DYRK1
Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) is a serine/threonine kinase that regulates neuronal differentiation, synaptic plasticity, and cell cycle progression[1][4]. Mechanistically, DYRK1A modulates pre- and post-synaptic signaling and alternative splicing, thereby influencing neuronal development and adult cognitive function[3][1]. DYRK1A activity affects cytoskeletal dynamics through MKL1-mediated pathways, promoting morphogenesis in human neonatal megakaryocytes[2]. Overexpression or dosage imbalance of DYRK1A contributes to neurodevelopmental disorders such as Down syndrome and MRD7, and to neurodegenerative diseases including Alzheimer’s and Parkinson’s disease[1][4][5]. Compared with related isoforms DYRK1B and DYRK2, DYRK1A uniquely regulates central nervous system processes, including tau phosphorylation and APP processing, while DYRK1B predominantly modulates stem cell behavior and metabolic pathways[1][6][7]. Pharmacologically, small molecule inhibitors such as harmine, AnnH75, and thiazoloquinazolines selectively target DYRK1A, enabling modulation of neuronal differentiation, alternative splicing, and pathological tau phosphorylation, with minimal off-target activity[3][4][6][8]. Agonists and inhibitors of DYRK1A also facilitate experimental studies of megakaryocyte morphogenesis, bipolar androgen therapy in prostate cancer, and CNS-related cellular senescence[2][9]. Structural studies reveal that inhibitor binding exploits ATP-competitive mechanisms and hinge region interactions, supporting development of isoform-selective chemical probes for translational research[8].
References:
- [1]. Arbones ML, et al. DYRK1A and cognition: A lifelong relationship. Pharmacol Ther. 2019 Feb;194:199-221. [Content Brief]
- [2]. Elagib KE, et al. Relieving DYRK1A repression of MKL1 confers an adult-like phenotype to human infantile megakaryocytes. J Clin Invest. 2022 Oct 3;132(19):e154839. [Content Brief]
- [3]. Rüben K, et al. Selectivity Profiling and Biological Activity of Novel β-Carbolines as Potent and Selective DYRK1 Kinase Inhibitors. PLoS One. 2015 Jul 20;10(7):e0132453. [Content Brief]
- [4]. Kargbo RB. Selective DYRK1A Inhibitor for the Treatment of Neurodegenerative Diseases: Alzheimer, et al. Selective DYRK1A Inhibitor for the Treatment of Neurodegenerative Diseases: Alzheimer, Parkinson, Huntington, and Down Syndrome. ACS Med Chem Lett. 2020 Jul 9;11(10):1795-1796. [Content Brief]
- [5]. Demuro S, et al. GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways. Int J Mol Sci. 2021 Aug 23;22(16):9098. [Content Brief]
- [6]. Foucourt A, et al. Design and synthesis of thiazolo[5,4-f]quinazolines as DYRK1A inhibitors, part II. Molecules. 2014 Sep 26;19(10):15411-39. [Content Brief]
- [7]. Kokkorakis N, et al. Minibrain-related kinase/dual-specificity tyrosine-regulated kinase 1B implication in stem/cancer stem cells biology. World J Stem Cells. 2020 Dec 26;12(12):1553-1575. [Content Brief]
- [8]. Kaltheuner IH, et al. Abemaciclib is a potent inhibitor of DYRK1A and HIP kinases involved in transcriptional regulation. Nat Commun. 2021 Nov 16;12(1):6607. [Content Brief]
- [9]. Atri Roozbahani G, et al. Induction of cellular senescence by androgen receptor agonist or antagonist is mediated via two novel common DYRK1A-DREAM and cyclin G2 signaling pathways in castration-resistant prostate cancer. J Adv Res. 2026 Feb;80:371-392. [Content Brief]
All Product Categories
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DYRK1 Related Products (64)
Related Products (64)
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CLK1-IN-3
0 ImagesCLK1-IN-3 (compound 10ad) is a potent and selective Clk1 inhibitor, with an IC50 of 5 nM and over 300-fold selectivity for Dyrk1A. CLK1-IN-3 also shows a relatively potent inhibition against Clk2 and Clk4, with IC50 values of 42 and 108 nM, respectively. CLK1-IN-3 potently induces autophagy in vitro. CLK1-IN-3 can be used for acute liver injury (ALI) research.
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ON 108600
0 ImagesSynonyms: 108600ON 108600 (108600) is a CK2 (CK2α1: IC50 = 50 nM; CK2α2 = 5 nM), TNIK (IC50 = 5 nM) and DYRK (DYRK1A: IC50 = 16 nM; DYRK1B = 7 nM; DYRK2: = 28 nM). ON 108600 suppresses the growth of CD44high/CD24low breast cancer stem cell (BCSC) populations, induces G2/M arrest and apoptosis in triple negative breast cancer (TNBC) cells, and inhibits tubulin polymerization. ON 108600 can be used for the study of chemotherapy-resistant and metastatic TNBC.
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GNF2133 hydrochloride
0 ImagesGNF2133 hydrochloride is a potent, selective and orally active DYRK1A inhibitor with IC50s of 0.0062, >50 µM for DYRK1A and GSK3β, respectively. GNF2133 hydrochloride shows good proliferation potency and efficacy on rat and human primary β-cell. GNF2133 hydrochloride significantly improves glucose disposal capacity and increases insulin secretion. GNF2133 hydrochloride has the potential for the research of type 1 diabetes.
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ZJCK-6-46
0 ImagesZJCK-6-46 (32) is a potential and orally activeDYRK1A inhibitor (IC50 = 0.68 nM) with high BBB permeability (CNS+). ZJCK-6-46 (32) reduces tau phosphorylation. ZJCK-6-46 (32) ameliorates cognitive dysfunction by obviously reducing the expression of phosphorylated tau and neuronal loss in vivo.
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DS12881479
0 ImagesDS12881479 is a selective non-ATP-competitive MNK1 inhibitor with an IC50 value of 387 nM. DS12881479 stabilizes MNK1 in its autoinhibited DFD-out conformation, blocks eIF4E phosphorylation, suppresses tumor cell proliferation and induces weak apoptosis. DS12881479 also inhibits FLT3 and DYRK1a kinase activity at high concentrations. DS12881479 can be used for the research of cancer, such as leukemia.
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DYRK2-IN-2
0 ImagesCat. No.: HY-402805CAS No.: 2416195-65-6DYRK2-IN-2 (Compound C17) is a selective inhibitor of DYRK2, with its IC50 value being 40.3 nM. The inhibitory activity of DYRK2-IN-2 on DYRK1A (IC50 = 1842 nM), DYRK1B (IC50 = 1335 nM), DYRK4 (IC50 = 1931 nM), DYRK3 (IC50 = 112 nM), and CLKs (IC50 = 540-6496 NM) is relatively low. DYRK2-IN-2 inhibits the phosphorylation of Tau protein at Thr212 and shows moderate cytotoxicity in HT22 cells. DYRK2-IN-2 can be used in cancer research.
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Dyrk1A-IN-13
0 ImagesCat. No.: HY-176402Purity: 99.43%Dyrk1A-IN-13 (Compound 1) is a DYRK1A inhibitor (IC50: 41 nM). Dyrk1A-IN-13 reduces LPS-induced NO production and has antioxidant and anti-inflammatory activities. Dyrk1A-IN-13 can be used in the research of Alzheimer's disease, cancer and diabetes.
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AO-365/43472821
0 ImagesAO-365/43472821 is a selective, brain-penetrant Dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) inhibitor (IC50 = 0.29 μM) and shows a significant inhibitory effect on (CDC-like kinase 1) CLK1 (IC50 = 0.08 μM). AO-365/43472821 could protect the human neuroblastoma cell line SH-SY5Y from Okadaic acid (HY-N6785) (OA)-induced injury. AO-365/43472821 decreased tau (pSer396)/tau and Aβ1-42 protein expression. AO-365/43472821 can be used for the study of Alzheimer's disease.
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(R)-(+)-O-Demethylbuchenavianine
0 Images(R)-(+)-O-Demethylbuchenavianine is an inhibitor for Cyclin-dependent kinases (CDK). (R)-(+)-O-Demethylbuchenavianine inhibits CDK1, CDK5, glycogen synthase kinase-3 (GSK3), cdc2-like kinase (CLK1) and dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A), with IC50s of 1.1, 0.95, >10, >10 and >10 μM, respectively.
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MBM-55S
0 ImagesCat. No.: HY-101029ACAS No.: 2083624-07-9MBM-55S is a potent NIMA-related kinase 2 (Nek2) inhibitor with an IC50 of 1 nM. MBM-55S shows a 20-fold or greater selectivity in most kinases with the exception of RSK1 (IC50=5.4 nM) and DYRK1a (IC50=6.5 nM). MBM-55S effectively inhibits the proliferation of cancer cells by inducing cell cycle arrest and apoptosis. MBM-55S shows antitumor activities, and no obvious toxicity to mice.
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Dyrk1A/B-IN-1
0 ImagesCat. No.: HY-146337CAS No.: 3032401-50-3Dyrk1A/B-IN-1 (compound 3n) is a potent, selective and cell-permeable DYRK1A and DYRK1B inhibitor with Kis of 67.8 nM and 237.9 nM, and IC50s of 1.1 μM and 0.8 μM, respectively. Dyrk1A/B-IN-1 is not toxic to human cells. Dyrk1A/B-IN-1 can be used for researching DYRK1A and DYRK1B cellular functions and their role in pathologies.
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Haspin-IN-2
0 ImagesCat. No.: HY-146587CAS No.: 2768474-47-9
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VS-II-173
0 ImagesCat. No.: HY-122670CAS No.: 1627962-21-3VS-II-173 is a pan-Pim kinase inhibitor with IC50 values of 0.07 μM and 0.02 μM for Pim1 and Pim3, respectively, and a residual activity of 46% for Pim2 at 1 μM. VS-II-173 also inhibits kinases such as HIPK2, PRK2, RSK1, DYRK1a and AMPKα1, selectively inhibiting acute myeloid leukemia (AML) cells with significantly lower toxicity to non-malignant cells (EC50 > 30 μM). VS-II-173 weakens the phosphorylation of substrates such as Stat5 (Y694), MDM2 (S166), Bad (S112), and 4E-BP1 (T37/46) by inhibiting Pim kinase-mediated signaling pathways, blocking pro-survival signals in AML cells and inducing apoptosis. VS-II-173 synergistically enhances anti-AML activity when combined with Daunorubicin (HY-13062A). VS-II-173 can be used in AML research, especially for AML with FLT3-ITD mutations and NPM1 mutations .
