Ask about this productRelated genes to: Dyrk1a antibody
- Gene:
- DYRK1A NIH gene
- Name:
- dual specificity tyrosine phosphorylation regulated kinase 1A
- Previous symbol:
- DYRK1, DYRK, MNBH
- Synonyms:
- -
- Chromosome:
- 21q22.13
- Locus Type:
- gene with protein product
- Date approved:
- 1999-01-29
- Date modifiied:
- 2016-02-12
Related products to: Dyrk1a antibody
Related articles to: Dyrk1a antibody
- Pulmonary hypertension (PH) is a progressive disorder marked by elevated pulmonary artery (PA) pressure and vascular remodeling, often leading to right heart failure. A key feature is pulmonary artery smooth muscle cells (PASMC) phenotypic switching from a contractile to a synthetic state, which drives medial hypertrophy and vascular occlusion. However, the role of DYRK1A in this process remains unclear. - Source: PubMed
Publication date: 2026/09/08
Dong ZhengweiLu QianqianXue ZhifengLi YongLi LanZhao HuanQin XiaoyaoJiao ZhiangZhan ChunmiaoDeng HaoHe QingyongLi ShuijieZhu MingjunZhang JianFan Guanwei - This study investigates the mechanisms of ZDWX-25, a novel dual DYRK1A/GSK3β inhibitor, in alleviating tau pathology and explores its potential anti-neuroinflammatory effects. - Source: PubMed
Publication date: 2026/08/27
Wang WeiyiXing YuXu ZongheLiu SiyuanZhou LijunNing XinyueLi XinzhuZheng FangyuanYang AizhuLi ZhenshuRen MengyuXu ZihuaZhao Qingchun - Neurodegenerative disorders are increasing in prevalence, yet disease-modifying therapies remain limited. Dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) phosphorylates tau and regulates inflammatory signaling, making it a potential therapeutic target for neurodegenerative diseases. To investigate the relevance of DYRK1A to primary tauopathies, we first evaluated DYRK1A protein levels in the superior frontal gyrus of individuals with Pick's disease, corticobasal degeneration, and progressive supranuclear palsy. DYRK1A protein expression was significantly elevated in individuals with primary tauopathies compared with healthy controls and positively correlated with Braak stage. Conversely, DYRK1A levels inversely correlated with last Mini-Mental State Examination (MMSE) scores and brain weight, linking elevated DYRK1A expression to disease severity. We next developed DYR533, a selective, orally bioavailable, brain-penetrant small-molecule DYRK1A inhibitor with an S(35) score of 1.4 nM based on a 403-target KINOMEscan assay. Mechanistically, DYR533 prevented the autophosphorylation of newly translated DYRK1A, rendering the kinase inactive and thereby inhibiting phosphorylation of downstream substrates. We next evaluated the therapeutic efficacy of DYR533 in the PS19 mouse model of primary tauopathy, assessing tau hyperphosphorylation, neuroinflammation, motor function, and spatial cognition. DYR533 reduced tau hyperphosphorylation at threonine 217, threonine 181, and serine 396, and attenuated the expression of neuroinflammatory cytokines and chemokines implicated in disease progression. In PS19 mice, DYR533 treatment produced modest improvements on behavior. Together, these findings establish an association between elevated DYRK1A and disease severity in human primary tauopathies and demonstrate that pharmacological inhibition of DYRK1A with DYR533 reduces pathological tau phosphorylation and neuroinflammatory signaling in vivo. - Source: PubMed
Publication date: 2026/08/25
Velazquez RamonBartholomew SamanthaWinslow WendyTallino SavannahFoley ChristopherShaw YengRokey SamanthaJudd JessicaBeach ThomasSerrano GeidyWilms GerritKushwahag RaginiMcMahon AidanGinn SeanBecker WalterHulme ChristopherDunckley Travis - DYRK1A kinase is a multifunctional enzyme involved in cellular homeostasis and signaling regulation, and its dysregulation is associated with various diseases, including neurological disorders. In this study, a 3D-QSAR model was developed using the experimentally determined inhibitory values of 30 potent compounds. The model exhibited strong statistical performance (Q² = 0.504, R² = 0.996, R² = 0.659), which was further validated by a high R² value (0.936), a significant F-value (≈569.14), a high bootstrap coefficient (R² = 0.995), Williams plot analysis, and Y-randomization testing. 3D-QSAR contour analysis and the enzyme surface electrostatic potential map confirmed favorable compound alignment in the active site. Guided by the model's contour maps, 138,651 novel inhibitors were designed via appropriate substitutions at key positions. After comprehensive screening, including pIC₅₀ prediction via the 3D-QSAR model, drug-likeness evaluation, and Lipinski's Rule of Five, 756 compounds were selected for molecular docking. The novel compounds exhibited higher binding affinity and stronger interactions with Lys188 and Asp307 compared to the dataset compounds. The top five compounds with binding energies between -16.706 and -17.193 kcal/mol were selected for further analysis with 400 ns molecular dynamics simulations. RMSD values below 0.5 nm, low RMSF, stable hydrogen bonds, and consistent SASA profiles indicated the structural stability of all complexes. PBSA and GBSA binding free energy calculations yielded values of -14.980 to -37.380 and -30.320 to -45.640 kcal/mol, respectively, indicating strong ligand-receptor interactions. Comprehensive QTAIM and IGMH analyses provided further insight into the nature and strength of intermolecular interactions. - Source: PubMed
Publication date: 2026/08/29
Mehrparvar MahlaEbrahimi AliMostafavi Najmeh - Diabetes mellitus results from inadequate pancreatic β-cell mass or function, whereas mature β-cells are generally incapable of spontaneous proliferation. Therefore, promoting β-cell proliferation could be an approach toward diabetes interventions. Over the past decades, dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) has emerged as a key negative regulator of β-cell proliferation via modulating the NFAT signaling pathway and DREAM complex assembly, thereby establishing DYRK1A as a promising therapeutic target for diabetes. In this minireview, we provide an overview of recent progress (2018-2025) in medicinal chemistry toward small-molecule DYRK1A inhibitors for β-cell regeneration. Particular attention is paid to scaffold design, Structure-Activity Relationship (SAR) analysis, and structure-based optimization of representative compounds. We systematically discuss the structural modifications and biological evaluation of natural product-derived scaffolds (such as β-carboline harmine and its analogues, xanthone desmethylbellidifolin) and synthetic scaffolds (including aminopyrazine, 6-azaindole, 1,5- naphthyridine and 1,3,4-thiadiazine), as well as their proliferative effects on human β-cells in vitro and in vivo. Additionally, we highlight medicinal chemistry strategies aimed at improving DYRK1A selectivity, reducing off-target effects, and uncoupling pro-proliferative activity from cytotoxicity. Finally, this review outlines the current challenges and future prospects for the rational design of potent, selective, and β-cell-targeted DYRK1A inhibitors from a medicinal chemistry perspective. - Source: PubMed
Publication date: 2026/08/06
Zhou HaishanWang YanBai JuanWang Yang