DYRK1B

Summary

DYRK1B (dual specificity tyrosine phosphorylation regulated kinase 1B, HGNC:3092) is a protein-coding gene on chromosome 19q13.2, encoding Dual specificity tyrosine-phosphorylation-regulated kinase 1B (Q9Y463). Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities.

This gene encodes a member of a family of nuclear-localized protein kinases. The encoded protein participates in the regulation of the cell cycle. Expression of this gene may be altered in tumor cells, and mutations in this gene were found to cause abdominal obesity-metabolic syndrome 3. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 9149 — RefSeq curated summary.

At a glance

• Gene–disease (curated): abdominal obesity-metabolic syndrome 3 (Strong, GenCC)
• GWAS associations: 1
• Clinical variants (ClinVar): 361 total — 2 pathogenic
• Phenotypes (HPO): 14
• Druggable target: yes — 35 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_004714

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3092
Approved symbol	DYRK1B
Name	dual specificity tyrosine phosphorylation regulated kinase 1B
Location	19q13.2
Locus type	gene with protein product
Status	Approved
Aliases	MIRK
Ensembl gene	ENSG00000105204
Ensembl biotype	protein_coding
OMIM	604556
Entrez	9149

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 7 protein_coding, 1 retained_intron

ENST00000323039, ENST00000348817, ENST00000430012, ENST00000593685, ENST00000597639, ENST00000600611, ENST00000601696, ENST00000601972

RefSeq mRNA: 3 — MANE Select: NM_004714 NM_004714, NM_006483, NM_006484

CCDS: CCDS12543, CCDS12544, CCDS46075

Canonical transcript exons

ENST00000323039 — 11 exons

Exon	Start	End
ENSE00000706171	39830664	39830783
ENSE00000706176	39830375	39830563
ENSE00000706179	39829880	39830027
ENSE00000706187	39826180	39826286
ENSE00000877636	39827510	39827656
ENSE00000877638	39827285	39827425
ENSE00000877640	39826672	39826987
ENSE00002509144	39828297	39828583
ENSE00003148162	39825350	39826086
ENSE00003844528	39834023	39834162
ENSE00003993921	39831805	39831968

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 13.5942 / max 146.7384, expressed in 1669 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
180911	11.8779	1650
180909	0.5526	249
180910	0.5044	283
180907	0.2016	58
180908	0.1711	75
180906	0.1538	68
180904	0.0779	19
180905	0.0550	24

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	96.93	gold quality
skeletal muscle tissue	UBERON:0001134	96.56	gold quality
right testis	UBERON:0004534	96.18	gold quality
left testis	UBERON:0004533	96.07	gold quality
gastrocnemius	UBERON:0001388	95.85	gold quality
testis	UBERON:0000473	95.46	gold quality
muscle of leg	UBERON:0001383	95.35	gold quality
muscle tissue	UBERON:0002385	92.05	gold quality
right uterine tube	UBERON:0001302	89.82	gold quality
pituitary gland	UBERON:0000007	89.81	gold quality
right adrenal gland	UBERON:0001233	89.14	gold quality
adenohypophysis	UBERON:0002196	88.88	gold quality
right adrenal gland cortex	UBERON:0035827	88.71	gold quality
apex of heart	UBERON:0002098	88.49	gold quality
prefrontal cortex	UBERON:0000451	87.76	gold quality
stromal cell of endometrium	CL:0002255	87.62	gold quality
frontal cortex	UBERON:0001870	87.38	gold quality
granulocyte	CL:0000094	87.16	gold quality
blood	UBERON:0000178	86.93	gold quality
right frontal lobe	UBERON:0002810	86.84	gold quality
superior frontal gyrus	UBERON:0002661	86.82	gold quality
cortex of kidney	UBERON:0001225	86.23	gold quality
primary visual cortex	UBERON:0002436	86.16	gold quality
cerebral cortex	UBERON:0000956	85.86	gold quality
nucleus accumbens	UBERON:0001882	85.79	gold quality
left adrenal gland	UBERON:0001234	85.74	gold quality
heart left ventricle	UBERON:0002084	85.64	gold quality
anterior cingulate cortex	UBERON:0009835	85.48	gold quality
left adrenal gland cortex	UBERON:0035825	85.33	gold quality
brain	UBERON:0000955	85.29	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-GEOD-99795	no	11.72
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

miRNA regulators (miRDB)

69 targeting DYRK1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-1296-3P	99.72	64.04	636
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-646	99.68	67.84	1645
HSA-MIR-3175	99.65	66.30	2031

Literature-anchored findings (GeneRIF, showing 33)

• activation by MKK2 and role as transcriptional activator of HNF1alpha (PMID:11980910)
• p38 MAP Kinase suppresses the function of Mirk as a transcriptional activator only when cells are proliferating (PMID:12384504)
• Mirk is anti-apoptotic in myoblasts (PMID:15851482)
• Mirk is a survival factor for pancreatic ductal adenocarcinoma. Because knockout of Mirk does not cause embryonic lethality, Mirk is not essential for normal cell growth. (PMID:16618736)
• This review summarizes the known regulators and functions of Mirk kinase and outlines opportunities for future studies of Mirk in the fields of muscle and tumor biology. (PMID:16845176)
• GSK-3beta but also DYRK1B modulates cyclin D1 subcellular localization by the phosphorylation of Thr(288). These results suggest that DIF-3 induces degradation of cyclin D1 through the GSK-3beta- and DYRK1B-mediated threonine phosphorylation in HeLa cells (PMID:17046823)
• BCL2 and BCL-xL facilitation of G0 quiescence requires BAX, BAK, and p27 phosphorylation by Mirk (PMID:18818203)
• Quiescent pancreatic cancer cells depleted of Mirk became less viable because they were damaged by ROS, and had increased levels of G(1) cyclins to prime cells to escape quiescence. (PMID:19351855)
• Mirk, through regulating cyclin D turnover, and the CDK inhibitor p27, as shown by depletion studies, functioned independently and additively to regulate the exit of tumor cells from quiescence. (PMID:19542220)
• the kinase Mirk is essential for the growth and survival of osteosarcoma cells. (PMID:20042639)
• In line with a redirection of autocrine toward paracrine HH signaling by a KRAS-DYRK1B network, we find high levels of GLI1 expression restricted to the stromal compartment and not to SHH-expressing tumor cells in pancreatic adenocarcinoma. (PMID:20512148)
• Mirk/Dyrk1B plays an important role in ovarian cancer cell survival through modulating FoxO translocation. (PMID:22159921)
• DYRK1B is a novel Thr(286)-CCND1 kinase that acts independently of GSK3beta to promote CCND1 degradation. (PMID:24134204)
• Upregulation of Mirk mRNA expression is mediated by CREB binding to two sites in the Mirk promoter upstream of the transcription start site and one site within exon 4. (PMID:24590896)
• A founder mutation was identified in DYRK1B, substituting cysteine for arginine at position 102 in 3 families with metabolic syndrome. (PMID:24827035)
• Data reveal a novel role for miR-9 in regulation of the NFAT pathway by targeting KPNB1 and DYRK1B. (PMID:25696812)
• NKX3.1 and DYRK1B were shown to interact via the DYRK1B kinase domain. In vitro kinase assay showed that DYRK1B phosphorylated NKX3.1 at serine 185, a residue critical for NKX3.1 steady-state turnover. (PMID:25777618)
• The study shows that DYRK1B is a novel ERK2 substrate, uncovering new links between two kinases involved in cell fate decisions. (PMID:26346493)
• High DYRK1B expression is associated with pancreatic and skin cancers. (PMID:26784250)
• Dyrk1B was overexpressed in breast cancer tissues and cells and correlates with FoxO1 phosphorylation and cell proliferation. (PMID:28554575)
• DYRK1B mutations associated with metabolic syndrome interfere with the maturation of DYRK1B by tyrosine autophosphorylation and compromise the conformational stability of the catalytic domain, which renders the kinase susceptible to misfolding. (PMID:28743892)
• Through the activation of DYRK1B, Hedgehog signaling facilitates microtubule-dependent processes such as intracellular mitochondrial transport, mesenchymal cell polarization or directed cell migration. (PMID:30317528)
• DCAF7/WDR68 is required for normal levels of DYRK1A and DYRK1B (PMID:30496304)
• Human cytomegalovirus(HCMV) modulates cellular dual specificity tyrosine phosphorylation regulated kinase 1B (DYRK1B) during placental replication which may have implications for congenital HCMV pathogenesis and represent promising antiviral targets. (PMID:30501876)
• Screen identifies DYRK1B network as mediator of transcription repression on damaged chromatin. (PMID:32611815)
• Proline Hydroxylation Primes Protein Kinases for Autophosphorylation and Activation. (PMID:32640193)
• Study of DYRK1B gene expression and its association with metabolic syndrome in a small cohort of Egyptians. (PMID:34291393)
• Suppression of DYRK1A/B Drives Endoplasmic Reticulum Stress-mediated Autophagic Cell Death Through Metabolic Reprogramming in Colorectal Cancer Cells. (PMID:34969768)
• Differential maturation and chaperone dependence of the paralogous protein kinases DYRK1A and DYRK1B. (PMID:35165364)
• DYRK1B-STAT3 Drives Cardiac Hypertrophy and Heart Failure by Impairing Mitochondrial Bioenergetics. (PMID:35235343)
• Analysis of DYRK1B, PPARG, and CEBPB Expression Patterns in Adipose-Derived Stem Cells from Patients Carrying DYRK1B R102C and Healthy Individuals During Adipogenesis. (PMID:36318489)
• Targeting the survival kinase DYRK1B: A novel approach to overcome radiotherapy-related treatment resistance. (PMID:38040123)
• Pathogenic, Total Loss-of-Function DYRK1B Variants Cause Monogenic Obesity Associated With Type 2 Diabetes. (PMID:38170957)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	dyrk1b	ENSDARG00000070187
mus_musculus	Dyrk1b	ENSMUSG00000002409
rattus_norvegicus	Dyrk1b	ENSRNOG00000019254
drosophila_melanogaster	mnb	FBGN0259168
caenorhabditis_elegans		WBGENE00003149
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), HIPK3 (ENSG00000110422), CLK4 (ENSG00000113240), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK2 (ENSG00000176444), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Dual specificity tyrosine-phosphorylation-regulated kinase 1B — Q9Y463 (reviewed: Q9Y463)

Alternative names: Minibrain-related kinase, Mirk protein kinase

All UniProt accessions (4): A0A9H4CVU7, Q9Y463, M0R131, M0R2X3

UniProt curated annotations — full annotation on UniProt →

Function. Dual-specificity kinase which possesses both serine/threonine and tyrosine kinase activities. Plays an essential role in ribosomal DNA (rDNA) double-strand break repair and rDNA copy number maintenance. During DNA damage, mediates transcription silencing in part via phosphorylating and enforcing DSB accumulation of the histone methyltransferase EHMT2. Enhances the transcriptional activity of TCF1/HNF1A and FOXO1. Inhibits epithelial cell migration. Mediates colon carcinoma cell survival in mitogen-poor environments. Inhibits the SHH and WNT1 pathways, thereby enhancing adipogenesis. In addition, promotes expression of the gluconeogenic enzyme glucose-6-phosphatase catalytic subunit 1 (G6PC1).

Subunit / interactions. Dimer. Interacts with DCOHM, MAP2K3/MKK3, RANBP9 and TCF1/HNF1A. Part of a complex consisting of RANBP9, RAN, DYRK1B and COPS5. Interacts with DCAF7. Interacts with RNF169.

Subcellular location. Nucleus. Nucleolus. Chromosome.

Tissue specificity. Highest expression in skeletal muscle, testis, heart and brain with little expression in colon or lung. Expressed in a variety of tumor cell lines.

Post-translational modifications. Autophosphorylated on tyrosine residues. Phosphorylated by MAP kinase. Tyrosine phosphorylation may be required for dimerization.

Disease relevance. Abdominal obesity-metabolic syndrome 3 (AOMS3) [MIM:615812] A form of abdominal obesity-metabolic syndrome, a disorder characterized by abdominal obesity, high triglycerides, low levels of high density lipoprotein cholesterol, high blood pressure, and elevated fasting glucose levels. AOMS3 is characterized by early-onset coronary artery disease, central obesity, hypertension, and diabetes. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Inhibited by RANBP9.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. MNB/DYRK subfamily.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y463-1	1	yes
Q9Y463-2	2
Q9Y463-3	3

RefSeq proteins (3): NP_004705, NP_006474, NP_006475 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR044131	PKc_DYR1A/1B	Domain
IPR050494	Ser_Thr_dual-spec_kinase	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.12.1 — dual-specificity kinase (BRENDA: 51 organisms, 125 substrates, 188 inhibitors, 14 Km, 10 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.019–0.1185	7
HISTONE H1	0.006–0.012	5

Catalyzed reactions (Rhea), 3 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)
• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (66 total): helix 14, modified residue 10, strand 9, sequence variant 6, turn 6, compositionally biased region 4, region of interest 4, mutagenesis site 4, binding site 3, splice variant 2, chain 1, domain 1, active site 1, short sequence motif 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
8C2Z	X-RAY DIFFRACTION	1.91

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y463-F1	74.62	0.54

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 239 (proton acceptor)

Ligand- & substrate-binding residues (3): 117–125; 140; 190–193

Post-translational modifications (10): 63, 92, 111, 129, 171, 262, 271, 273, 401, 624

Mutagenesis-validated functional residues (4):

Position	Phenotype
140	abolishes kinase activity.
239	abolishes kinase activity.
271	abolishes kinase activity; when associated with f-273.
273	abolishes kinase activity; when associated with f-271.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 148 (showing top): GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, RACCACAR_AML_Q6, BIOCARTA_SHH_PATHWAY, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, YY1_02, AAAGACA_MIR511, GOBP_DNA_DAMAGE_RESPONSE, KUUSELO_PANCREATIC_CANCER_19Q13_AMPLIFICATION, GOBP_MYOTUBE_DIFFERENTIATION, GOBP_CONNECTIVE_TISSUE_DEVELOPMENT, XU_GH1_AUTOCRINE_TARGETS_DN, GOBP_ADIPOSE_TISSUE_DEVELOPMENT, GOBP_SYNCYTIUM_FORMATION, GOBP_MYOBLAST_FUSION, GCCATNTTG_YY1_Q6

GO Biological Process (7): DNA repair (GO:0006281), protein phosphorylation (GO:0006468), myoblast fusion (GO:0007520), positive regulation of DNA-templated transcription (GO:0045893), adipose tissue development (GO:0060612), DNA damage response (GO:0006974), protein autophosphorylation (GO:0046777)

GO Molecular Function (11): transcription coactivator activity (GO:0003713), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), protein serine/threonine/tyrosine kinase activity (GO:0004712), protein tyrosine kinase activity (GO:0004713), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694), nucleolus (GO:0005730)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
nuclear lumen	2
intracellular membraneless organelle	2
DNA metabolic process	1
DNA damage response	1
phosphorylation	1
protein modification process	1
syncytium formation by cell-cell fusion	1
myotube differentiation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
animal organ development	1
connective tissue development	1
cellular response to stress	1
protein phosphorylation	1
transcription coregulator activity	1
positive regulation of DNA-templated transcription	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYRK1B	DCAF7	P61962	863
DYRK1B	PCBD2	Q9H0N5	854
DYRK1B	PCBD1	P61457	706
DYRK1B	SLC13A5	Q86YT5	658
DYRK1B	HNF1A	P20823	649
DYRK1B	RNF169	Q8NCN4	590
DYRK1B	LIN52	Q52LA3	550
DYRK1B	RBL2	Q08999	537
DYRK1B	SLCO6A1	Q86UG4	521
DYRK1B	CTBP2	P56545	493
DYRK1B	FAM76A	Q8TAV0	489
DYRK1B	SMAD3	P84022	453
DYRK1B	TRADD	Q15628	450
DYRK1B	FOXK1	P85037	436
DYRK1B	STRADB	Q9C0K7	424

IntAct

65 interactions, top by confidence:

A	B	Type	Score
DCAF7	DYRK1B	psi-mi:“MI:0407”(direct interaction)	0.890
KIF24	CCP110	psi-mi:“MI:0914”(association)	0.810
TROAP	DYRK1B	psi-mi:“MI:0915”(physical association)	0.790
DYRK1B	TROAP	psi-mi:“MI:0915”(physical association)	0.790
HNF1A	PCBD2	psi-mi:“MI:0914”(association)	0.760
DYRK1B	LZTS2	psi-mi:“MI:0915”(physical association)	0.740
LZTS2	DYRK1B	psi-mi:“MI:0915”(physical association)	0.740
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.730
DYRK1B	HNF1A	psi-mi:“MI:0407”(direct interaction)	0.710
DYRK1B	HNF1A	psi-mi:“MI:0217”(phosphorylation reaction)	0.710
HNF1A	DYRK1B	psi-mi:“MI:0217”(phosphorylation reaction)	0.710
MAP3K1	DCAF7	psi-mi:“MI:0914”(association)	0.710
DYRK1B	RBL1	psi-mi:“MI:0915”(physical association)	0.670
DYRK1B	RB1	psi-mi:“MI:0915”(physical association)	0.670
RB1	DYRK1B	psi-mi:“MI:0915”(physical association)	0.670
DYRK1B	RANBP9	psi-mi:“MI:0915”(physical association)	0.630
RANBP9	DYRK1B	psi-mi:“MI:0407”(direct interaction)	0.630
DCAF7	PFDN6	psi-mi:“MI:0914”(association)	0.570
GSC2	DYRK1B	psi-mi:“MI:0915”(physical association)	0.560
PLK1	C1orf226	psi-mi:“MI:0914”(association)	0.560
HSP90AB1	DYRK1B	psi-mi:“MI:0915”(physical association)	0.560
DYRK1B	MAP2K3	psi-mi:“MI:0915”(physical association)	0.540
MAP2K3	DYRK1B	psi-mi:“MI:0217”(phosphorylation reaction)	0.540

BioGRID (158): DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), ID2 (Biochemical Activity), DYRK1B (Affinity Capture-Western), DYRK1B (Biochemical Activity), DYRK1B (Affinity Capture-Western), DCAF7 (Affinity Capture-Western), DYRK1B (Affinity Capture-Western), DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS), DYRK1B (Affinity Capture-MS)

ESM2 similar proteins: A5PKJ4, B1AK53, B8Y466, D3ZG83, O14976, O54967, O60307, O70405, O75385, O96013, P0C865, P80192, P97756, Q02779, Q13164, Q17R13, Q2YDU3, Q3U1V8, Q3U214, Q3U2S4, Q3ULB5, Q3V016, Q4KMP7, Q4V793, Q5I1X5, Q5R8Z4, Q5TCX8, Q5U2X5, Q66HA1, Q66L42, Q6NZR5, Q6ZRS2, Q80XI6, Q80Y86, Q8BHL3, Q8BTW9, Q8C078, Q8CIP4, Q8N5S9, Q8TD08

Diamond homologs: A4L9P5, A8WJR8, A8X4H1, A8X5H5, B3WFY8, G5EDB2, O14132, O23145, O43781, O55076, O76039, O88850, O88904, P14680, P18265, P18431, P20911, P22518, P24941, P43288, P43289, P48963, P49657, P49759, P49840, P50613, P51136, P51567, P51568, P51952, P83102, Q00526, Q03147, Q04859, Q07538, Q08DZ2, Q09690, Q09815, Q0IJ08, Q10156

SIGNOR signaling

18 interactions.

A	Effect	B	Mechanism
DYRK1B	down-regulates	CCND1	phosphorylation
RANBP9	“down-regulates activity”	DYRK1B	binding
DYRK1B	“down-regulates activity”	ID2	phosphorylation
DYRK1B	“down-regulates quantity by destabilization”	NKX3-1	phosphorylation
DYRK1B	up-regulates	DYRK1B	phosphorylation
DYRK1B	up-regulates	HNF1A	phosphorylation
MAP2K3	up-regulates	DYRK1B	phosphorylation
DYRK1B	“up-regulates activity”	CDKN1A	phosphorylation
DYRK1B	down-regulates	Apoptosis
DYRK1B	up-regulates	CDKN1B	phosphorylation
DYRK1B	“down-regulates activity”	HDAC5	phosphorylation
DYRK1B	down-regulates	HDAC9	phosphorylation
DYRK1B	up-regulates	MEF2C
DCAF7	“up-regulates activity”	DYRK1B	binding
DYRK1B	“down-regulates activity”	GYS1	phosphorylation
MAPK1	“up-regulates activity”	DYRK1B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 57 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
regulation of cell cycle	6	8.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

361 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	190
Likely benign	135
Benign	15

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
132792	NM_004714.3(DYRK1B):c.304C>T (p.Arg102Cys)	Pathogenic
132793	NM_004714.3(DYRK1B):c.269A>C (p.His90Pro)	Pathogenic

SpliceAI

1460 predictions. Top by Δscore:

Variant	Effect	Δscore
19:39826084:GACC:G	acceptor_loss	1.0000
19:39826085:ACC:A	acceptor_loss	1.0000
19:39826087:CTAA:C	acceptor_loss	1.0000
19:39826176:TTA:T	donor_loss	1.0000
19:39826178:ACCT:A	donor_loss	1.0000
19:39826199:CAGT:C	donor_gain	1.0000
19:39826282:GCCTC:G	acceptor_gain	1.0000
19:39826283:CCTCC:C	acceptor_gain	1.0000
19:39826284:CTC:C	acceptor_gain	1.0000
19:39826285:TC:T	acceptor_gain	1.0000
19:39826286:CC:C	acceptor_gain	1.0000
19:39826286:CCTGG:C	acceptor_loss	1.0000
19:39826287:C:CA	acceptor_loss	1.0000
19:39826287:C:CC	acceptor_gain	1.0000
19:39826293:G:C	acceptor_gain	1.0000
19:39826293:G:GC	acceptor_gain	1.0000
19:39826297:C:CT	acceptor_gain	1.0000
19:39826297:C:T	acceptor_gain	1.0000
19:39826298:A:T	acceptor_gain	1.0000
19:39827279:CCGCA:C	donor_loss	1.0000
19:39827280:CGCA:C	donor_loss	1.0000
19:39827281:GCAC:G	donor_loss	1.0000
19:39827282:CA:C	donor_loss	1.0000
19:39827283:ACCTT:A	donor_gain	1.0000
19:39827284:CCTTC:C	donor_gain	1.0000
19:39827287:T:TA	donor_gain	1.0000
19:39827302:T:TA	donor_gain	1.0000
19:39827348:G:A	donor_gain	1.0000
19:39827421:TCGAC:T	acceptor_gain	1.0000
19:39827422:CGAC:C	acceptor_gain	1.0000

AlphaMissense

4051 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:39826828:G:T	R419S	1.000
19:39826848:A:G	L412P	1.000
19:39826863:A:G	L407P	1.000
19:39826872:A:G	F404S	1.000
19:39827340:A:G	F347S	1.000
19:39827418:T:G	Q321P	1.000
19:39827520:C:A	G315V	1.000
19:39827520:C:T	G315D	1.000
19:39827521:C:G	G315R	1.000
19:39827525:G:C	F313L	1.000
19:39827525:G:T	F313L	1.000
19:39827526:A:G	F313S	1.000
19:39827527:A:G	F313L	1.000
19:39827527:A:T	F313I	1.000
19:39827529:A:T	L312H	1.000
19:39827538:C:A	G309V	1.000
19:39827538:C:T	G309E	1.000
19:39827539:C:G	G309R	1.000
19:39827539:C:T	G309R	1.000
19:39827549:C:A	E305D	1.000
19:39827549:C:G	E305D	1.000
19:39827550:T:A	E305V	1.000
19:39827551:C:T	E305K	1.000
19:39827556:A:G	L303P	1.000
19:39827556:A:T	L303H	1.000
19:39827561:G:C	C301W	1.000
19:39827562:C:T	C301Y	1.000
19:39827563:A:G	C301R	1.000
19:39827565:C:T	G300D	1.000
19:39827566:C:G	G300R	1.000

dbSNP variants (sampled 300 via entrez): RS1000419586 (19:39829288 G>A), RS1000603374 (19:39828928 G>A), RS1000681216 (19:39825103 C>A), RS1000920589 (19:39830851 G>A,C), RS1001128074 (19:39836068 T>A,C), RS1001658857 (19:39835224 A>T), RS1001799950 (19:39835539 AAAAT>A), RS1002021902 (19:39826042 C>T), RS1002353414 (19:39826076 G>A,C), RS1002536662 (19:39832628 A>G), RS1002756046 (19:39832906 T>C), RS1003176922 (19:39832934 T>A), RS1004441956 (19:39831240 T>C,G), RS1004495267 (19:39831596 G>A), RS1004710442 (19:39833293 C>A,T)

Disease associations

OMIM: gene MIM:604556 | disease phenotypes: MIM:615812

GenCC curated gene-disease

Disease	Classification	Inheritance
abdominal obesity-metabolic syndrome 3	Strong	Autosomal dominant

Mondo (2): abdominal obesity-metabolic syndrome 3 (MONDO:0014352), myoepithelial tumor (MONDO:0002380)

Orphanet (0):

HPO phenotypes

14 total (14 of 14 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000822	Hypertension
HP:0001297	Stroke
HP:0001658	Myocardial infarction
HP:0001956	Truncal obesity
HP:0002155	Hypertriglyceridemia
HP:0003074	Hyperglycemia
HP:0003124	Hypercholesterolemia
HP:0003141	Increased LDL cholesterol concentration
HP:0003596	Middle age onset
HP:0005145	Coronary artery stenosis
HP:0005978	Type II diabetes mellitus
HP:0011462	Young adult onset
HP:0012743	Abdominal obesity

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006976_36	Macular thickness	5.000000e-17

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009208	Myoepithelioma	C04.557.435.585

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL5543 (SINGLE PROTEIN), CHEMBL6195511 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195550 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

35 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 306,610 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1094636	NIRAPARIB	4	6,433
CHEMBL1173055	RUCAPARIB	4	7,009
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL140	CURCUMIN	3	93,882
CHEMBL2103839	RIDAFOROLIMUS	3	6,695
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL4297639	LORECIVIVINT	3	282
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1614713	CC-401	2	389
CHEMBL1721885	SU-014813	2
CHEMBL1967878	CENISERTIB	2
CHEMBL230011	TG100-115	2
CHEMBL384304	RG-547	2
CHEMBL445813	AT-7519	2
CHEMBL521851	PICTILISIB	2
CHEMBL607707	PELITINIB	2
CHEMBL1236107	SGX-523	1
CHEMBL1908397	KW-2449	1
CHEMBL1969664	AZD-1080	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Dyrk1 subfamily

Most potent curated ligand interactions (7 total), top 7:

Ligand	Action	Affinity	Parameter
compound 68 [PMID: 24900699]	Inhibition	9.62	pIC50
compound 72 [WO2013026806]	Inhibition	9.55	pIC50
compound 17 [PMID: 23642479]	Inhibition	8.15	pIC50
AZ191	Inhibition	7.77	pIC50
compound 3b [PMID: 23454515]	Inhibition	7.14	pIC50
voruciclib	Inhibition	7.03	pIC50
harmine	Inhibition	6.78	pIC50

Binding affinities (BindingDB)

127 measured of 128 human assays (128 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl 9-(2-bromo-4-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.16 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(2,4-dichloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.22 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(2-fluoro-4-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.36 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(2-methoxyethylcarbamoyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	0.699 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(pyrrolidine-1-carbonyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	0.852 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(2,4-difluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.94 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(4-methylanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.98 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(4-chloro-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	0.99 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(4-chloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	1.13 nM	US-9446044: DYRK1 inhibitors and uses thereof
N-(6-cyano-1H-benzimidazol-2-yl)-2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxamide	IC50	1.38 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(6-methylsulfonyl-1H-benzimidazol-2-yl)-1,3-thiazole-4-carboxamide	IC50	1.49 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(1,3-benzodioxol-5-ylamino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	1.65 nM	US-9446044: DYRK1 inhibitors and uses thereof
Staurosporine	KD	1.7 nM
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(dimethylcarbamoyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	1.74 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-anilino-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	1.81 nM	US-9446044: DYRK1 inhibitors and uses thereof
N-(6-chloro-1H-benzimidazol-2-yl)-2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxamide	IC50	1.9 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(5-pyridin-4-yl-1H-1,2,4-triazol-3-yl)-1,3-thiazole-4-carboxamide	IC50	2.06 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(4-ethylpiperazine-1-carbonyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	2.17 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-[(7-bromo-1,3-benzodioxol-5-yl)amino]-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	2.76 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(5-pyridin-3-yl-1H-1,2,4-triazol-3-yl)-1,3-thiazole-4-carboxamide	IC50	2.81 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-[4-(oxolan-2-ylmethyl)piperazine-1-carbonyl]-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	3.11 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
N-[5-(cyclopropylcarbamoyl)-1H-1,2,4-triazol-3-yl]-2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxamide	IC50	3.51 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	3.6 nM	US-9446044: DYRK1 inhibitors and uses thereof
ethyl 2-[[2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carbonyl]amino]-3H-benzimidazole-5-carboxylate	IC50	3.63 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(morpholine-4-carbonyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	3.72 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(4-cyanoanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	3.89 nM	US-9446044: DYRK1 inhibitors and uses thereof
N-[3-(cyanomethylsulfanyl)-1H-1,2,4-triazol-5-yl]-2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxamide	IC50	3.97 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(3H-benzimidazol-5-ylamino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	4.44 nM	US-9446044: DYRK1 inhibitors and uses thereof
US9446044, 60	IC50	4.91 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(2,4-dichloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboxylate	IC50	5.1 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(thiophene-2-carbonyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	5.57 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
ethyl 9-(1,3-benzodioxol-5-ylamino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	6.02 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(4-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	6.06 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(1H-pyrrole-2-carbonyl)-1H-benzimidazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	6.63 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
N-(1H-benzimidazol-2-yl)-2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carboxamide	IC50	6.73 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(3-propylsulfanyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-4-carboxamide	IC50	7.97 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(2,3-dihydro-1,4-benzodioxin-6-ylamino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	8 nM	US-9446044: DYRK1 inhibitors and uses thereof
US9446044, 79	IC50	8.63 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(morpholine-4-carbonyl)-1,3-benzothiazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	9.17 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(2,4-dimethoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	9.53 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[5-(methylcarbamoyl)-1H-1,2,4-triazol-3-yl]-1,3-thiazole-4-carboxamide	IC50	9.68 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(3-prop-2-enylsulfanyl-1H-1,2,4-triazol-5-yl)-1,3-thiazole-4-carboxamide	IC50	11.9 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(5-piperidin-1-yl-1,3,4-thiadiazol-2-yl)-1,3-thiazole-4-carboxamide	IC50	12.6 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
methyl 9-(4-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	13.1 nM	US-9446044: DYRK1 inhibitors and uses thereof
methyl 9-(3-chloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	IC50	13.6 nM	US-9446044: DYRK1 inhibitors and uses thereof
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(6-methoxy-1H-benzimidazol-2-yl)-1,3-thiazole-4-carboxamide	IC50	13.9 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
ethyl 1-[5-[[2-(2,3-dihydro-1-benzofuran-5-yl)-1,3-thiazole-4-carbonyl]amino]-1,3,4-thiadiazol-2-yl]piperidine-4-carboxylate	IC50	14.4 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[5-(furan-2-yl)-1H-1,2,4-triazol-3-yl]-1,3-thiazole-4-carboxamide	IC50	15.3 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-[6-(morpholin-4-ylmethyl)-1,3-benzothiazol-2-yl]-1,3-thiazole-4-carboxamide	IC50	15.7 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors
2-(2,3-dihydro-1-benzofuran-5-yl)-N-(1-methylbenzimidazol-2-yl)-1,3-thiazole-4-carboxamide	IC50	17.6 nM	US-10005769: 2,3-dihydrobenzofuran-5YL compounds as DYRK kinase inhibitors

ChEMBL bioactivities

1129 potent at pChembl≥5 of 1192 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.30	Kd	0.05	nM	CHEMBL5093650
9.62	IC50	0.24	nM	CHEMBL2386744
9.62	IC50	0.24	nM	CHEMBL2386770
9.55	IC50	0.28	nM	CHEMBL2386747
9.23	IC50	0.59	nM	CHEMBL2386745
9.23	IC50	0.59	nM	CHEMBL3894571
9.20	Ki	0.631	nM	CHEMBL1965660
9.02	IC50	0.967	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL3421963
9.00	IC50	1	nM	CHEMBL5091510
9.00	IC50	1	nM	CHEMBL5090676
9.00	IC50	1	nM	CHEMBL5092157
9.00	IC50	1	nM	CHEMBL5082044
9.00	IC50	1	nM	CHEMBL5083159
9.00	IC50	1	nM	CHEMBL5091238
9.00	IC50	1	nM	CHEMBL5400230
9.00	IC50	1	nM	CHEMBL5405059
9.00	IC50	1	nM	CHEMBL5422486
9.00	Ki	1	nM	CHEMBL1980407
8.99	IC50	1.02	nM	CHEMBL5574295
8.97	IC50	1.07	nM	CHEMBL2386748
8.96	IC50	1.1	nM	CHEMBL4441878
8.96	IC50	1.1	nM	CHEMBL5070553
8.94	IC50	1.14	nM	STAUROSPORINE
8.92	IC50	1.21	nM	STAUROSPORINE
8.82	IC50	1.52	nM	STAUROSPORINE
8.79	IC50	1.63	nM	CHEMBL2386746
8.79	IC50	1.63	nM	CHEMBL3971170
8.74	IC50	1.8	nM	CHEMBL5091238
8.70	IC50	2	nM	CHEMBL3421962
8.70	IC50	2	nM	CHEMBL4872233
8.70	IC50	2	nM	CIRTUVIVINT
8.70	IC50	2	nM	CHEMBL5417147
8.70	IC50	2	nM	CHEMBL5409574
8.70	IC50	2	nM	CHEMBL5429404
8.70	Ki	1.995	nM	CHEMBL1981133
8.70	Ki	1.995	nM	CHEMBL2007574
8.62	Kd	2.4	nM	CHEMBL6171139
8.60	Ki	2.512	nM	CHEMBL1986943
8.57	IC50	2.7	nM	CHEMBL5070553
8.55	IC50	2.83	nM	CHEMBL2386764
8.52	IC50	3	nM	CHEMBL3421968
8.52	IC50	3	nM	CHEMBL3421981
8.52	IC50	3	nM	STAUROSPORINE
8.52	IC50	3	nM	CHEMBL4873449
8.52	IC50	3	nM	CHEMBL5093650
8.47	IC50	3.4	nM	CHEMBL393525
8.47	Kd	3.4	nM	CHEMBL6165903
8.46	IC50	3.48	nM	CHEMBL2386763
8.46	IC50	3.5	nM	ABEMACICLIB

PubChem BioAssay actives

870 with measured affinity, of 1945 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-(2-amino-4-pyridinyl)-N-[(2,6-difluorophenyl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812183: Inhibition of human wild type DYRK1B (M1 to S629) expressed in bacterial system by DiscoveryX Kinomescan binding assay	kd	0.0001	uM
methyl 9-(4-bromo-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748669: Inhibition of recombinant DYRK1B (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0002	uM
methyl 9-(2,4-dichloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714122: Inhibition of human DYRK1B using [33P]-ATP incubated for 120 mins	ic50	0.0003	uM
methyl 9-(2-fluoro-4-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714122: Inhibition of human DYRK1B using [33P]-ATP incubated for 120 mins	ic50	0.0006	uM
methyl 9-(4-fluoro-2-methoxyanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748669: Inhibition of recombinant DYRK1B (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0006	uM
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-4-amine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0010	uM
5-(2-amino-4-pyridinyl)-N-benzyl-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812155: Inhibition of DYRK1B (unknown origin) by TR FRET assay	ic50	0.0010	uM
4-[2-methyl-4-(thiophen-3-ylmethoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-2-amine	1812155: Inhibition of DYRK1B (unknown origin) by TR FRET assay	ic50	0.0010	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-hydroxy-1-adamantyl)imino]imidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3,5,7-trifluoro-1-adamantyl)imino]imidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	uM
5-(2-amino-4-pyridinyl)-2-methyl-N-(thiophen-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812155: Inhibition of DYRK1B (unknown origin) by TR FRET assay	ic50	0.0010	uM
5-(2-amino-4-pyridinyl)-2-methyl-N-(thiophen-3-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812155: Inhibition of DYRK1B (unknown origin) by TR FRET assay	ic50	0.0010	uM
4-[2-methyl-4-(1,3-thiazol-5-ylmethoxy)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]pyridin-2-amine	1812155: Inhibition of DYRK1B (unknown origin) by TR FRET assay	ic50	0.0010	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3-tricyclo[3.3.1.03,7]nonanylimino)imidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	uM
(2S)-2-[[6-(6-methyl-1H-pyrrolo[2,3-b]pyridin-3-yl)quinazolin-4-yl]amino]-2-phenylethanol	2110571: Inhibition of DYRK1B (unknown origin) preincubated with enzyme for 10 mins followed by substrate and ATP addition measured after 60 mins by ADP-Glo reagent based assay	ic50	0.0010	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531666: Inhibition of human DYRK1B using RRRFRPASPLRGPPK as substrate by [gamma-33P]-ATP assay	ic50	0.0010	uM
4-[2-methyl-3-(2,2,2-trifluoroethyl)imidazo[4,5-b]pyridin-5-yl]pyridine-2,6-diamine	1947693: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay	ic50	0.0011	uM
4-(2-methyl-3-propan-2-ylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1947693: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay	ic50	0.0011	uM
methyl 9-(2,4-difluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714122: Inhibition of human DYRK1B using [33P]-ATP incubated for 120 mins	ic50	0.0011	uM
methyl 9-(4-chloro-2-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714122: Inhibition of human DYRK1B using [33P]-ATP incubated for 120 mins	ic50	0.0016	uM
methyl 9-(2-chloro-4-fluoroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748669: Inhibition of recombinant DYRK1B (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0016	uM
N-[4-(4-methylpiperazin-1-yl)phenyl]-6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-4-amine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0020	uM
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1851276: Inhibition of DYRK1B (unknown origin)	ic50	0.0020	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-methoxy-1-adamantyl)imino]imidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]imino]imidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
[4-[3-(4-methoxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]phenyl]urea	1764190: Inhibition of DYRK1B (unknown origin)	ic50	0.0020	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]methanesulfonamide	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
methyl 9-(4-methylanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	1714122: Inhibition of human DYRK1B using [33P]-ATP incubated for 120 mins	ic50	0.0028	uM
3-(1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrrolo[2,3-c]pyridine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0030	uM
4-[3-(4-hydroxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]benzene-1,2-diol	1764190: Inhibition of DYRK1B (unknown origin)	ic50	0.0030	uM
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-4-(1-methylpyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0030	uM
N-[(E)-(6-bromoimidazo[1,2-a]pyridin-3-yl)methylideneamino]-N,2-dimethyl-5-nitrobenzenesulfonamide	1947693: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay	ic50	0.0034	uM
Abemaciclib	1947683: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0035	uM
methyl 9-anilino-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748669: Inhibition of recombinant DYRK1B (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0035	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624964: Binding constant for DYRK1B kinase domain	kd	0.0039	uM
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-4-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0040	uM
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-4-(5-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0040	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]acetamide	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
2-(1-adamantylamino)-5-[(E)-benzimidazol-5-ylidenemethyl]-1H-imidazol-4-ol	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
methyl 9-(1,3-benzodioxol-5-ylamino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748669: Inhibition of recombinant DYRK1B (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0042	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1947693: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay	ic50	0.0046	uM
methyl 9-(4-chloroanilino)-[1,3]thiazolo[5,4-f]quinazoline-2-carboximidate	748669: Inhibition of recombinant DYRK1B (unknown origin) after 120 mins in presence of [33P]-ATP	ic50	0.0047	uM
N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]-1-methylsulfonylpiperidine-4-carboxamide	1947693: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells using DYRKtide peptide as substrate incubated for 110 mins in presence of ATP by non-radioactive ADP-Glo luminescence microplate reader assay	ic50	0.0048	uM
N-[2-methoxy-4-(4-methylpiperazin-1-yl)phenyl]-4-(7-methyl-1H-pyrrolo[2,3-c]pyridin-3-yl)pyrimidin-2-amine	1203152: Inhibition of recombinant Dyrk1B (unknown origin) using FITC-Asp-His-Thr-Gly-Phe-Leu-Thr-Glu-Tyr-Val-Ala-Thr-Arg-NH2 as substrate after 60 mins	ic50	0.0050	uM
(3R)-1-[3-[[3-amino-6-(2-fluoro-5-propan-2-yloxyphenyl)pyrazine-2-carbonyl]amino]-4-pyridinyl]piperidine-3-carboxylic acid	1947683: Inhibition of recombinant human DYRK1B expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0050	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R)-2-hydroxy-1-phenylethyl]iminoimidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0050	uM
N-[4-[3-(4-hydroxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]phenyl]methanesulfonamide	1764190: Inhibition of DYRK1B (unknown origin)	ic50	0.0050	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocycloheptyl)iminoimidazolidin-4-one	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0050	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]cyclopropanecarboxamide	2010391: Inhibition of human DYRK1B using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0050	uM

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	decreases expression, increases abundance, increases expression	3
Air Pollutants	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
multi-kinase inhibitor 108600	decreases activity, decreases phosphorylation	1
triphenyl phosphate	affects expression	1
terbufos	increases methylation	1
beta-lapachone	decreases expression	1
sodium arsenite	increases expression	1
5-iodotubercidin	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
(+)-JQ1 compound	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	affects response to substance	1
Arsenic Trioxide	increases expression	1
Arsenic	affects methylation	1
Vehicle Emissions	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Carmustine	affects response to substance	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Fonofos	increases methylation	1
Estradiol	decreases expression	1
Ivermectin	decreases expression	1
Niclosamide	increases expression	1
Parathion	increases methylation	1
Silicon Dioxide	decreases expression	1
Smoke	decreases expression	1
Testosterone	decreases expression	1
Dronabinol	increases expression	1
Valproic Acid	increases methylation	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

422 unique, capped per target: 412 binding, 5 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1034106	Binding	Inhibition of DYRK1B at 3 uM	Discovery of substituted 4-(pyrazol-4-yl)-phenylbenzodioxane-2-carboxamides as potent and highly selective Rho kinase (ROCK-II) inhibitors. — J Med Chem
CHEMBL1738101	Functional	PUBCHEM_BIOASSAY: Kinase Inhibition Study on Inhibitors of Dyrk1b (Reaction Biology data). (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1459, AID1487, AID1498, AID1770, AID1970, AID1997, AID488872, AID488883	PubChem BioAssay data set
CHEMBL4263630	ADMET	Inhibition of recombinant full length human Dyrk1B expressed in Baculovirus expression system at 250 nM using KKISGRLSPIMTEQ as substrate in presence of ATP	Development of novel 2,4-bispyridyl thiophene-based compounds as highly potent and selective Dyrk1A inhibitors. Part I: Benzamide and benzylamide derivatives. — Eur J Med Chem

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SL23	HAP1 DYRK1B (-)	Cancer cell line	Male

Clinical trials (associated diseases)

5 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT03600649	PHASE1	UNKNOWN	Clinical Trial of SP-2577 (Seclidemstat) in Patients With Relapsed or Refractory Ewing or Ewing-related Sarcomas
NCT05266196	PHASE1/PHASE2	UNKNOWN	A Rollover Protocol to Allow for Continued Access to the LSD1 Inhibitor Seclidemstat (SP-2577)
NCT06239272	PHASE1/PHASE2	RECRUITING	NRSTS2021, A Risk Adapted Study Evaluating Maintenance Pazopanib, Limited Margin, Dose-Escalated Radiation Therapy and Selinexor in Non-Rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS)
NCT06625190	PHASE1/PHASE2	RECRUITING	Alpha/Beta T and B Cell Depletion With Zoledronic Acid for Solid Tumors
NCT06244420	Not specified	COMPLETED	Malignant Myoepithelioma of Bone and Soft Tissues: Diagnostic Imaging and Histology in Relation to Prognosis