ArticleACS pharmacology & translational science2026
Mapping the Brain Interaction Network of the Dual-Specificity, Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A) Targeted by Leucettinib-21 Using Affinity Chromatography.
Article in ACS pharmacology & translational science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Leucettinib-21 decreases dosage effects of DYRK1A in human trisomy 21 induced pluripotent stem cell-derived neural cells.Disease models & mechanisms · 2026Article
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10 authors.
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Abstract
Leucettinibs are substituted 2-aminoimidazolin-4-ones inspired by the marine sponge natural product Leucettamine B and developed as pharmacological inhibitors of DYRK1A (dual-specificity, tyrosine phosphorylation-regulated kinase 1A), a therapeutic target for indications such as Down syndrome, Alzheimer's disease, Parkinson's disease, diabetes, myocardial infarction, etc. Leucettinib-21 is currently being tested in a phase 1 clinical trial. In this study, four different affinity chromatography-based approaches were developed to identify the rat brain targets of Leucettinib-21: (1) Leucettinib-21 (and its kinase-inactive isomer as control) immobilized on agarose beads, (2) immobilized metal affinity chromatography, (3) KinAffinity bead competition assays, and (4) immunoprecipitation with DYRK1A-specific antibodies. Altogether, these complementary methods (1) confirm known targets of Leucettinib-21, and identify (2) new protein kinases and nonkinases interacting with Leucettinib-21, (3) potential new partners of DYRK1A, and (4) pathways and cellular mechanisms potentially modulated by Leucettinib-21. These methods can be expanded to various cells and tissues from models of pathologies where Leucettinib-21 demonstrates efficacy.
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