclic Inhibitors of DYRK1A/B.ACS medicinal chemistry letters · 2022Article
- Rational Design and Identification of Harmine-Inspired, N-Heterocyclic DYRK1A Inhibitors Employing a Functional Genomic In Vivo Drosophila Model System.ChemMedChem · 2022Article
- New insights into the regulation ofFrontiers in neuroscience · 2022Article
- Review
- Restoring neuronal chloride homeostasis with anti-NKCC1 gene therapy rescues cognitive deficits in a mouse model of Down syndrome.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
Corrections and comments
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inhibition of DYRK1A kinase, produced by chromosome 21 and consequently overproduced in trisomy 21 subjects, has been suggested as a therapeutic approach to treating the cognitive deficiencies observed in Down syndrome (DS). We now report the synthesis and potent DYRK1A inhibitory activities of fluoro derivatives of 3,5-di(polyhydroxyaryl)-7-azaindoles (F-DANDYs). One of these compounds (3-(4-fluorophenyl)-5-(3,4-dihydroxyphenyl)-1H-pyrrolo[2,3-b]pyridine, 5a) was selected for in vivo studies of cognitive rescuing effects in a standard mouse model of DS (Ts65Dn line). Using the Morris water maze task, Ts65Dn mice treated i.p. with 20 mg/kg of 5a performed significantly better than Ts65Dn mice treated with placebo, confirming the promnesiant effect of 5a in the trisomic mice. Overall, these results demonstrate for the first time that selective and competitive inhibition of DYRK1A kinase by the F-DANDY derivative 5a may provide a viable treatment strategy for combating the memory and learning deficiencies encountered in DS.
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