DYRK4

Summary

DYRK4 (dual specificity tyrosine phosphorylation regulated kinase 4, HGNC:3095) is a protein-coding gene on chromosome 12p13.32, encoding Dual specificity tyrosine-phosphorylation-regulated kinase 4 (Q9NR20). Possible non-essential role in spermiogenesis.

This gene encodes an enzyme that belongs to a conserved family of serine/threonine protein kinases. Members of this dual specificity kinase family are thought to function in the regulation of cell differentiation and proliferation, survival, and in development. Alternate splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known.

Source: NCBI Gene 8798 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 92 total
• Druggable target: yes — 7 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001394779

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3095
Approved symbol	DYRK4
Name	dual specificity tyrosine phosphorylation regulated kinase 4
Location	12p13.32
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000010219
Ensembl biotype	protein_coding
OMIM	609181
Entrez	8798

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 8 retained_intron, 4 protein_coding, 3 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000010132, ENST00000536137, ENST00000536157, ENST00000536645, ENST00000537719, ENST00000538520, ENST00000539309, ENST00000539490, ENST00000539701, ENST00000540644, ENST00000540757, ENST00000541024, ENST00000542905, ENST00000543431, ENST00000544050, ENST00000544671, ENST00000545571

RefSeq mRNA: 7 — MANE Select: NM_001394779 NM_001282285, NM_001282286, NM_001371301, NM_001394779, NM_001394780, NM_001407019, NM_003845

CCDS: CCDS8530, CCDS91641

Canonical transcript exons

ENST00000543431 — 15 exons

Exon	Start	End
ENSE00000893103	4596149	4596285
ENSE00000893104	4596589	4596729
ENSE00000893105	4599028	4599166
ENSE00000893106	4599707	4599788
ENSE00002266354	4613515	4613875
ENSE00002322043	4562208	4562283
ENSE00003523302	4590330	4590440
ENSE00003536783	4607327	4607387
ENSE00003542762	4610155	4610284
ENSE00003562060	4593002	4593165
ENSE00003586091	4612543	4612718
ENSE00003630973	4588937	4589017
ENSE00003653654	4604914	4605086
ENSE00003654399	4591160	4591298
ENSE00003682578	4567955	4568048

Expression profiles

Bgee: expression breadth ubiquitous, 245 present calls, max score 98.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.9939 / max 176.0420, expressed in 1804 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
123576	29.7691	1801
123577	0.7113	424
123572	0.2530	72
123571	0.1396	37
123573	0.0948	45
123575	0.0178	4
206546	0.0083	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	98.38	gold quality
right testis	UBERON:0004534	98.26	gold quality
testis	UBERON:0000473	96.73	gold quality
adenohypophysis	UBERON:0002196	96.21	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	95.07	gold quality
pituitary gland	UBERON:0000007	94.72	gold quality
body of pancreas	UBERON:0001150	94.53	gold quality
body of uterus	UBERON:0009853	94.20	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.16	gold quality
left ovary	UBERON:0002119	94.04	gold quality
right ovary	UBERON:0002118	93.83	gold quality
right lobe of thyroid gland	UBERON:0001119	93.82	gold quality
thoracic aorta	UBERON:0001515	93.82	gold quality
ascending aorta	UBERON:0001496	93.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	93.73	gold quality
lower esophagus	UBERON:0013473	93.69	gold quality
lower esophagus muscularis layer	UBERON:0035833	93.69	gold quality
left uterine tube	UBERON:0001303	93.66	gold quality
rectum	UBERON:0001052	93.63	gold quality
left lobe of thyroid gland	UBERON:0001120	93.53	gold quality
descending thoracic aorta	UBERON:0002345	93.53	gold quality
right coronary artery	UBERON:0001625	93.25	gold quality
spinal cord	UBERON:0002240	93.22	gold quality
stromal cell of endometrium	CL:0002255	93.20	gold quality
endocervix	UBERON:0000458	93.15	gold quality
aorta	UBERON:0000947	92.90	gold quality
left adrenal gland	UBERON:0001234	92.79	gold quality
left coronary artery	UBERON:0001626	92.66	gold quality
thyroid gland	UBERON:0002046	92.65	gold quality
right adrenal gland	UBERON:0001233	92.62	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.99
E-MTAB-6142	no	36.75

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting DYRK4, 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-3924	100.00	72.09	2394
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-302E	99.96	70.74	2669
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-2053	99.57	69.15	1635
HSA-MIR-5590-3P	99.48	70.91	2429
HSA-MIR-622	98.99	66.48	1050
HSA-MIR-6876-3P	98.97	65.69	765

Literature-anchored findings (GeneRIF, showing 3)

• Dyrk4 is a testis-specific kinase with a very restricted expression to stage VIII postmeiotic spermatids. (PMID:17292540)
• DYRK4 isoforms resulting from alternative splicing differ in subcellular localization and catalytic activity (PMID:21127067)
• A Novel Neoplastic Fusion Transcript, RAD51AP1-DYRK4, Confers Sensitivity to the MEK Inhibitor Trametinib in Aggressive Breast Cancers. (PMID:33172895)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	dyrk4	ENSDARG00000070734
mus_musculus	Dyrk4	ENSMUSG00000030345
rattus_norvegicus	Dyrk4	ENSRNOG00000053178
drosophila_melanogaster	Dyrk2	FBGN0016930
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), 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 4 — Q9NR20 (reviewed: Q9NR20)

All UniProt accessions (6): Q9NR20, A0A0A0MTH5, F5GWS4, F5H3D3, F5H4X6, H0YFI4

UniProt curated annotations — full annotation on UniProt →

Function. Possible non-essential role in spermiogenesis.

Subcellular location. Cytoplasm Cytoplasm. Nucleus.

Post-translational modifications. Autophosphorylation on Tyr-264 in the activation loop is required for kinase activity.

Miscellaneous. May be due to a competing acceptor splice site. Due to an alternative splicing donor site in exon 19. Markedly reduced enzymatic activity.

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

Isoforms (5)

UniProt ID	Names	Canonical?
Q9NR20-1	1	yes
Q9NR20-2	2
Q9NR20-3	3
Q9NR20-4	4, DYRK4-L
Q9NR20-5	5

RefSeq proteins (5): NP_001358230, NP_001381708, NP_001381709, NP_001393948, NP_003836 (=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
IPR042521	DYRK	Homologous_superfamily
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 (24 total): sequence variant 5, splice variant 4, binding site 3, region of interest 2, mutagenesis site 2, compositionally biased region 2, chain 1, domain 1, modified residue 1, sequence conflict 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NR20-F1	78.50	0.65

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): 230 (proton acceptor)

Ligand- & substrate-binding residues (3): 110–118; 133; 183–186

Post-translational modifications (1): 264

Mutagenesis-validated functional residues (2):

Position	Phenotype
133	loss of kinase activity.
264	abolishes kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 94 (showing top): LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, BROWNE_HCMV_INFECTION_48HR_DN, BROWNE_HCMV_INFECTION_14HR_DN, CERVERA_SDHB_TARGETS_1_UP, IVANOVA_HEMATOPOIESIS_STEM_CELL_LONG_TERM, SENESE_HDAC3_TARGETS_DN, PARENT_MTOR_SIGNALING_UP, SMITH_TERT_TARGETS_UP, GOMF_PROTEIN_KINASE_ACTIVITY, GOMF_KINASE_ACTIVITY, GOMF_PROTEIN_SERINE_THREONINE_KINASE_ACTIVITY, GOMF_ADENYL_NUCLEOTIDE_BINDING, GOMF_TRANSFERASE_ACTIVITY_TRANSFERRING_PHOSPHORUS_CONTAINING_GROUPS, KYNG_WERNER_SYNDROM_AND_NORMAL_AGING_DN, CYCLIN_D1_KE_.V1_UP

GO Biological Process (1): protein phosphorylation (GO:0006468)

GO Molecular Function (11): 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), metal ion binding (GO:0046872), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): nucleus (GO:0005634), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
cation binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular anatomical structure	1
cellular anatomical structure	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

762 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
DYRK4	DCAF7	P61962	699
DYRK4	SLC13A5	Q86YT5	586
DYRK4	NRIP2	Q9BQI9	435
DYRK4	TRAPPC2L	Q9UL33	390
DYRK4	AAR2	Q9Y312	372
DYRK4	NFKBIL1	Q9UBC1	363
DYRK4	CHCHD3	Q9NX63	361
DYRK4	RNH1	P13489	348
DYRK4	RIPK2	O43353	333
DYRK4	CFAP77	Q6ZQR2	315
DYRK4	DLEU7	Q6UYE1	314
DYRK4	RNF169	Q8NCN4	313
DYRK4	ABHD14B	Q96IU4	313
DYRK4	SSMEM1	Q8WWF3	311
DYRK4	ZNF776	Q68DI1	308

IntAct

18 interactions, top by confidence:

A	B	Type	Score
DYRK2	DYRK4	psi-mi:“MI:0915”(physical association)	0.570
DYRK4	DYRK2	psi-mi:“MI:0915”(physical association)	0.570
MID1	DYRK4	psi-mi:“MI:0915”(physical association)	0.560
DYRK4	MID1	psi-mi:“MI:0915”(physical association)	0.560
HSP90AB1	DYRK4	psi-mi:“MI:0915”(physical association)	0.560
DYRK4	HSP90AA1	psi-mi:“MI:0915”(physical association)	0.560
DYRK4	CALML5	psi-mi:“MI:0915”(physical association)	0.400
YWHAE	DYRK4	psi-mi:“MI:0915”(physical association)	0.400
SFN	DYRK4	psi-mi:“MI:0915”(physical association)	0.400
DYRK4	CUL3	psi-mi:“MI:0915”(physical association)	0.370
PPP1CC	DYRK4	psi-mi:“MI:0915”(physical association)	0.370
DYRK4	HAX1	psi-mi:“MI:0914”(association)	0.350
FTL		psi-mi:“MI:0914”(association)	0.350
DYRK2	RB1CC1	psi-mi:“MI:0914”(association)	0.350
DYRK4	CDIPT	psi-mi:“MI:0914”(association)	0.350

BioGRID (38): DYRK4 (Two-hybrid), CALML5 (Affinity Capture-MS), HAX1 (Affinity Capture-MS), AIP (Affinity Capture-MS), DNAJB6 (Affinity Capture-MS), HSP90AA1 (Affinity Capture-MS), HSP90AB1 (Affinity Capture-MS), CNP (Affinity Capture-MS), DNAJB1 (Affinity Capture-MS), STIP1 (Affinity Capture-MS), DDOST (Affinity Capture-MS), ST13 (Affinity Capture-MS), PPP5C (Affinity Capture-MS), FKBP4 (Affinity Capture-MS), FKBP5 (Affinity Capture-MS)

ESM2 similar proteins: A0AUV4, A1A5Q6, A1A5R7, A2KF29, B1WAS2, C0HKC8, C0HKC9, O60285, O74536, O88831, O88866, P35125, P51956, P57058, Q20443, Q28283, Q2T9U5, Q4R9F7, Q5GLH2, Q5R669, Q5R7G9, Q5XHI9, Q66HE5, Q68UT7, Q6P431, Q6VZ17, Q7TNJ7, Q7TNL4, Q8BHI9, Q8BZN4, Q8C078, Q8C0N0, Q8C0V7, Q8C0X8, Q8K4K4, Q8NE63, Q8WP28, Q91VB2, Q92519, Q96L34

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

1 interactions.

A	Effect	B	Mechanism
DYRK4	“up-regulates activity”	DYRK4	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	67
Likely benign	5
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

2217 predictions. Top by Δscore:

Variant	Effect	Δscore
12:4593143:A:G	donor_gain	1.0000
12:4596274:G:GT	donor_gain	1.0000
12:4596275:A:T	donor_gain	1.0000
12:4596283:G:GT	donor_gain	1.0000
12:4596567:C:A	acceptor_gain	1.0000
12:4596680:G:GT	donor_gain	1.0000
12:4599026:A:AG	acceptor_gain	1.0000
12:4599027:G:GG	acceptor_gain	1.0000
12:4599027:GA:G	acceptor_gain	1.0000
12:4599163:GCCC:G	donor_gain	1.0000
12:4604912:A:AG	acceptor_gain	1.0000
12:4604913:G:GG	acceptor_gain	1.0000
12:4604913:GT:G	acceptor_gain	1.0000
12:4604913:GTAT:G	acceptor_gain	1.0000
12:4605084:G:GT	donor_gain	1.0000
12:4605085:AGG:A	donor_loss	1.0000
12:4605087:G:T	donor_loss	1.0000
12:4605088:T:A	donor_loss	1.0000
12:4610283:GT:G	donor_gain	1.0000
12:4613510:A:AG	acceptor_gain	1.0000
12:4613511:G:GG	acceptor_gain	1.0000
12:4613511:GC:G	acceptor_gain	1.0000
12:4613511:GCA:G	acceptor_gain	1.0000
12:4590436:ATCAG:A	donor_loss	0.9900
12:4590437:TCAG:T	donor_loss	0.9900
12:4590439:AGG:A	donor_loss	0.9900
12:4590440:GGTG:G	donor_loss	0.9900
12:4590441:G:A	donor_loss	0.9900
12:4590442:TGAG:T	donor_loss	0.9900
12:4591153:T:A	acceptor_gain	0.9900

AlphaMissense

4217 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:4596174:G:C	R103P	0.999
12:4604994:T:A	W288R	0.998
12:4604994:T:C	W288R	0.998
12:4612592:T:A	W399R	0.998
12:4612592:T:C	W399R	0.998
12:4596229:C:G	C121W	0.997
12:4596258:C:A	A131D	0.997
12:4596265:A:C	K133N	0.997
12:4596265:A:T	K133N	0.997
12:4596695:C:A	R176S	0.997
12:4596696:G:C	R176P	0.997
12:4599156:A:C	D230A	0.997
12:4599156:A:T	D230V	0.997
12:4599712:T:A	N235K	0.997
12:4599712:T:G	N235K	0.997
12:4599757:C:A	D250E	0.997
12:4599757:C:G	D250E	0.997
12:4612559:C:A	R388S	0.997
12:4596227:T:C	C121R	0.996
12:4596261:T:C	L132P	0.996
12:4599714:T:A	I236K	0.996
12:4599756:A:T	D250V	0.996
12:4604944:G:C	R271P	0.996
12:4604997:A:C	S289R	0.996
12:4604999:C:A	S289R	0.996
12:4604999:C:G	S289R	0.996
12:4596264:A:T	K133I	0.995
12:4596692:T:C	F175L	0.995
12:4596694:T:A	F175L	0.995
12:4596694:T:G	F175L	0.995

dbSNP variants (sampled 300 via entrez): RS1000015514 (12:4614372 A>G), RS1000082306 (12:4564589 G>A), RS1000085085 (12:4569963 G>C,T), RS1000129014 (12:4610735 G>C), RS1000220202 (12:4586180 C>A), RS1000346524 (12:4563258 C>A,T), RS1000535195 (12:4609305 C>T), RS1000550455 (12:4603340 A>G), RS1000580186 (12:4603676 A>G), RS1000609368 (12:4593946 T>G), RS1000644794 (12:4560408 C>A), RS1000703489 (12:4598757 A>C), RS1000733622 (12:4600316 T>C), RS1000775096 (12:4594073 A>C,G), RS1000776017 (12:4582601 T>C)

Disease associations

OMIM: gene MIM:609181 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST002550_18	Allergic rhinitis	2.000000e-07

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1075115 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 35,588 (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
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL475251	R-406	2	762
CHEMBL269538	HARMINE	1	4,346
CHEMBL4784318	CIRTUVIVINT	1	34
CHEMBL5426285	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-	1	4

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 (1 total), top 1:

Ligand	Action	Affinity	Parameter
leucettine L41	Inhibition	6.28	pIC50

ChEMBL bioactivities

330 potent at pChembl≥5 of 333 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CIRTUVIVINT
8.00	Ki	10	nM	CHEMBL1965660
7.90	Ki	12.59	nM	CHEMBL1981079
7.57	IC50	26.8	nM	CHEMBL4873449
7.48	IC50	33	nM	CHEMBL5400230
7.40	IC50	40	nM	CHEMBL3103192
7.40	Ki	39.81	nM	CHEMBL1978448
7.33	IC50	47	nM	CHEMBL5438158
7.32	IC50	48	nM	CHEMBL5405059
7.30	Ki	50.12	nM	CHEMBL1964290
7.10	IC50	80	nM	CHEMBL5420645
7.09	IC50	82	nM	CHEMBL5408907
7.06	IC50	86.4	nM	CIRTUVIVINT
6.97	IC50	108	nM	CHEMBL5081787
6.97	IC50	108	nM	CHEMBL5438293
6.93	IC50	117.4	nM	CHEMBL5091238
6.93	IC50	117	nM	CHEMBL5091238
6.92	IC50	121	nM	CHEMBL5440139
6.90	IC50	127	nM	CHEMBL5417207
6.90	IC50	127	nM	CHEMBL5421442
6.90	Ki	125.9	nM	CHEMBL1998159
6.90	Ki	125.9	nM	CHEMBL539474
6.86	IC50	137	nM	CHEMBL5414514
6.86	IC50	137	nM	CHEMBL5441121
6.84	IC50	143	nM	CHEMBL5396991
6.84	IC50	146	nM	CHEMBL5427842
6.84	IC50	146	nM	CHEMBL5422486
6.81	IC50	155	nM	CHEMBL5414635
6.80	Ki	158.5	nM	CHEMBL1995813
6.77	IC50	170.6	nM	CHEMBL4441878
6.76	IC50	174	nM	CHEMBL5396550
6.76	IC50	174	nM	CHEMBL5406081
6.75	IC50	180	nM	CHEMBL5398161
6.74	IC50	181	nM	CHEMBL5428132
6.70	Ki	199.5	nM	CHEMBL225519
6.66	IC50	218	nM	CHEMBL5404416
6.66	IC50	221	nM	CHEMBL5412900
6.64	IC50	227	nM	CHEMBL5428629
6.63	IC50	233	nM	CHEMBL5409574
6.61	IC50	248	nM	5-(6-BENZOTHIAZOLYLMETHYLENE)-3,5-DIHYDRO-2-(((1S)-1-(METHOXYMETHYL)-3-METHYLBUTYL)AMINO)-4H-IMIDAZOL-4-ONE, (5Z)-
6.61	IC50	244	nM	CHEMBL5397343
6.61	IC50	246	nM	CHEMBL5405233
6.60	Ki	251.2	nM	CHEMBL1982957
6.60	Ki	251.2	nM	CHEMBL1970903
6.59	IC50	257	nM	CHEMBL5418020
6.58	IC50	260	nM	CHEMBL5412998
6.58	IC50	263	nM	CHEMBL5422654
6.57	IC50	270	nM	CHEMBL5418722
6.56	IC50	274	nM	CHEMBL5439276
6.55	IC50	284	nM	CHEMBL5417147

PubChem BioAssay actives

236 with measured affinity, of 953 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
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1851278: Inhibition of DYRK4 (unknown origin)	ic50	0.0020	uM
4-[3-(4-hydroxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]benzene-1,2-diol	1947686: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0268	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3-tricyclo[3.3.1.03,7]nonanylimino)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0330	uM
N-[2-[2-aminoethyl(methyl)amino]-5-[[3-cyano-7-(cyclopropylamino)pyrazolo[1,5-a]pyrimidin-5-yl]amino]phenyl]acetamide	1301623: Inhibition of Dyrk4 (unknown origin) by quantitative PCR	ic50	0.0400	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-fluoro-1-adamantyl)imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0470	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-hydroxy-1-adamantyl)imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0480	uM
(5Z)-2-(1-adamantylimino)-5-[(3-methylbenzimidazol-5-yl)methylidene]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0800	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-methoxycyclopentyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0820	uM
(5Z)-2-(2,6-dichlorophenyl)imino-5-(quinoxalin-6-ylmethylidene)-1,3-thiazolidin-4-one	1947686: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.1080	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzoxazol-6-ylmethylidene)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1080	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1170	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,3R)-3-methoxycyclohexyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1210	uM
(5Z)-2-(2-adamantylimino)-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1270	uM
[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl] N-tert-butylcarbamate	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1270	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2S)-2-hydroxycycloheptyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1370	uM
(5Z)-2-[(1S)-2-amino-1-phenylethyl]imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1370	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2,2-difluorocyclohexyl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1430	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1S,2S)-2-methoxycyclopentyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1460	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3,5,7-trifluoro-1-adamantyl)imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1460	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(1R,2R)-2-methoxy-2,3-dihydro-1H-inden-1-yl]imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1550	uM
4-(2-methyl-3-propan-2-ylimidazo[4,5-b]pyridin-5-yl)pyridine-2,6-diamine	1947686: Inhibition of recombinant human DYRK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.1706	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocycloheptyl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1740	uM
(5Z)-2-[(1R)-2-amino-1-phenylethyl]imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1740	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(1R,2R)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1800	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2S)-2-hydroxy-2-phenylethyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.1810	uM
2-(1-adamantylamino)-5-[(E)-benzimidazol-5-ylidenemethyl]-1H-imidazol-4-ol	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2180	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(2R)-1,7,7-trimethyl-2-bicyclo[2.2.1]heptanyl]imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2210	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-methoxycycloheptyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2270	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]methanesulfonamide	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2330	uM
(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-2-[4-(4-methylpiperazin-1-yl)anilino]-1H-imidazol-5-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2440	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(thian-3-ylimino)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2460	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-methoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2480	uM
(4Z)-2-anilino-4-(1,3-benzothiazol-6-ylmethylidene)-1H-imidazol-5-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2570	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2-bicyclo[2.2.1]heptanylimino)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2600	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]acetamide	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2630	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]cyclopropanecarboxamide	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2700	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[2-(methylamino)-1-phenylethyl]iminoimidazolidin-4-one;dihydrochloride	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2740	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3-methoxy-1-adamantyl)imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2840	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2-hydroxy-3-phenylpropyl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2880	uM
(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-2-[[2-(4-methylpiperazin-1-yl)pyrimidin-5-yl]amino]-1H-imidazol-5-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.2940	uM
(5Z)-2-(2-amino-1-phenylethyl)imino-5-(1,3-benzothiazol-6-ylmethylidene)imidazolidin-4-one;dihydrochloride	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3170	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2-cyclohexyl-2-hydroxyethyl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3190	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(5-hydroxy-2-adamantyl)imino]imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3210	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocyclohexyl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3210	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocyclopentyl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3260	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R)-2-methoxy-1-phenylethyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3350	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2R)-2-hydroxycycloheptyl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3570	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(1-methoxy-3-phenylpropan-2-yl)iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3740	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(oxepan-3-ylimino)imidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3830	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2S)-1-fluoro-4-methylpentan-2-yl]iminoimidazolidin-4-one	2010394: Inhibition of human DYRK4 using RBERCHKtide and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.3850	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cyclosporine	increases expression	3
Tunicamycin	increases expression	2
triphenyl phosphate	affects expression	1
beta-lapachone	increases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
cobaltous chloride	decreases expression	1
tanshinone	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
5-iodotubercidin	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
bisphenol S	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
Vorinostat	increases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects expression	1
Indomethacin	affects cotreatment, increases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methyl Methanesulfonate	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Aflatoxin B1	decreases expression	1
Thapsigargin	increases expression	1
Particulate Matter	increases expression, increases abundance	1

ChEMBL screening assays

94 unique, capped per target: 93 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1102793	Binding	Inhibition of DYRK4 at 10 uM	Discovery of N-substituted pyridinones as potent and selective inhibitors of p38 kinase. — Bioorg Med Chem Lett
CHEMBL1963797	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: DYRK4	PubChem BioAssay data set

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1QK	Abcam HeLa DYRK4 KO	Cancer cell line	Female
CVCL_SL28	HAP1 DYRK4 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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