CSNK1E

Summary

CSNK1E (casein kinase 1 epsilon, HGNC:2453) is a protein-coding gene on chromosome 22q13.1, encoding Casein kinase I isoform epsilon (P49674). Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates.

The protein encoded by this gene is a serine/threonine protein kinase and a member of the casein kinase I protein family, whose members have been implicated in the control of cytoplasmic and nuclear processes, including DNA replication and repair. The encoded protein is found in the cytoplasm as a monomer and can phosphorylate a variety of proteins, including itself. This protein has been shown to phosphorylate period, a circadian rhythm protein. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 1454 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Limited, GenCC)
• GWAS associations: 2
• Clinical variants (ClinVar): 51 total — 1 pathogenic
• Druggable target: yes — 37 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_152221

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2453
Approved symbol	CSNK1E
Name	casein kinase 1 epsilon
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Aliases	HCKIE, CKIE, CKIepsilon
Ensembl gene	ENSG00000213923
Ensembl biotype	protein_coding
OMIM	600863
Entrez	1454

Gene structure

Transcript identifiers

Ensembl transcripts: 33 — 30 protein_coding, 2 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000359867, ENST00000366216, ENST00000396832, ENST00000403904, ENST00000405675, ENST00000413574, ENST00000430335, ENST00000431611, ENST00000431632, ENST00000442216, ENST00000451964, ENST00000494610, ENST00000495232, ENST00000498529, ENST00000612795, ENST00000887325, ENST00000887326, ENST00000887327, ENST00000887328, ENST00000922680, ENST00000922681, ENST00000922682, ENST00000922683, ENST00000922684, ENST00000922685, ENST00000922686, ENST00000922687, ENST00000967530, ENST00000967531, ENST00000967532, ENST00000967533, ENST00000967534, ENST00000967535

RefSeq mRNA: 2 — MANE Select: NM_152221 NM_001894, NM_152221

Canonical transcript exons

ENST00000396832 — 11 exons

Exon	Start	End
ENSE00001526409	38317160	38317433
ENSE00001840267	38290691	38291938
ENSE00003802249	38298786	38298934
ENSE00003803453	38294342	38294534
ENSE00003805672	38300724	38300952
ENSE00003806643	38299895	38300065
ENSE00003810751	38294109	38294248
ENSE00003890577	38293255	38293319
ENSE00003893001	38314082	38314169
ENSE00003894674	38303138	38303248
ENSE00003895888	38302861	38303009

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.2242 / max 271.3708, expressed in 1780 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194150	8.0218	1670
194147	1.8231	1109
194148	1.4139	1005
194149	1.3687	954
194144	1.2732	808
194139	1.2581	665
194141	0.8005	515
194142	0.5950	350
194146	0.5058	296
209474	0.4969	275

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.16	gold quality
ganglionic eminence	UBERON:0004023	99.15	gold quality
left ovary	UBERON:0002119	98.45	gold quality
ventricular zone	UBERON:0003053	98.44	gold quality
right uterine tube	UBERON:0001302	98.42	gold quality
endocervix	UBERON:0000458	98.37	gold quality
body of uterus	UBERON:0009853	98.29	gold quality
right ovary	UBERON:0002118	98.26	gold quality
stromal cell of endometrium	CL:0002255	98.20	gold quality
adenohypophysis	UBERON:0002196	98.17	gold quality
skin of leg	UBERON:0001511	98.16	gold quality
ectocervix	UBERON:0012249	98.15	gold quality
tibial nerve	UBERON:0001323	98.14	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.07	gold quality
mucosa of stomach	UBERON:0001199	97.95	gold quality
lower esophagus mucosa	UBERON:0035834	97.94	gold quality
right lung	UBERON:0002167	97.93	gold quality
cerebellar hemisphere	UBERON:0002245	97.84	gold quality
cerebellar cortex	UBERON:0002129	97.72	gold quality
left uterine tube	UBERON:0001303	97.70	gold quality
skin of abdomen	UBERON:0001416	97.70	gold quality
minor salivary gland	UBERON:0001830	97.68	gold quality
omental fat pad	UBERON:0010414	97.52	gold quality
tibial artery	UBERON:0007610	97.51	gold quality
popliteal artery	UBERON:0002250	97.50	gold quality
peritoneum	UBERON:0002358	97.47	gold quality
muscle layer of sigmoid colon	UBERON:0035805	97.38	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.34	gold quality
body of pancreas	UBERON:0001150	97.33	gold quality
aorta	UBERON:0000947	97.31	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.49

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BMAL1

miRNA regulators (miRDB)

58 targeting CSNK1E, 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-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-182-5P	99.87	74.03	2589
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4470	99.66	69.35	1767

Literature-anchored findings (GeneRIF, showing 40)

• The circadian regulatory proteins BMAL1 and cryptochromes are substrates of casein kinase Iepsilon. (PMID:11875063)
• CKI epsilon-dependent phosphorylation of Dvl enhances the formation of a complex of Dvl-1 with Frat-1 and this complex leads to the activation of Wnt-3a-induced accumulation of beta-catenin (PMID:12556519)
• casein kinase I epsilon activity is regulated by Wnt signaling (PMID:14722104)
• These results suggest that CKIepsilon plays a ligand-dependent, differential, and dual regulatory role within the TGF-beta signaling pathway. (PMID:15133026)
• the N408 allele in casein kinase 1, epsilon plays a protective role in the development of delayed sleep phase syndrome (PMID:15187983)
• A negative regulatory function of CK1 in the Wnt signalling pathway, where CK1 acts as a negative regulator of the LEF-1/beta-catenin transcription complex, thereby protecting cells from development of cancer. (PMID:15747065)
• CKIepsilon inhibition also slows the degradation of PER2 in cells (PMID:15767683)
• CK1epsilon and CK1gamma2 were found to bind to Per1 and to promote its degradation (PMID:15917222)
• CKIepsilon-induced down-regulation of PI3K/Akt signaling through PTEN leads to amplified sensitivity to apoptosis. (PMID:16274701)
• active CKIepsilon generation may induce a negative feedback loop by phosphorylation of sites on LRP5/6 that modulate axin binding and hence beta-catenin degradation (PMID:16513652)
• These findings suggest that granulovacuolar and neurofibrillary lesions occupy separate populations of neurons, and implicate CK1 isoforms in the generation of lesion-associated phosphoepitopes. (PMID:16557393)
• CKI epsilon is a novel occludin kinase that may be important for the regulation of occludin. (PMID:16616143)
• CKI epsilon(tau) is a highly specific gain-of-function mutation that increases in vivo phosphorylation and degradation of the circadian regulators period (PER)1 and PER2. (PMID:16818876)
• Signal transduction pathway is defined downstream of CCK2 receptor showing that CK1 delta and epsilon phosphorylate PKD2 at 3 sites, resulting in nuclear accumulation of PKD2 and phosphorylation of nuclear PKD2 substrates in human gastric cancer cells. (PMID:17962809)
• A multi-locus interaction between rs6442925 in the 5’ upstream of BHLHB2, rs1534891 in CSNK1E, and rs534654 near the 3’ end of the CLOCK gene, however, is significantly associated with bipolar disorder (PMID:18228528)
• human casein kinase 1 epsilon cannot replace the activity of dbt in flies despite the high degree of similarity in primary sequence and kinase function (PMID:18258753)
• The results suggest that CKIepsilon is a new positive regulator of the Akt pathway. Here we propose that, rather than inhibiting PTEN function, CKIepsilon positively regulates Akt possibly by inhibiting Protein Phosphatase 2A (PP2A). (PMID:18262492)
• CK1 epsilon(tau), as a gain-of-function mutation, acts at a specific circadian phase to promote degradation of PERIOD proteins and thereby accelerate the mammalian clockwork in brain and periphery. (PMID:18400165)
• These data support the hypothesis that circadian clock genes can control the cell cycle and cell survival signaling, and emphasize a central role of CK1epsilon and PERIOD2 in linking these systems. (PMID:18518968)
• DATA show that Casein kinase I epsilon (CKIvarepsilon) N408 allele is very rare in the Brazilian population and is not involved in susceptibility to circadian rhythm sleep disorders. (PMID:18571740)
• Variations in circadian genes are associated with serum levels of androgens and IGF markers, particularly CSNK1E rs1005473:A>C. (PMID:18990770)
• Results suggest that having a genetic variant of the casein kinase 1 epsilon gene did not affect susceptibility to methamphetamine dependence or psychosis, at least in a Japanese population. (PMID:18991847)
• Casein kinase I epsilon is an upstream kinase regulating in vivo phosphorylation of topoisomerase IIalpha at Ser-1106. (PMID:19043076)
• The degradation rate of PER2, which is regulated by CKIepsilon/delta-dependent phosphorylation, was temperature-insensitive in living clock cells. (PMID:19805222)
• identified CK1delta/epsilon as new regulators of YAP and uncovered an intricate mechanism of YAP regulation (PMID:20048001)
• Data show that expression of CK1epsilon is able to promote oncogenic transformation of human cells in a beta-catenin-dependent manner. (PMID:20126544)
• Mutations in CK1epsilon inhibit Wnt/beta-catenin and activate the Wnt/Rac1/JNK and NFAT pathways to decrease cell adhesion and promote cell migration in breast cancer. (PMID:20507565)
• Depletion of p120-catenin abolishes CK1epsilon binding to LRP5/6 and prevents CK1epsilon activation upon Wnt3a stimulation. (PMID:20940130)
• CK1epsilon regulates the cellular levels of Cdc25A in parallel with Chk1-dependent Cdc25A degradation, contributing to the precise control of cell division. (PMID:21252624)
• No evidence is provided for the association between CK1epsilon gene and personality traits in healthy Chinese-Han subjects. (PMID:22113361)
• A genetic variant in the Csnk1epsilon gene significantly enhances the probability of schizophrenia in the Chinese Han population. (PMID:22367616)
• Casein kinase 1 proteomics reveal prohibitin 2 function in molecular clock (PMID:22384121)
• Identification of a novel Wnt5a-CK1varepsilon-Dvl2-Plk1-mediated primary cilia disassembly pathway. (PMID:22609948)
• In the context of ovarian cancer, the interaction between CKIepsilon and ANT2 mediates pathogenic signalling that is distinct from the canonical Wnt/beta-catenin pathway and is essential for cell proliferation and is clinically associated with poor survival. (PMID:22707389)
• These results do not support that genetic variation in CSNK1D and CSNK1E is a susceptibility factor for major psychiatric disorders in the Japanese population. (PMID:22981886)
• study identified DDX3 as a regulator of the Wnt-beta-catenin network, where it acts as a regulatory subunit of CK1epsilon: in a Wnt-dependent manner, DDX3 binds CK1epsilon and directly stimulates its kinase activity and promotes phosphorylation of the scaffold protein dishevelled (PMID:23413191)
• MST1 still inhibited the Wnt3A-induced phosphorylation of DVL2 (dishevelled 2) and Wnt/beta-catenin signalling by disturbing the interaction of DVL2 and CK1epsilon (PMID:24180524)
• Csnk1epsilon gene polymorphism (rs135745), especially the G allele, maybe associated with heroin dependence in the Han Chinese. (PMID:24338102)
• CK1delta and CK1epsilon play a decisive role in triggering late steps of pre-40S maturation that are required for acquisition of functionality of 40S ribosomal subunits in protein translation. (PMID:24424021)
• The loss of cytoplasmic CK1epsilon expression is greatly associated with poor survival and might be an adverse survival factor. (PMID:24557581)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Csnk1e	ENSMUSG00000022433
rattus_norvegicus	Csnk1e	ENSRNOG00000013076
drosophila_melanogaster	dco	FBGN0002413
caenorhabditis_elegans		WBGENE00002203

Paralogs (12): VRK2 (ENSG00000028116), CDC7 (ENSG00000097046), VRK1 (ENSG00000100749), VRK3 (ENSG00000105053), CSNK1A1 (ENSG00000113712), TTBK2 (ENSG00000128881), CSNK1G2 (ENSG00000133275), CSNK1D (ENSG00000141551), TTBK1 (ENSG00000146216), CSNK1G3 (ENSG00000151292), CSNK1G1 (ENSG00000169118), CSNK1A1L (ENSG00000180138)

Protein

Protein identifiers

Casein kinase I isoform epsilon — P49674 (reviewed: P49674)

All UniProt accessions (11): A0A669KBC0, B0QY34, B0QY35, B0QY36, P49674, H0Y5S9, H0Y645, H0Y682, H7C0Y5, H7C3J2, Q5U045

UniProt curated annotations — full annotation on UniProt →

Function. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. Participates in Wnt signaling. Phosphorylates DVL1. Phosphorylates DVL2. Phosphorylates NEDD9/HEF1. Central component of the circadian clock. In balance with PP1, determines the circadian period length, through the regulation of the speed and rhythmicity of PER1 and PER2 phosphorylation. Controls PER1 and PER2 nuclear transport and degradation. Inhibits cytokine-induced granuloytic differentiation.

Subunit / interactions. Monomer. Component of the circadian core oscillator, which includes the CRY proteins, CLOCK, or NPAS2, ARTNL/BMAL1 or ARTNL2/BMAL2, CSNK1D and/or CSNK1E, TIMELESS and the PER proteins. Interacts with PER1. Interacts with ANKRD6. Interacts with DBNDD2. Interacts with LRP5 and LRP6. Interacts with SOCS3. Interacts with SNAI1 (via zinc fingers). Interacts with DDX3X; this interaction greatly enhances CSNK1E affinity for ATP and DVL2 phosphorylation, but inhibits DDX3X ATPase/helicase activity. In the presence of RNA, the interaction is decreased. Interacts with FAM83A, FAM83B, FAM83E and FAM83H (via DUF1669).

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in all tissues examined, including brain, heart, lung, liver, pancreas, kidney, placenta and skeletal muscle. Expressed in monocytes and lymphocytes but not in granulocytes.

Post-translational modifications. Autophosphorylated. Partially dephosphorylated by PPP5C. May be dephosphorylated by PP1.

Activity regulation. Phosphorylation leads to a decrease of the catalytic activity.

Induction. Down-regulated during granulocytic differentiation.

Similarity. Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. Casein kinase I subfamily.

RefSeq proteins (2): NP_001885, NP_689407* (*=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
IPR050235	CK1_Ser-Thr_kinase-like	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• 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 (48 total): helix 13, modified residue 8, turn 8, strand 8, sequence variant 2, compositionally biased region 2, binding site 2, chain 1, domain 1, mutagenesis site 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
4HNI	X-RAY DIFFRACTION	2.74
4HOK	X-RAY DIFFRACTION	2.77

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49674-F1	80.37	0.66

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): 128 (proton acceptor)

Ligand- & substrate-binding residues (2): 15–23; 38

Post-translational modifications (8): 362, 363, 382, 389, 405, 408, 343, 354

Mutagenesis-validated functional residues (1):

Position	Phenotype
38	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

28 pathways

ID	Pathway
R-HSA-201688	WNT mediated activation of DVL
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-5620912	Anchoring of the basal body to the plasma membrane
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A
R-HSA-8854518	AURKA Activation by TPX2
R-HSA-9931521	The CRY:PER:kinase complex represses transactivation by the BMAL:CLOCK (ARNTL:CLOCK) complex
R-HSA-9931530	Phosphorylation and nuclear translocation of the CRY:PER:kinase complex
R-HSA-162582	Signal Transduction
R-HSA-1640170	Cell Cycle
R-HSA-1852241	Organelle biogenesis and maintenance
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-380287	Centrosome maturation
R-HSA-400253
R-HSA-453274	Mitotic G2-G2/M phases
R-HSA-5617833	Cilium Assembly
R-HSA-68877	Mitotic Prometaphase
R-HSA-68886	M Phase
R-HSA-69275	G2/M Transition
R-HSA-69278	Cell Cycle, Mitotic
R-HSA-72312	rRNA processing
R-HSA-8868773	rRNA processing in the nucleus and cytosol
R-HSA-8953854	Metabolism of RNA

MSigDB gene sets: 331 (showing top): GOBP_CIRCADIAN_RHYTHM, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, YAGI_AML_WITH_INV_16_TRANSLOCATION, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_REGULATION_OF_NON_CANONICAL_WNT_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_CIRCADIAN_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, KAUFFMANN_DNA_REPAIR_GENES, CEBPB_01, GOBP_NEGATIVE_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (21): DNA repair (GO:0006281), protein phosphorylation (GO:0006468), endocytosis (GO:0006897), signal transduction (GO:0007165), intracellular protein localization (GO:0008104), negative regulation of Wnt signaling pathway (GO:0030178), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), regulation of protein localization (GO:0032880), circadian regulation of gene expression (GO:0032922), non-canonical Wnt signaling pathway (GO:0035567), regulation of circadian rhythm (GO:0042752), circadian behavior (GO:0048512), negative regulation of small GTPase mediated signal transduction (GO:0051058), canonical Wnt signaling pathway (GO:0060070), positive regulation of canonical Wnt signaling pathway (GO:0090263), positive regulation of amyloid-beta formation (GO:1902004), cellular response to nerve growth factor stimulus (GO:1990090), positive regulation of non-canonical Wnt signaling pathway (GO:2000052), regulation of Wnt signaling pathway (GO:0030111), positive regulation of Wnt signaling pathway (GO:0030177), rhythmic process (GO:0048511)

GO Molecular Function (9): RNA binding (GO:0003723), protein kinase activity (GO:0004672), protein serine/threonine kinase activity (GO:0004674), 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 (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), growth cone (GO:0030426), neuronal cell body (GO:0043025), ribonucleoprotein complex (GO:1990904), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
G2/M Transition	3
Centrosome maturation	2
Circadian clock	2
TCF dependent signaling in response to WNT	1
Loss of proteins required for interphase microtubule organization from the centrosome	1
Mitotic Prometaphase	1
Assembly of the 9+0 primary cilium	1
rRNA processing in the nucleus and cytosol	1
p53-Independent G1/S DNA Damage Checkpoint	1
Signal Transduction	1
Signaling by WNT	1
Cell Cycle, Mitotic	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
Wnt signaling pathway	5
cellular anatomical structure	4
circadian rhythm	3
regulation of Wnt signaling pathway	2
positive regulation of Wnt signaling pathway	2
protein kinase activity	2
DNA metabolic process	1
DNA damage response	1
phosphorylation	1
protein modification process	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
macromolecule localization	1
negative regulation of signal transduction	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
intracellular protein localization	1
regulation of localization	1
regulation of gene expression	1
regulation of biological process	1
rhythmic behavior	1
small GTPase-mediated signal transduction	1
regulation of small GTPase mediated signal transduction	1
negative regulation of intracellular signal transduction	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
amyloid-beta formation	1
regulation of amyloid-beta formation	1
positive regulation of amyloid precursor protein catabolic process	1
cellular response to growth factor stimulus	1
response to nerve growth factor	1

Protein interactions and networks

STRING

1628 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSNK1E	PER2	O15055	984
CSNK1E	CRY2	Q49AN0	961
CSNK1E	DDX3X	O00571	943
CSNK1E	CRY1	Q16526	938
CSNK1E	BMAL1	O00327	927
CSNK1E	GSK3B	P49841	890
CSNK1E	CLOCK	O15516	887
CSNK1E	NPAS2	Q99743	881
CSNK1E	PER3	P56645	881
CSNK1E	ANKRD6	Q9Y2G4	850
CSNK1E	AXIN1	O15169	845
CSNK1E	TIMELESS	Q9UNS1	832
CSNK1E	BHLHE40	O14503	830
CSNK1E	NR1D1	P20393	825
CSNK1E	RORA	P35397	804

IntAct

267 interactions, top by confidence:

A	B	Type	Score
FAM83H	CSNK1A1	psi-mi:“MI:0914”(association)	0.920
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
CSNK1E	MCC	psi-mi:“MI:0914”(association)	0.890
CSNK1E	PER2	psi-mi:“MI:0217”(phosphorylation reaction)	0.850
CSNK1E	PER2	psi-mi:“MI:0914”(association)	0.850
FAM83H	CSNK1E	psi-mi:“MI:0403”(colocalization)	0.850
PER2	CSNK1E	psi-mi:“MI:0915”(physical association)	0.850
CSNK1E	PER1	psi-mi:“MI:0914”(association)	0.840
DVL3	CSNK1E	psi-mi:“MI:0915”(physical association)	0.810
CSNK1E	DVL3	psi-mi:“MI:0915”(physical association)	0.810
FAM83B	CSNK1A1	psi-mi:“MI:0914”(association)	0.800
YWHAB	PIK3C2A	psi-mi:“MI:0914”(association)	0.800
CSNK1E	DVL2	psi-mi:“MI:0915”(physical association)	0.750
APC	CSNK1E	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
CSNK1E	FAM110C	psi-mi:“MI:0915”(physical association)	0.740
NCOA3	SPOP	psi-mi:“MI:0914”(association)	0.740
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (496): DVL3 (Two-hybrid), CSNK1E (Two-hybrid), CSNK1E (Reconstituted Complex), OCLN (Affinity Capture-Western), CSNK1E (Biochemical Activity), OCLN (Biochemical Activity), DEC1 (Two-hybrid), BHLHE41 (Two-hybrid), PER1 (Two-hybrid), PER2 (Two-hybrid), PPP1CC (Two-hybrid), PPP2R5E (Two-hybrid), RORC (Two-hybrid), CSNK1E (Two-hybrid), CSNK2B (Two-hybrid)

ESM2 similar proteins: A7E3X2, O74135, P29295, P35508, P40233, P40234, P40236, P42158, P48730, P49674, P51566, P78368, Q03141, Q06486, Q20471, Q39050, Q4R9A9, Q556Y4, Q5BP74, Q5PRD4, Q5R4V3, Q5RC72, Q5XF24, Q5ZJS0, Q5ZLL1, Q62761, Q62762, Q62763, Q6K9N1, Q6NRT0, Q6P3K7, Q6P647, Q7T2E3, Q8BTH8, Q8BVP5, Q8C4X2, Q8LPI7, Q8LPJ1, Q8VYK9, Q8WQ99

Diamond homologs: A7E3X2, B9VVJ6, O15726, O19175, O74135, O76324, O80888, P16912, P22517, P23291, P23292, P28327, P29295, P34516, P34633, P35507, P35508, P35509, P39962, P40230, P40233, P40234, P40235, P40236, P42158, P42168, P48729, P48730, P49615, P49674, P51166, P54367, P67827, P67828, P67829, P67962, P67963, P78368, P81123, P97633

SIGNOR signaling

60 interactions.

A	Effect	B	Mechanism
CSNK1E	“up-regulates activity”	APC	phosphorylation
N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide	down-regulates	CSNK1E	“chemical inhibition”
CSNK1E	up-regulates	TCF3	phosphorylation
CSNK1E	up-regulates	ROR2	phosphorylation
CSNK1E	down-regulates	LEF1	phosphorylation
CSNK1E	down-regulates	PER1	phosphorylation
CSNK1E	up-regulates	LRP6	phosphorylation
CSNK1E	up-regulates	DVL2	phosphorylation
CSNK1E	down-regulates	YAP1	phosphorylation
CSNK1E	down-regulates	EIF4EBP1	phosphorylation
CSNK1E	“up-regulates activity”	DVL1	phosphorylation
CSNK1E	up-regulates	GSK3B/Axin/APC	phosphorylation
CSNK1E	down-regulates	WWTR1	phosphorylation
CSNK1E	“down-regulates activity”	CTNNB1	phosphorylation
CSNK1E	down-regulates	CTNND1	phosphorylation
CSNK1E	“up-regulates activity”	BID	phosphorylation
CSNK1E	“down-regulates activity”	CSNK1E	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 196 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
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	9	49.6×	2e-11
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	8	44.0×	7e-10
Activation of BAD and translocation to mitochondria	7	43.7×	1e-08
Activation of BH3-only proteins	7	28.5×	3e-07
RHO GTPases activate PKNs	8	20.8×	3e-07
Intrinsic Pathway for Apoptosis	7	16.8×	1e-05
Disassembly of the destruction complex and recruitment of AXIN to the membrane	5	14.6×	6e-04
FOXO-mediated transcription	5	13.8×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
intracellular protein localization	10	6.3×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	31
Likely benign	0
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
590290	NM_152221.3(CSNK1E):c.885+1G>A	Pathogenic

SpliceAI

2318 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38293329:G:C	acceptor_gain	1.0000
22:38294245:TTGC:T	acceptor_gain	1.0000
22:38294246:TGC:T	acceptor_gain	1.0000
22:38294249:C:CC	acceptor_gain	1.0000
22:38294249:CT:C	acceptor_loss	1.0000
22:38294332:C:A	donor_gain	1.0000
22:38294337:CTCA:C	donor_loss	1.0000
22:38294338:TCA:T	donor_loss	1.0000
22:38294339:CA:C	donor_loss	1.0000
22:38294340:A:AC	donor_gain	1.0000
22:38294340:ACCAG:A	donor_gain	1.0000
22:38294341:C:CC	donor_gain	1.0000
22:38294341:CCAG:C	donor_gain	1.0000
22:38294341:CCAGC:C	donor_gain	1.0000
22:38294530:GCACC:G	acceptor_gain	1.0000
22:38294531:CACC:C	acceptor_gain	1.0000
22:38294531:CACCC:C	acceptor_gain	1.0000
22:38294532:ACC:A	acceptor_gain	1.0000
22:38294532:ACCCT:A	acceptor_gain	1.0000
22:38294533:CC:C	acceptor_gain	1.0000
22:38294533:CCC:C	acceptor_gain	1.0000
22:38294533:CCCT:C	acceptor_gain	1.0000
22:38294534:CC:C	acceptor_gain	1.0000
22:38294535:C:CC	acceptor_gain	1.0000
22:38294535:C:T	acceptor_gain	1.0000
22:38294538:C:CT	acceptor_gain	1.0000
22:38294539:A:T	acceptor_gain	1.0000
22:38294543:A:AC	acceptor_gain	1.0000
22:38294543:A:C	acceptor_gain	1.0000
22:38294546:C:CT	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000114570 (22:38317553 CA>C), RS1000213875 (22:38295400 G>A,T), RS1000260491 (22:38295486 C>T), RS1000311407 (22:38295820 C>A), RS1000466324 (22:38303930 C>G,T), RS1000713482 (22:38306485 C>A,T), RS1000826015 (22:38300962 A>G,T), RS1000937690 (22:38308644 T>C), RS1001099842 (22:38318979 T>C), RS1001534085 (22:38296154 C>T), RS1001550630 (22:38311448 G>A), RS1001592791 (22:38306393 C>CGTTTTTAG), RS1001646613 (22:38316706 G>A,C), RS1001698071 (22:38290587 G>A,T), RS1001892290 (22:38307719 C>G)

Disease associations

OMIM: gene MIM:600863 | disease phenotypes: MIM:308350

GenCC curated gene-disease

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Limited	Autosomal dominant

Mondo (4): cerebellar ataxia (MONDO:0000437), cardiac rhythm disease (MONDO:0007263), developmental and epileptic encephalopathy, 1 (MONDO:0010632), genetic developmental and epileptic encephalopathy (MONDO:0100062)

Orphanet (1): Rare ataxia (Orphanet:102002)

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST009677_1	Keratoconus	7.000000e-07
GCST011383_6	Mastocytosis	2.000000e-07

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002524	Cerebellar Ataxia	C10.228.140.252.190; C10.597.350.090.500; C23.888.592.350.090.200

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (5): CHEMBL2111458 (PROTEIN FAMILY), CHEMBL3038494 (PROTEIN COMPLEX), CHEMBL3883308 (PROTEIN-PROTEIN INTERACTION), CHEMBL4937 (SINGLE PROTEIN), CHEMBL6195527 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

37 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 447,660 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL180022	NERATINIB	4	9,404
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3948730	UMBRALISIB	4	2,833
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL939	GEFITINIB	4	117,814
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL31965	CANERTINIB	3	8,083
CHEMBL3544983	TESEVATINIB	3	2,819
CHEMBL491473	CEDIRANIB	3	9,098
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1090089	PAMAPIMOD	2	428
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1614713	CC-401	2	389
CHEMBL1721885	SU-014813	2	363
CHEMBL230011	TG100-115	2
CHEMBL2364611	GALUNISERTIB	2
CHEMBL253969	OSI-632	2
CHEMBL3545396	BMS-690514	2
CHEMBL363648	TAK-715	2
CHEMBL513909	BI-2536	2
CHEMBL521851	PICTILISIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL607707	PELITINIB	2
CHEMBL269538	HARMINE	1

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1534891	Toxicity	3	heroin	Heroin Dependence

PharmGKB variants

4 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs135745	CSNK1E		0.00	0
rs135757	CSNK1E		0.00	0
rs1534891	CSNK1E	3	0.00	1	heroin
rs6001093	CSNK1E		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Casein kinase 1 (CK1) family

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
PF-670462	Inhibition	8.11	pIC50
PF-4800567	Inhibition	7.49	pIC50
SR-4133	Inhibition	7.24	pIC50
IC261	Inhibition	6.0	pIC50
umbralisib	Inhibition	5.22	pEC50

Binding affinities (BindingDB)

874 measured of 1219 human assays (1220 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
N-(6-(4-(4-fluorophenyl)-1- (1-(2-hydroxyethyl)piperidin- 4-yl)-1H-imidazol-5-yl)imidazo [1,2-b]pyridazin-2-yl)- 4-methyl-2-(pyridin-3-yl) thiazole-5-carboxamide	IC50	0.034 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4- fluorophenyl)-1-(1- (2-hydroxyethyl)azetidin- 3-yl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin- 2-yl)isonicotinamide	IC50	0.034 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)-4-methyl-2-(pyridin-3-yl)thiazole-5-carboxamide	IC50	0.06 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1-(piperidin-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)isonicotinamide	IC50	0.064 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(2-aminoacetyl)piperidin-4- yl)-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.085 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(2-amino-2- oxoethyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b] pyridazin-2-yl)-4- methyl-2-(pyridin-3-yl) thiazole-5- carboxamide	IC50	0.091 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)- 1-(1-(2-hydroxyethyl) piperidin-4-yl)-1H-imidazol- 5-yl)imidazo[1,2-b]pyridazin- 2-yl)-4-methyl-2-(pyridin-4-yl) thiazole-5-carboxamide	IC50	0.096 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(2-(4-fluorophenyl) imidazo[1,2-a]pyridin-3-yl) imidazo[1,2-b]pyridazin-2-yl)- 2-pivalamidoisonicotinamide	IC50	0.096 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-[6-[3-(4-fluorophenyl)-5-[4-(2-hydroxyethyl)piperazin-1-yl]-1-methylpyrazol-4-yl]imidazo[1,2-b]pyridazin-2-yl]pyridine-4-carboxamide	IC50	0.1 nM	US-9475817: Pyrazole substituted imidazopyrazines as casein kinase 1 d/e inhibitors
N-[6-[5-[4-(2-aminoacetyl)piperazin-1-yl]-3-(4-fluorophenyl)-1-methylpyrazol-4-yl]imidazo[1,2-b]pyridazin-2-yl]-2-fluoropyridine-4-carboxamide	IC50	0.1 nM	US-9475817: Pyrazole substituted imidazopyrazines as casein kinase 1 d/e inhibitors
2-Fluoro-N-(6-(2-(4-fluorophenyl)-7-pivaloyl- 5,6,7,8-tetrahydroimidazo[1,2-a]pyrazin-3- yl)imidazo[1,2-b]pyridazin-2- yl)isonicotinamide	IC50	0.1 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-((1,3-dimethyl-1H-pyrazol-4- yl)methyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.101 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1- (2-morpholinoethyl)-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)-3- (pyridin-3-yl)benzamide	IC50	0.104 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-chlorophenyl)-1-(2- fluoroethyl)-2-methyl-1H-imidazol- 5-yl)imidazo[1,2-b]pyridazin-2-yl)- 2-fluoroisonicotinamide	IC50	0.109 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1- (2-morpholinoethyl)-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)-2- morpholinoisonicotinamide	IC50	0.11 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-Fluoro-N-(6-(1-(2-fluoroethyl)-4-(4-fluorophenyl)-2-methyl-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)isonicotinamide	IC50	0.11 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-(dimethylamino)-N-(6-(2-(4- fluorophenyl)imidazo[1,2-a] pyridin-3-yl)imidazo[1,2-b] pyridazin-2-yl) isonicotinamide	IC50	0.111 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
(S)-2-fluoro-N-(6-(4-(4- fluorophenyl)-2-methyl-1- (1-(3,3,3-trifluoro-2- hydroxypropyl)piperidin-4- yl)-1H-imidazol-5-yl)imidazo [1,2-b]pyridazin-2- yl)isonicotinamide	IC50	0.112 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(3,3- difluorocyclobutanecarbonyl)piperidin- 4-yl)-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.116 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-chlorophenyl)-2-methyl- 1-(2,2,2-trifluoroethyl)-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)-2-fluoroisonicotin- amide	IC50	0.126 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1- (2-hydroxyacetyl)piperidin-4-yl)-1H- imidazol-5-yl)imidazo[1,2-6]pyridazin- 2-yl)isonicotinamide	IC50	0.128 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1 isonicotinoylpiperidin-4-yl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazin- 2-yl)isonicotinamide	IC50	0.13 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1- (2-methoxyethyl)piperidin-4-yl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazin- 2-yl)isonicotinamide	IC50	0.136 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
3,3,3-trifluoropropyl 4-(5-(2-(2- fluoroisonicotinamido)imidazo[1,2- b]pyridazin-6-yl)-4-(4-fluorophenyl)- 1H-imidazol-1-yl)piperidine-1- carboxylate	IC50	0.142 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(3- chloropropanoyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.143 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(2-amino-2- oxoethyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2,6- difluoroisonicotinamide	IC50	0.146 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)- 1-(2-(1H-pyrazol-4-yl)ethyl-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)isonicotinamide	IC50	0.147 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
6-fluoro-N-(6-(4-(4-fluoro- phenyl)-1,2-dimethyl-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)nicotinamide	IC50	0.152 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1-(1-(3,3,3-trifluoropropyl)piperidin-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)thiazole-5-carboxamide	IC50	0.159 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1- ((5-methylisoxazol-3- yl)methyl)piperidin-4-yl)-1H-imidazol- 5-yl)imidazo[1,2-b]pyridazin-2- yl)isonicotinamide	IC50	0.165 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1-(furan-3- ylmethyl)-1H-imidazol-5-yl)imidazo[1,2- b]pyridazin-2-yl)pivalamide	IC50	0.169 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-((1H-pyrazol-5- yl)methyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.17 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
oxetan-3-yl 4-[4-(4-fluorophenyl)-5-[2-[(2-fluoropyridine-4-carbonyl)amino]imidazo[1,2-b]pyridazin-6-yl]imidazol-1-yl]piperidine-1-carboxylate	IC50	0.171 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(1- cyanocyclopropanecarbonyl)piperidin- 4-yl)-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.172 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1-(1-(isoxazole-3-carbonyl)piperidin-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)thiazole-5-carboxamide	IC50	0.173 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1- (1-(3,3,3-trifluoropropanoyl) piperidin-4-yl)-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)thiazole- 5-carboxamide	IC50	0.175 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1- (2-hydroxy-2-methylpropanoyl) piperidin-4-yl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2- yl)isonicotinamide	IC50	0.178 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
methyl 4-[4-(4-fluorophenyl)-5-[2-[(2-fluoropyridine-4-carbonyl)amino]imidazo[1,2-b]pyridazin-6-yl]imidazol-1-yl]piperidine-1-carboxylate	IC50	0.179 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1- (2-morpholinoethyl)piperidin-4-yl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazin- 2-yl)isonicotinamide	IC50	0.183 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(1H-imidazole-4- carbonyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo(1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.183 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluorophenyl)-1-(1- (2-morpholinoacetyl)piperidin-4-yl)-1H- imidazol-5-yl)imidazo[1,2-b]pyridazin- 2-yl)isonicotinamide	IC50	0.186 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(4-(4-fluoro-3- methylphenyl)-1-(2-fluoroethyl)- 2-methyl-1H-imidazol-5-yl) imidazo[1,2-b]pyridazin-2-yl) isonicotinamide	IC50	0.186 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1,2- dimethyl-1H-imidazol-5-yl) imidazo[1,2-b]pyridazin-2- yl)isoquinoline-6- carboxamide	IC50	0.187 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
2-fluoro-N-(6-(1-(1-(4- fluorobenzoyl)piperidin-4-yl)-4-(4- fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2- yl)isonicotinamide	IC50	0.191 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(4-(4-fluorophenyl)-1- (2-morpholinoethyl)-1H- imidazol-5-yl)imidazo[1,2-b] pyridazin-2-yl)quinoline- 4-carboxamide	IC50	0.192 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1- (cyclobutanecarbonyl)piperidin-4-yl)-4- (4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.193 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
(S)—N-(6-(4-(4-fluorophenyl)-1-(1-(3,3,3-trifluoro-2-hydroxypropyl)piperidin-4-yl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)thiazole-5-carboxamide	IC50	0.194 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
(S)-N-(6-(4-(4-fluorophenyl)-1-(1-(3,3,3- trifluoro-2-hydroxypropyl)piperidin-4-yl)- 1H-imidazol-5-yl)imidazo[1,2- b]pyridazin-2-yl)isonicotinamide	IC50	0.195 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(2-cyanoethyl)piperidin-4-yl)-4-(4-fluorophenyl)-1H-imidazol-5-yl)imidazo[1,2-b]pyridazin-2-yl)-2-fluoroisonicotinamide	IC50	0.197 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors
N-(6-(1-(1-(2-cyanoacetyl)piperidin-4- yl)-4-(4-fluorophenyl)-1H-imidazol-5- yl)imidazo[1,2-b]pyridazin-2-yl)-2- fluoroisonicotinamide	IC50	0.198 nM	US-9556179: Substituted imidazoles as casein kinase 1 D/E inhibitors

ChEMBL bioactivities

1268 potent at pChembl≥5 of 1290 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.02	IC50	0.095	nM	CHEMBL5914602
10.02	IC50	0.096	nM	CHEMBL5948403
9.89	IC50	0.128	nM	CHEMBL5757040
9.77	IC50	0.17	nM	CHEMBL5819750
9.74	IC50	0.183	nM	CHEMBL6017462
9.74	IC50	0.182	nM	CHEMBL5885676
9.70	IC50	0.2	nM	CHEMBL3962177
9.65	IC50	0.225	nM	CHEMBL5742519
9.65	IC50	0.222	nM	CHEMBL5884113
9.63	IC50	0.233	nM	CHEMBL5883463
9.59	IC50	0.256	nM	CHEMBL5777892
9.55	IC50	0.283	nM	CHEMBL5827750
9.53	IC50	0.298	nM	CHEMBL5842545
9.53	IC50	0.297	nM	CHEMBL5852327
9.52	IC50	0.3	nM	CHEMBL3978116
9.52	IC50	0.3	nM	CHEMBL4108038
9.52	IC50	0.305	nM	CHEMBL5854456
9.45	IC50	0.356	nM	CHEMBL5819750
9.43	IC50	0.372	nM	CHEMBL5815025
9.41	IC50	0.391	nM	CHEMBL6050808
9.40	IC50	0.4	nM	CHEMBL3912884
9.38	IC50	0.412	nM	CHEMBL5869184
9.37	IC50	0.424	nM	CHEMBL5996818
9.34	IC50	0.457	nM	CHEMBL5890047
9.34	IC50	0.461	nM	CHEMBL5929543
9.31	IC50	0.493	nM	CHEMBL5805800
9.31	IC50	0.484	nM	CHEMBL5940368
9.26	IC50	0.545	nM	CHEMBL5839004
9.25	IC50	0.559	nM	CHEMBL5928816
9.25	IC50	0.564	nM	CHEMBL5895694
9.22	IC50	0.6	nM	CHEMBL3944464
9.22	IC50	0.599	nM	CHEMBL5863703
9.22	IC50	0.608	nM	CHEMBL6045004
9.21	IC50	0.61	nM	CHEMBL6013357
9.18	IC50	0.654	nM	CHEMBL5806896
9.18	IC50	0.656	nM	CHEMBL5767137
9.17	IC50	0.681	nM	CHEMBL5907961
9.17	IC50	0.675	nM	CHEMBL5980138
9.17	IC50	0.676	nM	CHEMBL5876214
9.17	IC50	0.676	nM	CHEMBL5960479
9.16	IC50	0.687	nM	CHEMBL6053955
9.14	IC50	0.719	nM	CHEMBL5891223
9.13	IC50	0.743	nM	CHEMBL5758970
9.12	IC50	0.76	nM	CHEMBL5886294
9.12	IC50	0.768	nM	CHEMBL5777874
9.10	IC50	0.8	nM	CHEMBL3981677
9.10	IC50	0.798	nM	CHEMBL5929823
9.10	IC50	0.796	nM	CHEMBL5761303
9.10	IC50	0.8	nM	CHEMBL5867202
9.09	IC50	0.811	nM	CHEMBL5748483

PubChem BioAssay actives

590 with measured affinity, of 2552 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-fluorophenyl)-3-pyridin-4-yl-6-(4-pyrrolidin-1-ylpiperidin-1-yl)imidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0010	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148159: Binding affinity to human CSNK1E incubated for 45 mins by Kinobead based pull down assay	kd	0.0035	uM
5-(3-chloroanilino)benzo[c][2,6]naphthyridine-8-carboxylic acid	1831537: Inhibition of CK1 (unknown origin)	ic50	0.0040	uM
4-N-[5-chloro-4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]pyrimidin-2-yl]cyclohexane-1,4-diamine	1868083: Inhibition of CSNK1E (unknown origin)	ic50	0.0044	uM
6-(3,3-dimethylpiperazin-1-yl)-2-phenyl-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0046	uM
3-[(3-chlorophenoxy)methyl]-1-(oxan-4-yl)pyrazolo[3,4-d]pyrimidin-4-amine	2197741: Inhibition of recombinant human full-length N-terminal GST-tagged CK1epsilon expressed in baculovirus infected Sf9 insect cells using casein as substrate measured after 60 mins by ADP-glo kinase assay	ec50	0.0074	uM
(7S)-2-(3,5-difluoro-4-hydroxyanilino)-7,8-dimethyl-5-[(3-methyl-1,2-oxazol-5-yl)methyl]-7H-pteridin-6-one	2077285: Inhibition of human CK1 epsilon assessed as inhibition constant by Cheng-Prusoff equation analysis	ki	0.0075	uM
4-[3-cyclohexyl-5-(4-fluorophenyl)imidazol-4-yl]pyrimidin-2-amine	1733440: Inhibition of full-length human CK1epsilon expressed in Escherichia coli BL21-CodonPlus(DE3)-RIL competent cells using PLSRTLpSVASLPGL as substrate incubated for 3 hrs in presence of ATP by Kinase-Glo luminescence assay	ic50	0.0077	uM
2-(3,5-dimethylphenyl)-6-(3,3-dimethylpiperazin-1-yl)-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0086	uM
(12S)-22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,4’-piperidine]-12-ol	2104188: Inhibition of N-terminal GST-tagged human CSNK1E (1 to 348 residues) expressed in baculovirus infected Sf21 insect cells preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0116	uM
Sunitinib	435650: Binding constant for full-length CSNK1E	kd	0.0130	uM
6-[(3S)-3-methylpiperazin-1-yl]-2-phenyl-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0137	uM
22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,3’-azetidine]	2104188: Inhibition of N-terminal GST-tagged human CSNK1E (1 to 348 residues) expressed in baculovirus infected Sf21 insect cells preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0140	uM
2-(4-fluorophenyl)-6-[(3S)-3-methylpiperazin-1-yl]-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0142	uM
6-(3,3-dimethylpiperazin-1-yl)-2-(4-fluorophenyl)-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0146	uM
6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-(4-fluorophenyl)-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0157	uM
N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-9-(2,5-difluorophenyl)-2-morpholin-4-ylpurin-6-amine	1373028: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay	ic50	0.0160	uM
4-[5-(4-fluorophenyl)-3-[1-(1,2-oxazol-3-ylmethyl)piperidin-4-yl]imidazol-4-yl]pyrimidin-2-amine	1733443: Inhibition of wild-type human CK1epsilon using PLSRTLpSVASLPGL as substrate incubated for 70 mins in presence of ATP by Kinase-Glo luminescence assay	ic50	0.0170	uM
2-phenyl-3-pyridin-4-yl-6-(4-pyrrolidin-1-ylpiperidin-1-yl)imidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0260	uM
22-propan-2-ylspiro[10-oxa-2,18,20,24,25,26-hexazatetracyclo[17.6.1.04,9.021,25]hexacosa-1(26),4,6,8,19,21,23-heptaene-16,4’-piperidine]	2104188: Inhibition of N-terminal GST-tagged human CSNK1E (1 to 348 residues) expressed in baculovirus infected Sf21 insect cells preincubated for 10 mins followed by substrate addition and measured after 60 mins in presence of ATP by ADP-Glo reagent based luminescence microtiter plate reader analysis	ki	0.0266	uM
9-[3-(4-fluorophenyl)-1-methylpyrazol-4-yl]-2,3,4,5-tetrahydropyrido[2,3-f][1,4]oxazepine	767015: Inhibition of CK1 epsilon (unknown origin) using PLSRTLpSVASLPGL as substrate after 85 mins by microplate reader analysis	ic50	0.0270	uM
3-[4-[3-(4-fluorophenyl)-1-methylpyrazol-4-yl]-2-pyridinyl]morpholine	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0280	uM
4-[2-[6-[(4,5-difluoro-1H-benzimidazol-2-yl)methylamino]-2-morpholin-4-ylpurin-9-yl]ethyl]phenol	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0300	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624847: Binding constant for CSNK1E kinase domain	kd	0.0310	uM
N-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-2-[[2-(trifluoromethoxy)benzoyl]amino]-1,3-thiazole-4-carboxamide	1277308: Inhibition of recombinant human CK1epsilon using GST-p53 (1 to 64 residues) as substrate by SDS-PAGE based autoradiography	ic50	0.0326	uM
N-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-2-[[2-(trifluoromethoxy)benzoyl]amino]-1,3-oxazole-4-carboxamide	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0330	uM
(4Z)-4-(2-amino-5-oxo-1H-imidazol-4-ylidene)-2-bromo-1,5,6,7-tetrahydropyrrolo[2,3-c]azepin-8-one	1924344: Inhibition of CK1 (unknown origin)	ic50	0.0350	uM
9-(1-benzothiophen-2-yl)-N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-2-morpholin-4-ylpurin-6-amine	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0360	uM
2-[4-[1-[9-cyclopentyl-6-[(2,3-difluorophenyl)methylamino]purin-2-yl]piperidin-4-yl]piperidin-1-yl]ethanol	2141435: Inhibition of CK1epsilon (unknown origin)	ic50	0.0380	uM
4-[3-(4-hydroxyphenyl)-2H-pyrazolo[3,4-b]pyridin-5-yl]benzene-1,2-diol	1947677: Inhibition of recombinant human CK1epsilon expressed in Sf9 insect cells incubated for 60 mins in presence of ATP and [gamma33-P] ATP by radiometric scintillation counter analysis	ic50	0.0389	uM
2-(3,5-difluorophenyl)-6-(3,3-dimethylpiperazin-1-yl)-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0430	uM
[1-[6-[(4,5-difluoro-1H-benzimidazol-2-yl)methylamino]-9-(3-fluorophenyl)purin-2-yl]piperidin-4-yl]methanol	1373028: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay	ic50	0.0500	uM
9-(3-fluorophenyl)-N-[[5-(4-methylpiperazin-1-yl)-2-pyridinyl]methyl]-2-morpholin-4-ylpurin-6-amine	1373028: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay	ic50	0.0540	uM
2-methyl-6-piperazin-1-yl-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1934124: Inhibition of human CK1 epsilon incubated for 2 hrs by scintillation counter analysis	ic50	0.0570	uM
N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-2-morpholin-4-yl-9-naphthalen-2-ylpurin-6-amine	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0580	uM
(5Z)-5-(1,3-benzothiazol-6-ylmethylidene)-2-[(3,5,7-trifluoro-1-adamantyl)imino]imidazolidin-4-one	2010384: Inhibition of human CK1 epsilon using casein and [gamma33P]ATP as substrate incubated for 60 mins by radiometric 33PanQinase assay	ic50	0.0620	uM
1-[4-[3-(4-fluorophenyl)-1-methylpyrazol-4-yl]-2-pyridinyl]-N-methylmethanamine	767015: Inhibition of CK1 epsilon (unknown origin) using PLSRTLpSVASLPGL as substrate after 85 mins by microplate reader analysis	ic50	0.0672	uM
6-(2,5-diazabicyclo[2.2.1]heptan-2-yl)-2-phenyl-3-pyridin-4-ylimidazo[1,2-b]pyridazine	1531988: Inhibition of human CK1 epsilon using casein as substrate after 2 hrs in presence of [33P]-ATP by scintillation counting analysis	ic50	0.0700	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	435650: Binding constant for full-length CSNK1E	kd	0.0730	uM
(E)-3-(2,4-dimethoxyphenyl)-N-[4-[5-(4-fluorophenyl)-2-methylsulfanyl-1H-imidazol-4-yl]-2-pyridinyl]prop-2-enamide	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0730	uM
N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-9-(2,3-difluorophenyl)-2-morpholin-4-ylpurin-6-amine	1373028: Inhibition of recombinant human full length N-terminal GST-tagged CK1epsilon expressed in baculovirus in Sf9 insect cells using ULight-Topo-IIa(Thr1342) peptide as substrate after 10 mins by TR-FRET assay	ic50	0.0800	uM
[4-[3-(4-fluorophenyl)-1-methylpyrazol-4-yl]-2-pyridinyl]methanol	767015: Inhibition of CK1 epsilon (unknown origin) using PLSRTLpSVASLPGL as substrate after 85 mins by microplate reader analysis	ic50	0.0816	uM
N-[(4,5-difluoro-1H-benzimidazol-2-yl)methyl]-9-[2-(furan-3-yl)ethyl]-2-morpholin-4-ylpurin-6-amine	1989848: Inhibition of CK1epsilon (unknown origin)	ic50	0.0880	uM
2-(5-fluoro-2-pyridinyl)-6,6-dimethyl-3-(1H-pyrazolo[3,4-b]pyridin-4-yl)-4,7-dihydropyrazolo[5,1-c][1,4]oxazine	1985802: Inhibition of CK1 epsilon (unknown origin)	ic50	0.0930	uM
(E)-N-[4-(3-chloro-4-fluoroanilino)-3-cyano-7-ethoxyquinolin-6-yl]-4-(dimethylamino)but-2-enamide	256644: Average Binding Constant for CSNK1E; NA=Not Active at 10 uM	kd	0.0970	uM
3-(1H-indazol-5-yl)-N-propylimidazo[1,2-b]pyridazin-6-amine	1909338: Inhibition of human recombinant CK1 epsilon expressed in baculovirus in sf9 insect cells using RRKHAAIGSpAYSITA as substrate in presence of ATP measured after 30 mins by ADP-Glo assay	ic50	0.0990	uM
4-[5-(2-chloro-6-fluoroanilino)-6-methylpyrazolo[3,4-b]pyridin-1-yl]-N-(oxetan-3-yl)thiophene-2-carboxamide	1780554: Inhibition of human CK1E using KRRRAL[pS]VASLPGL as substrate by [gamma-33P]-ATP assay	ic50	0.1000	uM
4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine	435650: Binding constant for full-length CSNK1E	kd	0.1000	uM
(1E)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one	1722617: Binding affinity to CSNK1E (unknown origin)	kd	0.1000	uM
4-[4-(4-fluorophenyl)-2-(4-methylsulfonylphenyl)-1H-imidazol-5-yl]pyridine	1899316: Binding affinity to CK1epsilon (unknown origin)	kd	0.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression	4
bisphenol A	affects methylation, decreases expression	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
pirinixic acid	increases activity, affects binding, decreases expression	1
arsenite	affects localization, affects binding, increases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, increases methylation	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
isobutyl alcohol	increases expression, affects cotreatment, increases abundance	1
K 7174	increases expression	1
IC 261	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	increases expression	1
ICG 001	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
3-(3-chlorophenoxymethyl)-1-(tetrahydropyran-4-yl)-1H-pyrazolo(3,4-d)pyrimidin-4-ylamine	affects binding, decreases activity, decreases phosphorylation	1
NSC668394	increases expression	1
Sunitinib	increases expression	1
Fulvestrant	increases methylation	1
Vorinostat	decreases expression	1
Amphetamine	affects response to substance, increases response to substance	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Benzene	decreases expression	1
Cadmium	affects expression	1
Caffeine	decreases phosphorylation	1
Cannabinoids	increases abundance, increases methylation	1
Copper	affects binding, increases expression	1
Disulfiram	increases expression, affects binding	1
Estradiol	affects expression	1

ChEMBL screening assays

420 unique, capped per target: 416 binding, 2 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1051274	Binding	Percent residual CK1 activity in the presence of 10uM inhibitor	Biochemical and three-dimensional-structural study of the specific inhibition of protein kinase CK2 by [5-oxo-5,6-dihydroindolo-(1,2-a)quinazolin-7-yl]acetic acid (IQA). — Biochem J
CHEMBL4606500	ADMET	Inhibition of recombinant human full-length His-tagged CKepsilon expressed in baculovirus expression system at 1 uM by Lanthascreen assay relative to control	Optimizing Pyrazolopyrimidine Inhibitors of Calcium Dependent Protein Kinase 1 for Treatment of Acute and Chronic Toxoplasmosis. — J Med Chem
CHEMBL5444983	Functional	Affinity Phenotypic Cellular interaction: (Western Blot assay (inhibition of CSNK1D/E-mediated phosphorylation of DVL3, analyzed by change in phosphorylation-dependent mobility shift)) EUB0001205a CSNK1E	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1PF	Abcam HeLa CSNK1E KO	Cancer cell line	Female
CVCL_SJ83	HAP1 CSNK1E (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT04107740	PHASE4	COMPLETED	C-Trelin Orally Disintegrated(OD) Tablet 5mg in Ataxia Due to Spinocerebellar Degeneration
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NCT00290056	PHASE4	UNKNOWN	Effect of Supplemental Intake of Omega-3 Polyunsaturated Fatty Acids on the Rate and Complexity of Spontaneously Occurring Ventricular and Supraventricular Arrhythmias in Patients With Implantable Cardioverter Defibrillator (ICD) - A Randomized Clinical Trial
NCT00313443	PHASE4	COMPLETED	Concentrations of Amiodarone in Fat Tissue During Chronic Treatment
NCT00457340	PHASE4	COMPLETED	Atorvastatin For The Reduction Of Ventricular Arrhythmias
NCT00507390	PHASE4	WITHDRAWN	Omega 3 Polyunsaturated Fatty Acid Supplements (PUFAs) and Microvolt T Wave Alternans (TWA) in Patients With Ventricular Arrhythmia
NCT00575523	PHASE4	COMPLETED	Atropine for Prevention of Dysrhythmias Caused by Percutaneous Ethanol Instillation for Hepatoma Therapy
NCT00579098	PHASE4	COMPLETED	The Use of Statins Following a Left Atrial Catheter Ablation Procedure to Prevent Atrial Fibrillation
NCT01613092	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01628666	PHASE4	COMPLETED	Prevention of Arrhythmia Device Infection Trial (PADIT)
NCT01717469	PHASE4	UNKNOWN	Safety and the Effects of Isolated Left Ventricular Pacing in Patients With Bradyarrhythmias
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NCT01991223	PHASE4	UNKNOWN	Dexmedetomidine for Catheter-related Bladder Discomfort
NCT02045173	PHASE4	COMPLETED	Automate Detection of Sleep Apnea by ApneascanTM
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NCT02565069	PHASE4	COMPLETED	Identification for the Treatment of Complex Arrhythmias
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NCT06908226	PHASE3	ENROLLING_BY_INVITATION	A Study to Investigate LP352 in Children and Adults With Developmental and Epileptic Encephalopathy (DEE)
NCT01970098	PHASE3	COMPLETED	A Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970111	PHASE3	COMPLETED	An Extension Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970124	PHASE3	COMPLETED	A Long-Term Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT01970137	PHASE3	COMPLETED	A 24-week Open-label Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT02889302	PHASE3	COMPLETED	An Additional Confirmatory Study of KPS-0373 in Patients With Spinocerebellar Degeneration (SCD)
NCT03408080	PHASE3	ACTIVE_NOT_RECRUITING	Open Pilot Trial of BHV-4157
NCT03701399	PHASE3	ACTIVE_NOT_RECRUITING	Troriluzole in Adult Participants With Spinocerebellar Ataxia
NCT03901638	PHASE3	TERMINATED	Tllsh2910 for Ataxia and Gut Microbiota Alteration in Patients of Multiple System Atrophy
NCT07040137	PHASE3	RECRUITING	Confirmatory Study 3 of KPS-0373 in Patients With Spinocerebellar Degeneration
NCT00000464	PHASE3	COMPLETED	Cardiac Arrest in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE)
NCT00000476	PHASE3	COMPLETED	Digitalis Investigation Group (DIG)