CLK4

Summary

CLK4 (CDC like kinase 4, HGNC:13659) is a protein-coding gene on chromosome 5q35.3, encoding Dual specificity protein kinase CLK4 (Q9HAZ1). Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates.

The protein encoded by this gene belongs to the CDC2-like protein kinase (CLK) family. This protein kinase can interact with and phosphorylate the serine- and arginine-rich (SR) proteins, which are known to play an important role in the formation of spliceosomes, and thus may be involved in the regulation of alternative splicing. Studies in the Israeli sand rat Psammomys obesus suggested that the ubiquitin-like 5 (UBL5/BEACON), a highly conserved ubiquitin-like protein, may interact with and regulate the activity of this kinase. Multiple alternatively spliced transcript variants have been observed, but the full-length natures of which have not yet been determined.

Source: NCBI Gene 57396 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 68 total — 1 pathogenic
• Druggable target: yes — 60 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_020666

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13659
Approved symbol	CLK4
Name	CDC like kinase 4
Location	5q35.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113240
Ensembl biotype	protein_coding
OMIM	607969
Entrez	57396

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 7 retained_intron, 5 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000316308, ENST00000519132, ENST00000519583, ENST00000520126, ENST00000520199, ENST00000520878, ENST00000520909, ENST00000520957, ENST00000521621, ENST00000522136, ENST00000522556, ENST00000522749, ENST00000523013, ENST00000867301, ENST00000867302, ENST00000921422

RefSeq mRNA: 1 — MANE Select: NM_020666 NM_020666

CCDS: CCDS4437

Canonical transcript exons

ENST00000316308 — 13 exons

Exon	Start	End
ENSE00002099854	178626946	178627050
ENSE00003463702	178605303	178605382
ENSE00003463872	178616882	178616948
ENSE00003473654	178613727	178613843
ENSE00003503262	178603844	178603934
ENSE00003533642	178617344	178617434
ENSE00003551172	178623256	178623416
ENSE00003554839	178612416	178612545
ENSE00003559015	178602664	178603757
ENSE00003568047	178613473	178613639
ENSE00003600092	178618556	178618778
ENSE00003635129	178612796	178612890
ENSE00003639528	178608376	178608458

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.57.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4036 / max 574.1446, expressed in 1799 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65177	19.1509	1794
65178	1.2331	705
65179	0.0196	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	98.57	gold quality
cerebellar cortex	UBERON:0002129	98.55	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.51	gold quality
cerebellum	UBERON:0002037	98.40	gold quality
tibia	UBERON:0000979	95.20	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.15	gold quality
sperm	CL:0000019	95.08	gold quality
renal medulla	UBERON:0000362	95.06	gold quality
calcaneal tendon	UBERON:0003701	95.05	gold quality
body of pancreas	UBERON:0001150	94.92	gold quality
urethra	UBERON:0000057	94.65	gold quality
pylorus	UBERON:0001166	94.38	gold quality
epithelium of nasopharynx	UBERON:0001951	94.27	gold quality
corpus callosum	UBERON:0002336	94.21	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	94.21	gold quality
visceral pleura	UBERON:0002401	94.16	gold quality
mucosa of stomach	UBERON:0001199	94.07	gold quality
cerebellar vermis	UBERON:0004720	94.03	gold quality
superior surface of tongue	UBERON:0007371	94.02	gold quality
tibial nerve	UBERON:0001323	93.99	gold quality
male germ cell	CL:0000015	93.86	gold quality
cranial nerve II	UBERON:0000941	93.85	gold quality
lymph node	UBERON:0000029	93.67	gold quality
trigeminal ganglion	UBERON:0001675	93.58	gold quality
right uterine tube	UBERON:0001302	93.23	gold quality
bronchial epithelial cell	CL:0002328	93.12	gold quality
cardia of stomach	UBERON:0001162	93.11	gold quality
pericardium	UBERON:0002407	93.09	gold quality
fundus of stomach	UBERON:0001160	93.04	gold quality
primary visual cortex	UBERON:0002436	93.03	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	438.46
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

85 targeting CLK4, 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-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-548J-3P	99.94	72.61	4881

Literature-anchored findings (GeneRIF, showing 2)

• Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells. (PMID:19168442)
• Clk1, Clk2 and Clk4 prevent chromatin breakage by regulating the Aurora B-dependent abscission checkpoint. (PMID:27126587)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	clk4a	ENSDARG00000089372
mus_musculus	Clk4	ENSMUSG00000020385
rattus_norvegicus	Clk4	ENSRNOG00000003714
drosophila_melanogaster	mnb	FBGN0259168
caenorhabditis_elegans		WBGENE00001994
caenorhabditis_elegans		WBGENE00003149
caenorhabditis_elegans		WBGENE00013727
caenorhabditis_elegans		WBGENE00185089

Paralogs (12): DYRK4 (ENSG00000010219), CLK1 (ENSG00000013441), HIPK2 (ENSG00000064393), DYRK1B (ENSG00000105204), HIPK3 (ENSG00000110422), DYRK2 (ENSG00000127334), DYRK3 (ENSG00000143479), DYRK1A (ENSG00000157540), HIPK4 (ENSG00000160396), HIPK1 (ENSG00000163349), CLK2 (ENSG00000176444), CLK3 (ENSG00000179335)

Protein

Protein identifiers

Dual specificity protein kinase CLK4 — Q9HAZ1 (reviewed: Q9HAZ1)

Alternative names: CDC-like kinase 4

All UniProt accessions (5): Q9HAZ1, E7ES88, E7EWJ6, Q68D95, Q6P090

UniProt curated annotations — full annotation on UniProt →

Function. Dual specificity kinase acting on both serine/threonine and tyrosine-containing substrates. Phosphorylates serine- and arginine-rich (SR) proteins of the spliceosomal complex and may be a constituent of a network of regulatory mechanisms that enable SR proteins to control RNA splicing. Phosphorylates SRSF1 and SRSF3. Required for the regulation of alternative splicing of MAPT/TAU. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells.

Subunit / interactions. Interacts with UBL5.

Subcellular location. Nucleus.

Tissue specificity. Expressed in liver, kidney, heart, muscle, brain and endothelial cells.

Post-translational modifications. Autophosphorylates on all three types of residues.

Activity regulation. TG003 inhibits its kinase activity and affects the regulation of alternative splicing mediated by phosphorylation of SR proteins.

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

RefSeq proteins (1): NP_065717* (*=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
IPR051175	CLK_kinases	Family

Pfam: PF00069

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 (45 total): helix 16, strand 10, turn 4, compositionally biased region 3, modified residue 2, sequence variant 2, region of interest 2, binding site 2, chain 1, domain 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6FYV	X-RAY DIFFRACTION	2.46

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HAZ1-F1	78.48	0.67

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): 286 (proton acceptor)

Ligand- & substrate-binding residues (2): 165–173; 189

Post-translational modifications (2): 136, 138

Mutagenesis-validated functional residues (1):

Position	Phenotype
189	loss of function.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 184 (showing top): GCM_ZNF198, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, FISCHER_G2_M_CELL_CYCLE, GOBP_RNA_SPLICING, ATTCTTT_MIR186, LEE_METASTASIS_AND_ALTERNATIVE_SPLICING_DN, BYSTROEM_CORRELATED_WITH_IL5_DN, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, GOBP_REGULATION_OF_RNA_SPLICING, GCCATNTTG_YY1_Q6, CHEN_HOXA5_TARGETS_9HR_UP, GRAHAM_CML_QUIESCENT_VS_NORMAL_DIVIDING_UP, GOMF_PROTEIN_KINASE_ACTIVITY, GEORGES_TARGETS_OF_MIR192_AND_MIR215, GOMF_KINASE_ACTIVITY

GO Biological Process (2): regulation of RNA splicing (GO:0043484), protein phosphorylation (GO:0006468)

GO Molecular Function (10): 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 kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein kinase activity	4
RNA splicing	1
regulation of gene expression	1
regulation of primary metabolic process	1
phosphorylation	1
protein modification process	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate 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

Protein interactions and networks

STRING

1048 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLK4	MBP	P02686	658
CLK4	H2BC21	Q16778	549
CLK4	SRSF6	Q13247	495
CLK4	SLC13A5	Q86YT5	462
CLK4	RBFOX2	O43251	461
CLK4	SRSF4	Q08170	452
CLK4	SRSF5	Q13243	435
CLK4	SRSF1	Q07955	432
CLK4	SRSF7	Q16629	423
CLK4	LGALS4	P56470	419
CLK4	ANHX	E9PGG2	418
CLK4	SRSF3	P23152	400
CLK4	TPRX1	Q8N7U7	373
CLK4	IRX1	P78414	368
CLK4	ARGFX	A6NJG6	366

IntAct

54 interactions, top by confidence:

A	B	Type	Score
CLK4	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-7	CLK4	psi-mi:“MI:0915”(physical association)	0.720
	CLK4	psi-mi:“MI:0915”(physical association)	0.560
CLK4	KPNA1	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-8	CLK4	psi-mi:“MI:0915”(physical association)	0.560
CLK4	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
CLK4	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
KPNA1	CLK4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-6	CLK4	psi-mi:“MI:0915”(physical association)	0.560
SRRM4	CLK4	psi-mi:“MI:0915”(physical association)	0.560
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
CLK4	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
RNF181	CLK4	psi-mi:“MI:0915”(physical association)	0.370
CLK4	UBL5	psi-mi:“MI:0915”(physical association)	0.370
RGMA	BDP1	psi-mi:“MI:0914”(association)	0.350
PIM2	NUP98	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
JMJD6	U2SURP	psi-mi:“MI:0914”(association)	0.350
N	RBM47	psi-mi:“MI:0914”(association)	0.350

BioGRID (60): CLK4 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), CLK4 (Affinity Capture-RNA), CLK4 (Affinity Capture-MS), CLK4 (Affinity Capture-MS), CLK4 (Affinity Capture-MS), CLK4 (Affinity Capture-MS), CLK4 (Affinity Capture-MS), CLK4 (Two-hybrid), CLK4 (Two-hybrid), CLK4 (Reconstituted Complex), SRRM4 (Two-hybrid)

ESM2 similar proteins: A1CL96, A1D624, A2X0M1, A2Y4B6, O35491, O35492, O35493, O35831, O35832, O44514, P22518, P46551, P49759, P49760, P49761, P51566, P51567, P83099, Q00536, Q00537, Q04735, Q09437, Q0CQK1, Q0E459, Q11179, Q23357, Q3SX21, Q4FCZ5, Q4I5U9, Q4WYR6, Q53N72, Q5BAE1, Q5SN53, Q5VP69, Q5Z9J0, Q5ZCI1, Q5ZIU3, Q63117, Q63686, Q67C40

Diamond homologs: A1CAF0, A1CPG7, A1D2C9, A1DES4, A2QN07, A2QRF6, A3EZ55, A4L9P5, A8WJR8, A8X4H1, B0XR80, B0Y462, G1XJZ4, M1T7M3, O35491, O35492, O35493, O43781, O88850, O88904, P0C431, P0CP68, P0CP69, P14680, P22518, P49657, P49759, P49760, P49761, P49762, P50613, P51566, P51567, P51568, P83102, Q03147, Q07538, Q08DZ2, Q09690, Q09815

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CLK4	down-regulates	ABL1	phosphorylation
CLK4	“down-regulates quantity by destabilization”	MITF	phosphorylation
CLK4	“up-regulates activity”	NR5A1	phosphorylation
CLK4	“up-regulates activity”	SRSF1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 35 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA Splicing	5	21.1×	6e-04
Processing of Capped Intron-Containing Pre-mRNA	5	15.8×	8e-04
mRNA Splicing - Major Pathway	6	12.6×	6e-04
Keratinization	5	10.7×	2e-03
Metabolism of RNA	6	9.6×	1e-03
Dengue Virus-Host Interactions	5	8.8×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	5	43.6×	2e-05
RNA splicing	6	18.9×	8e-05
mRNA processing	5	14.1×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	49
Likely benign	1
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
187821	GRCh37/hg19 5q35.2-35.3(chr5:174397487-180686444)x1	Pathogenic

SpliceAI

1850 predictions. Top by Δscore:

Variant	Effect	Δscore
5:178605298:CATA:C	donor_loss	1.0000
5:178605299:ATAC:A	donor_loss	1.0000
5:178605300:TA:T	donor_loss	1.0000
5:178605302:C:CA	donor_loss	1.0000
5:178605378:TGAGT:T	acceptor_gain	1.0000
5:178605379:GAGT:G	acceptor_gain	1.0000
5:178605380:AGT:A	acceptor_gain	1.0000
5:178605381:GT:G	acceptor_gain	1.0000
5:178605382:TCT:T	acceptor_loss	1.0000
5:178605383:C:CC	acceptor_gain	1.0000
5:178605383:CTAAA:C	acceptor_loss	1.0000
5:178605389:CA:C	acceptor_gain	1.0000
5:178605390:A:C	acceptor_gain	1.0000
5:178605941:T:C	acceptor_gain	1.0000
5:178612414:AC:A	donor_gain	1.0000
5:178612415:CC:C	donor_gain	1.0000
5:178612541:CGTTT:C	acceptor_gain	1.0000
5:178612891:C:CC	acceptor_gain	1.0000
5:178613467:ACTT:A	donor_loss	1.0000
5:178613469:TTA:T	donor_loss	1.0000
5:178613470:TA:T	donor_loss	1.0000
5:178613471:A:AC	donor_gain	1.0000
5:178613471:A:T	donor_loss	1.0000
5:178613472:C:CC	donor_gain	1.0000
5:178613472:CA:C	donor_gain	1.0000
5:178613472:CAA:C	donor_gain	1.0000
5:178613472:CAAT:C	donor_gain	1.0000
5:178613472:CAATT:C	donor_gain	1.0000
5:178613635:ATCGG:A	acceptor_gain	1.0000
5:178613636:TCGG:T	acceptor_gain	1.0000

AlphaMissense

3247 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:178603674:T:A	R463S	1.000
5:178603674:T:G	R463S	1.000
5:178603675:C:G	R463T	1.000
5:178603869:A:T	V427D	1.000
5:178603898:C:A	W417C	1.000
5:178603898:C:G	W417C	1.000
5:178603900:A:G	W417R	1.000
5:178603900:A:T	W417R	1.000
5:178605351:A:C	M389R	1.000
5:178605360:A:G	L386P	1.000
5:178605360:A:T	L386Q	1.000
5:178605363:T:C	H385R	1.000
5:178605364:G:C	H385D	1.000
5:178608379:A:C	F377L	1.000
5:178608379:A:T	F377L	1.000
5:178608380:A:G	F377S	1.000
5:178608381:A:G	F377L	1.000
5:178608392:C:A	G373V	1.000
5:178608392:C:T	G373D	1.000
5:178608393:C:G	G373R	1.000
5:178608415:G:C	C365W	1.000
5:178608416:C:T	C365Y	1.000
5:178608417:A:G	C365R	1.000
5:178608419:C:T	G364D	1.000
5:178608420:C:G	G364R	1.000
5:178608424:G:C	S362R	1.000
5:178608424:G:T	S362R	1.000
5:178608426:T:G	S362R	1.000
5:178608427:C:A	W361C	1.000
5:178608427:C:G	W361C	1.000

dbSNP variants (sampled 300 via entrez): RS1000015894 (5:178610827 T>C), RS1000372000 (5:178628204 A>G), RS1000742628 (5:178618741 A>G), RS1000925304 (5:178625602 T>C), RS1001024873 (5:178618154 G>A), RS1001080239 (5:178617955 A>G,T), RS1001199207 (5:178619144 T>G), RS1001300691 (5:178624443 C>T), RS1001383361 (5:178607811 T>C), RS1001693464 (5:178615275 C>A), RS1001745895 (5:178615053 G>C), RS1001875167 (5:178626541 C>T), RS1001902404 (5:178623172 T>G), RS1001952551 (5:178604743 A>C), RS1001965550 (5:178621655 G>A)

Disease associations

OMIM: gene MIM:607969 | 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
GCST002828_26	Urate levels in obese individuals	4.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004531	urate measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL4106176 (PROTEIN FAMILY), CHEMBL4203 (SINGLE PROTEIN), CHEMBL5291951 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

60 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 468,961 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL189963	PALBOCICLIB	4	13,102
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL2325741	CAPIVASERTIB	4	2,157
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL31	GATIFLOXACIN	4	25,151
CHEMBL3301610	ABEMACICLIB	4	7,045
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL941	IMATINIB	4	111,611
CHEMBL140	CURCUMIN	3	93,882
CHEMBL1879463	DACTOLISIB	3	7,988
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL300138	ENZASTAURIN	3	3,209
CHEMBL38380	FASUDIL	3	11,953
CHEMBL4297639	LORECIVIVINT	3
CHEMBL483158	ALISERTIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3
CHEMBL1230165	SILMITASERTIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL124660	TANDUTINIB	2
CHEMBL14762	SELICICLIB	2
CHEMBL1614713	CC-401	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — CLK family

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

Ligand	Action	Affinity	Parameter
compound 17 [PMID: 23642479]	Inhibition	8.4	pIC50
MW01	Inhibition	7.85	pIC50
compound 3b [PMID: 23454515]	Inhibition	7.21	pIC50
ML315	Inhibition	7.17	pIC50
kinase inhibitor 2 [PMID: 30199702]	Inhibition	7.05	pIC50
MW05	Inhibition	6.51	pIC50
tomivosertib	Inhibition	6.1	pIC50

Binding affinities (BindingDB)

13 measured of 13 human assays (13 total across all organisms); most potent 13 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
PKC-412	KD	190 nM
1-[4-(3-amino-1H-indazol-4-yl)phenyl]-3-(2-fluoro-5-methyl-phenyl)urea	KD	450 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.1^{7,14}.0^{2,6}.0^{8,13}.0^{22,27}]nonacosa-1(28),2(6),7(29),8(13),9,11,22(27),23,25-nonaene-3,5-dione	KD	700 nM
4-[6-methoxy-7-(3-piperidin-1-ylpropoxy)quinazolin-4-yl]-N-(4-propan-2-yloxyphenyl)piperazine-1-carboxamide	KD	740 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
BMS-387072	KD	1800 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

2000 potent at pChembl≥5 of 3113 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.50	Ki	0.3162	nM	CHEMBL1980407
9.28	Kd	0.53	nM	CHEMBL379218
9.21	Kd	0.61	nM	CHEMBL4797564
9.21	IC50	0.61	nM	CHEMBL4797564
9.20	Ki	0.631	nM	CHEMBL1965660
9.20	Ki	0.631	nM	CHEMBL2007574
9.10	Kd	0.8	nM	CHEMBL5093650
9.00	IC50	1	nM	CIRTUVIVINT
9.00	IC50	1	nM	CHEMBL5428651
9.00	IC50	1	nM	CHEMBL5404544
9.00	IC50	1	nM	CHEMBL5405233
9.00	Ki	1	nM	CHEMBL1981133
9.00	Ki	1	nM	CHEMBL1977138
9.00	Ki	1	nM	CHEMBL1973720
8.90	Ki	1.259	nM	CHEMBL1996980
8.90	Ki	1.259	nM	CHEMBL1990162
8.80	Ki	1.585	nM	CHEMBL1987448
8.80	Ki	1.585	nM	CHEMBL1983575
8.70	Kd	2	nM	RGB-286638
8.70	IC50	1.98	nM	T3-CLK
8.70	IC50	2	nM	CHEMBL5404416
8.70	IC50	2	nM	CHEMBL5414514
8.70	IC50	2	nM	CHEMBL5405059
8.70	IC50	2	nM	CHEMBL5417147
8.70	IC50	2	nM	CHEMBL5422654
8.70	IC50	2	nM	CHEMBL5418722
8.70	IC50	2	nM	CHEMBL5409574
8.70	IC50	2	nM	CHEMBL5412565
8.70	Ki	1.995	nM	CHEMBL1980995
8.70	Ki	1.995	nM	CHEMBL1980562
8.70	Ki	1.995	nM	CHEMBL1982271
8.70	Ki	1.995	nM	CHEMBL1967252
8.68	IC50	2.1	nM	CHEMBL5429691
8.67	IC50	2.16	nM	STAUROSPORINE
8.64	IC50	2.3	nM	CHEMBL4082113
8.60	Ki	2.512	nM	CHEMBL1969151
8.60	Ki	2.512	nM	CHEMBL2002613
8.59	IC50	2.6	nM	SILMITASERTIB
8.57	IC50	2.7	nM	SEL-120 FREE BASE
8.54	IC50	2.9	nM	CHEMBL5561973
8.52	IC50	3	nM	CHEMBL5438293
8.52	IC50	3	nM	CHEMBL5420645
8.52	IC50	3	nM	CHEMBL5427398
8.52	IC50	3	nM	CHEMBL5396550
8.52	IC50	3	nM	CHEMBL5437778
8.52	IC50	3	nM	CHEMBL5440511
8.52	IC50	3	nM	CHEMBL5401116
8.52	IC50	3	nM	CHEMBL5426735
8.52	IC50	3	nM	CHEMBL5429404
8.52	Kd	3	nM	LESTAURTINIB

PubChem BioAssay actives

658 with measured affinity, of 2353 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
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	625125: Binding constant for CLK4 kinase domain	kd	0.0005	uM
2-N-methyl-4-N-(pyrimidin-2-ylmethyl)-5-quinolin-6-yl-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1851267: Binding affinity to CLK4 (unknown origin) assessed as dissociation constant	kd	0.0006	uM
5-(2-amino-4-pyridinyl)-N-[(2,6-difluorophenyl)methyl]-2-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine	1812182: Inhibition of human partial length CLK4 (R135/K481) expressed in bacterial system by DiscoveryX Kinomescan binding assay	kd	0.0008	uM
2-(4-methylpiperazin-1-yl)-N-[6-(1-methylpyrazol-4-yl)isoquinolin-3-yl]pyridine-4-carboxamide	1851260: Inhibition of CLK4 (unknown origin) by Z’-LYTE assay	ic50	0.0010	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(5-hydroxy-2-adamantyl)imino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP 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-[(1R)-2-hydroxy-1-phenylethyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP 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-(thian-3-ylimino)imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0010	uM
1-[3-[4-[[4-(2-methoxyethyl)piperazin-1-yl]methyl]phenyl]-4-oxo-1H-indeno[2,1-d]pyrazol-5-yl]-3-morpholin-4-ylurea	1424958: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0020	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,2S)-2-hydroxycycloheptyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP 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-[(3-methoxy-1-adamantyl)imino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP 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-[(3-hydroxy-1-adamantyl)imino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]cyclopropanecarboxamide	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]acetamide	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
N-[3-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-1-adamantyl]methanesulfonamide	2010389: Inhibition of human CLK4 using MBP 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-[[3-(dimethylamino)-1-adamantyl]imino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
2-(1-adamantylamino)-5-[(E)-benzimidazol-5-ylidenemethyl]-1H-imidazol-4-ol	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0020	uM
5-[(E)-benzimidazol-5-ylidenemethyl]-2-[[(2R)-1-methoxy-4-methylpentan-2-yl]amino]-3-methylimidazol-4-ol	2024435: Inhibition of human CLK4 assessed as incorporation of 33Pi using [gamma-33P]-ATP measured after 60 mins by microplate scintillation counting based radiometric analysis	ic50	0.0021	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	2110577: Inhibition of CLK4 (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	0.0022	uM
N-[(3-fluorophenyl)methyl]-5-methoxy-N-methyl-1-benzothiophene-2-carboxamide	1933994: Inhibition of human CLK4	ic50	0.0023	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1947681: Inhibition of recombinant human CLK4 expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0026	uM
6,7-dibromo-5-methyl-2-piperazin-1-yl-1,3-diazatricyclo[6.3.1.04,12]dodeca-2,4,6,8(12)-tetraene	2070981: Inhibition of CLK4 (unknown origin) by ADP-Glo assay	ic50	0.0027	uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole	2070981: Inhibition of CLK4 (unknown origin) by ADP-Glo assay	ic50	0.0029	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507880: Binding affinity to CLK4	kd	0.0030	uM
methyl (2S)-2-[[(4Z)-4-(1,3-benzothiazol-6-ylmethylidene)-5-oxoimidazolidin-2-ylidene]amino]-3-hydroxybutanoate	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[(1S,2S)-2-hydroxy-2,3-dihydro-1H-inden-1-yl]imino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocycloheptyl)iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocyclopentyl)iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-fluoro-4-methylpentan-2-yl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,3R)-3-hydroxycycloheptyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-2-(1-adamantylimino)-5-[(3-methylbenzimidazol-5-yl)methylidene]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzoxazol-6-ylmethylidene)imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,3R)-3-methoxycycloheptyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0030	uM
(2S)-4-methyl-1-[[5-[3-(2-thiophen-3-ylethynyl)-2H-indazol-5-yl]-3-pyridinyl]oxy]pentan-2-amine	2082336: Inhibition of CLK4 (unknown origin) incubated for 10 mins in presence of ATP	ic50	0.0032	uM
8-[1-[3-(dimethylamino)propyl]pyrazol-4-yl]-9-ethyl-6,6-dimethyl-11-oxo-5H-benzo[b]carbazole-3-carbonitrile	1267057: Inhibition of CLK4 (unknown origin)	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[[2-(trifluoromethyl)phenyl]methylimino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(pyridin-3-ylmethylimino)imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1S,4S)-4-hydroxycycloheptyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2S)-1-fluoro-4-methylpentan-2-yl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R)-2-methoxy-1-phenylethyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3,5,7-trifluoro-1-adamantyl)imino]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(3,3-difluorocyclohexyl)iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(1,4-dioxepan-6-ylimino)imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-(2,2-difluorocyclohexyl)iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(2R)-1-ethoxy-4-methylpentan-2-yl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,3S)-3-hydroxycycloheptyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-2-cycloheptylimino-5-[(3-methylbenzimidazol-5-yl)methylidene]imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
2-(1-adamantylamino)-5-[(E)-indazol-5-ylidenemethyl]-1H-imidazol-4-ol	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,3R)-3-methoxycyclohexyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(1R,4R)-4-hydroxycycloheptyl]iminoimidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM
(5Z)-2-(1-adamantylimino)-5-(1,3-benzodioxol-5-ylmethylidene)imidazolidin-4-one	2010389: Inhibition of human CLK4 using MBP and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0040	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression	4
sodium arsenite	affects expression, decreases expression	3
Cyclosporine	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
dicrotophos	decreases expression	1
geldanamycin	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	increases oxidation, increases abundance, affects cotreatment	1
afimoxifene	decreases expression, decreases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, increases expression	1
cupric chloride	decreases expression	1
5-iodotubercidin	decreases activity	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	decreases expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	increases expression	1
abrine	increases expression	1
jinfukang	decreases expression, affects cotreatment	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	increases expression	1
Acrolein	increases abundance, affects cotreatment, increases oxidation	1

ChEMBL screening assays

346 unique, capped per target: 333 binding, 13 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4016847	Binding	Inhibition of CLK1/4 in human T24 cells assessed as down regulation of EGFR expression at 10 uM after 3 days by Western blot analysis relative to control	Development of Selective Clk1 and -4 Inhibitors for Cellular Depletion of Cancer-Relevant Proteins. — J Med Chem
CHEMBL1613824	Functional	PUBCHEM_BIOASSAY: Confirmation Assay for Inhibitors of CDC-like Kinase 4 (ADP-FP Assay). (Class of assay: confirmatory) [Related pubchem assays: 1771, 1970, 1795, 1969, 1379, 1770 ]	PubChem BioAssay data set

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1NJ	Abcam HeLa CLK4 KO	Cancer cell line	Female
CVCL_SJ24	HAP1 CLK4 (-) 1	Cancer cell line	Male
CVCL_SJ25	HAP1 CLK4 (-) 2	Cancer cell line	Male
CVCL_SJ26	HAP1 CLK4 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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