CSNK1A1

Summary

CSNK1A1 (casein kinase 1 alpha 1, HGNC:2451) is a protein-coding gene on chromosome 5q32, encoding Casein kinase I isoform alpha (P48729). Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates. It is a selective cancer dependency (DepMap: 79.5% of cell lines).

Enables protein serine/threonine kinase activity. Involved in several processes, including intermediate filament cytoskeleton organization; positive regulation of proteasomal ubiquitin-dependent protein catabolic process; and regulation of signal transduction. Located in cytoskeleton and nucleus. Part of beta-catenin destruction complex. Biomarker of Alzheimer’s disease and inclusion body myositis.

Source: NCBI Gene 1452 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 20 total
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 79.5% of screened cell lines
• MANE Select transcript: NM_001892

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2451
Approved symbol	CSNK1A1
Name	casein kinase 1 alpha 1
Location	5q32
Locus type	gene with protein product
Status	Approved
Aliases	CK1, CK1a, CK1alpha, CKIa, CKIalpha
Ensembl gene	ENSG00000113712
Ensembl biotype	protein_coding
OMIM	600505
Entrez	1452

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 10 protein_coding, 6 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000261798, ENST00000377843, ENST00000503350, ENST00000504676, ENST00000515435, ENST00000515748, ENST00000515768, ENST00000523203, ENST00000606299, ENST00000606719, ENST00000606826, ENST00000657001, ENST00000657462, ENST00000657706, ENST00000661952, ENST00000662268, ENST00000670598

RefSeq mRNA: 4 — MANE Select: NM_001892 NM_001025105, NM_001271741, NM_001271742, NM_001892

CCDS: CCDS47303, CCDS47304, CCDS64291

Canonical transcript exons

ENST00000377843 — 10 exons

Exon	Start	End
ENSE00000767015	149507027	149507133
ENSE00000767020	149509879	149509953
ENSE00000767021	149511794	149511872
ENSE00000767053	149520290	149520388
ENSE00000767067	149550075	149550181
ENSE00000972769	149513070	149513209
ENSE00001033077	149505447	149505595
ENSE00001962046	149492982	149496860
ENSE00003468869	149525045	149525171
ENSE00003885953	149550842	149551439

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.54.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.3460 / max 868.3864, expressed in 1825 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64127	39.9742	1820
64123	14.7425	1744
64128	7.0478	1771
64124	1.9497	904
64125	1.0946	632
64130	0.5697	321
64129	0.5164	289
64126	0.4512	237

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	98.54	gold quality
cortical plate	UBERON:0005343	98.41	gold quality
adrenal tissue	UBERON:0018303	98.36	gold quality
islet of Langerhans	UBERON:0000006	98.17	gold quality
gall bladder	UBERON:0002110	98.01	gold quality
smooth muscle tissue	UBERON:0001135	97.97	gold quality
ganglionic eminence	UBERON:0004023	97.97	gold quality
colonic epithelium	UBERON:0000397	97.91	gold quality
ventricular zone	UBERON:0003053	97.90	gold quality
nipple	UBERON:0002030	97.87	gold quality
calcaneal tendon	UBERON:0003701	97.70	gold quality
embryo	UBERON:0000922	97.69	gold quality
pylorus	UBERON:0001166	97.69	gold quality
esophagus mucosa	UBERON:0002469	97.58	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	97.48	gold quality
skin of abdomen	UBERON:0001416	97.46	gold quality
rectum	UBERON:0001052	97.45	gold quality
esophagus	UBERON:0001043	97.43	gold quality
pancreatic ductal cell	CL:0002079	97.39	gold quality
cauda epididymis	UBERON:0004360	97.35	gold quality
skin of leg	UBERON:0001511	97.27	gold quality
descending thoracic aorta	UBERON:0002345	97.25	gold quality
lower esophagus mucosa	UBERON:0035834	97.21	gold quality
lower esophagus	UBERON:0013473	97.20	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.20	gold quality
monocyte	CL:0000576	97.03	gold quality
right coronary artery	UBERON:0001625	96.87	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.84	gold quality
mononuclear cell	CL:0000842	96.83	gold quality
thoracic aorta	UBERON:0001515	96.81	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-MTAB-10596	no	1050.15
E-CURD-112	no	2.54
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, SOX17, SRY, TP53

miRNA regulators (miRDB)

108 targeting CSNK1A1, 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-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-6857-5P	99.87	65.32	985

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 79.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Biochemical and cellular characteristics of the four splice variants of protein kinase CK1alpha from zebrafish (Danio rerio)are presented. (PMID:12210746)
• CK1alpha can promote cell survival by interfering with RXR agonist-induced apoptosis (PMID:15131121)
• CK1alpha-mediated phosphorylation modulates the mRNA binding ability of hnRNP-C (PMID:15687492)
• NFAT1, a transcription factor connected with breast cancer metastasis, is activated by Wnt-5a through a Ca2+ signaling pathway in human breast epithelial cells which was simultaneously counteracted by a Wnt-5a-induced Yes/Cdc42 signaling pathway. (PMID:16880514)
• identification of the alpha isoform of casein kinase I as the cellular kinase important for the formation of hepatitis C virus (HCV) NS5A-p58; here we show the effects of this kinase on NS5A hyperphosphorylation and HCV replication (PMID:16943283)
• CK1alphaLS and hnRNP-C represent conserved components of a vertebrate-specific H(2)O(2)-responsive nuclear signaling pathway. (PMID:17626781)
• Studies suggest that CK1alpha is another kinase that regulates RIP1 function in NF-kappaB activation. (PMID:18067272)
• following DNA damage, PML facilitates Thr18 phosphorylation by recruiting p53 and CK1 into PML nuclear bodies, thereby protecting p53 from inhibition by Mdm2, leading to p53 activation. (PMID:18246126)
• Ser-155 and Ser-158 have important roles in the nucleocytoplasmic trafficking of OREBP/TonEBP and CK1 plays a major role in regulating this process (PMID:18411282)
• We show that the inhibition of CK1 activates RhoB and promotes RhoB dependent actin fiber formation and EGF-R level. (PMID:18590726)
• CK1 has a role as the Ser20 site kinase for p53 in DNA virus-infected cells (PMID:18669630)
• Phosphorylation of parkin by casein kinase I and cdk5 decreases parkin solubility, leading to its aggregation and inactivation. (PMID:19050041)
• ‘activated B-cell-like’ subtype of diffuse large B-cell lymphoma cells required CK1alpha for constitutive NF-kappaB activity, indicating that CK1alpha functions as a conditionally essential malignancy gene (PMID:19118383)
• Casein Kinase 1 phosphorylates serine 56 of yellow fever virus methyltransferase. (PMID:19185594)
• Data show that Wnt-5a stimulation of breast epithelial cells leads to increased cell-cell adhesion, and that Wnt-5a/casein kinase Ialpha (CKIalpha)-specific phosphorylation of beta-catenin leads to increased complex formation of beta-catenin/E-cadherin. (PMID:19244247)
• CK1alpha plays a central role in mediating MDM2 control of p53 and E2F-1 protein stability (PMID:19759023)
• Results suggest a role for mammalian and parasite casein kinase 1alpha in regulating IFNAR1 stability and type I IFN signaling. (PMID:19805514)
• Casein kinase 1 functions as both penultimate and ultimate kinase in regulating Cdc25A destruction. (PMID:20348946)
• Our results indicate that the nuclear form of CK1alpha in humans, CK1alphaLS, plays a critical role in vascular cell proliferation, cellular activation, and hydrogen peroxide-mediated mitogenic signal transduction. (PMID:20696773)
• The authors characterized the role of CKIalpha in the clock mechanism and found that CKIalpha-mediated phosphorylation stimulated degradation of a clock protein PER1, similar to the function of CKIdelta. (PMID:21179498)
• We showed that just four genes, G3BP2, SCARB2, CSNK1A1 and SPRR2B, can classify patients as presence of lymph node metastasis negative or positive, with 80.0% accuracy. (PMID:21985131)
• mTOR cooperates with CK1alpha and betaTrCP to generate an auto-amplification loop to promote its own full activation. (PMID:22017877)
• identified casein kinase 1alpha (CK1alpha) as a direct target of miR-155 control which enhanced beta-catenin signaling and cyclin D1 expression, promoting tumor cell growth (PMID:22350414)
• DNA damage activates p53 in part by disrupting CK1a-MDMX interaction and reducing MDMX-p53 binding affinity. (PMID:23028042)
• The substrate interacting residues in ck1alpha have been identified using the structural model of kinase - substrate peptide. The PKR interacting NS5A 1b residues have also been predicted. (PMID:23148689)
• Data indicate that protein S phosphorylation by casein kinase 1 (CK1) and casein kinase 2 (CK2) increased activated proten C cofactor activity. (PMID:23580615)
• CSNK1alpha1 has a role in mediating malignant plasma cell survival (PMID:24962017)
• Casein kinase 1 alpha specifically phosphorylates Jade-1 at an unprimed SLS phosphorylation site. (PMID:25100726)
• Degradation of Tiam1 by casein kinase 1 and the SCFbetaTrCP ubiquitin ligase controls the duration of mTOR-S6K signaling. (PMID:25124033)
• Phosphorylation of LRRK2 by casein kinase 1alpha regulates trans-Golgi clustering via differential interaction with ARHGEF7. (PMID:25500533)
• The dynamical and conformational properties for each of three isoforms of CK1 are explored through molecular dynamics (MD) simulations. (PMID:25665722)
• characterization of frequency and potential clinical impact of CSNK1A1 mutations in myelodysplastic syndrome(MDS) and acute myeloid leukemia following MDS in a large cohort of patients (PMID:25792355)
• Casein kinase 1alpha is a key negative regulator of oncogenic RAS-induced autophagy. Depletion or pharmacologic inhibition of CK1alpha enhanced autophagic flux in oncogenic RAS-driven human fibroblasts and multiple cancer cell lines. (PMID:25798617)
• study focuses on, how the structural dynamics and conformational changes of two CK1 isoforms are synchronized in carcinogenic pathway (PMID:26788877)
• Interactome analyses revealed that the Jade-1S mutant unable to be phosphorylated by CK1alpha has an increased binding affinity to proteins involved in chromatin remodelling, histone deacetylation, transcriptional repression, and ribosome biogenesis. (PMID:26919559)
• NIFK is required for lung cancer progression via the RUNX1-dependent CK1alpha repression, which activates TCF4/beta-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation. (PMID:26984280)
• The study describes the identification of a novel, tumor-specific missense mutation in the active site of casein kinase 1 alpha(CSNK1A1) using activity-based proteomics. (PMID:27031502)
• These data indicate that CK1alpha has a dominant and non-redundant function in melanoma cells (PMID:27488834)
• CK1delta enhances EPO secretion from liver cancer cells under hypoxia by modifying HIF-2alpha and promoting its nuclear accumulation. (PMID:27686097)
• casein kinase 1 phosphorylates the SQSTM1 S349 residue when harmful proteins accumulate under HSF1 stress (PMID:27846364)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	csnk1a1	ENSDARG00000052674
mus_musculus	Csnk1a1	ENSMUSG00000024576
rattus_norvegicus	Csnk1a1	ENSRNOG00000072163
drosophila_melanogaster	CkIalpha	FBGN0015024
drosophila_melanogaster	CG2577	FBGN0030384
drosophila_melanogaster	CG7094	FBGN0032650
drosophila_melanogaster	CG12147	FBGN0037325
caenorhabditis_elegans		WBGENE00002202

Paralogs (12): VRK2 (ENSG00000028116), CDC7 (ENSG00000097046), VRK1 (ENSG00000100749), VRK3 (ENSG00000105053), TTBK2 (ENSG00000128881), CSNK1G2 (ENSG00000133275), CSNK1D (ENSG00000141551), TTBK1 (ENSG00000146216), CSNK1G3 (ENSG00000151292), CSNK1G1 (ENSG00000169118), CSNK1A1L (ENSG00000180138), CSNK1E (ENSG00000213923)

Protein

Protein identifiers

Casein kinase I isoform alpha — P48729 (reviewed: P48729)

Alternative names: CK1

All UniProt accessions (13): A0A590UJ43, A0A590UJQ7, A0A590UK94, A0A5F9W493, P48729, D6REM4, D6RGE5, E5RG27, E7ETM0, H0Y9X2, U3KPX3, U3KQ83, U3KQK7

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. It can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates CTNNB1 at ‘Ser-45’. May phosphorylate PER1 and PER2. May play a role in segregating chromosomes during mitosis. May play a role in keratin cytoskeleton disassembly and thereby, it may regulate epithelial cell migration. Acts as a positive regulator of mTORC1 and mTORC2 signaling in response to nutrients by mediating phosphorylation of DEPTOR inhibitor. Acts as an inhibitor of NLRP3 inflammasome assembly by mediating phosphorylation of NLRP3.

Subunit / interactions. Interacts with the Axin complex. Interacts with TUT1, leading to TUT1 phosphorylation. Interacts with FAM83A, FAM83B, FAM83C, FAM83D, FAM83E, FAM83F, FAM83G and FAM83H (via DUF1669). Interaction with FAM83H recruits CSNK1A1 to keratin filaments.

Subcellular location. Cytoplasm. Cytoskeleton. Microtubule organizing center. Centrosome. Chromosome. Centromere. Kinetochore. Nucleus speckle. Cilium basal body. Spindle.

Post-translational modifications. Phosphorylated by MTOR in response to mitogenic stimulation, leading to its activation.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P48729-1	1	yes
P48729-2	2
P48729-3	3

RefSeq proteins (4): NP_001020276, NP_001258670, NP_001258671, NP_001883* (*=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 (50 total): helix 13, sequence conflict 7, strand 7, turn 6, modified residue 5, splice variant 2, binding site 2, initiator methionine 1, chain 1, sequence variant 1, mutagenesis site 1, domain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
6GZD	X-RAY DIFFRACTION	2.28
5FQD	X-RAY DIFFRACTION	2.45
9OTY	ELECTRON MICROSCOPY	3
7WTT	ELECTRON MICROSCOPY	3.1
8G66	X-RAY DIFFRACTION	3.45

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P48729-F1	92.25	0.86

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): 136 (proton acceptor)

Ligand- & substrate-binding residues (2): 23–31; 46

Post-translational modifications (5): 8, 156, 321, 2, 4

Mutagenesis-validated functional residues (1):

Position	Phenotype
141	catalytically inactive. no effect on interaction with fam83 family members.

Function

Pathways and Gene Ontology

Reactome pathways

35 pathways

ID	Pathway
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716	Signaling by GSK3beta mutants
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated
R-HSA-5467337	APC truncation mutants have impaired AXIN binding
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex
R-HSA-5610783	Degradation of GLI2 by the proteasome
R-HSA-5610785	GLI3 is processed to GLI3R by the proteasome
R-HSA-5635838	Activation of SMO
R-HSA-69601	Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A
R-HSA-9694631	Maturation of nucleoprotein
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-195721	Signaling by WNT
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-4791275	Signaling by WNT in cancer
R-HSA-4839735	Signaling by AXIN mutants
R-HSA-4839743	Signaling by CTNNB1 phospho-site mutants
R-HSA-4839744	Signaling by APC mutants
R-HSA-4839748	Signaling by AMER1 mutants
R-HSA-5358351	Signaling by Hedgehog
R-HSA-5610787	Hedgehog ‘off’ state
R-HSA-5632684	Hedgehog ‘on’ state
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-5663205	Infectious disease

MSigDB gene sets: 396 (showing top): GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CONTAINING_COMPLEX_ASSEMBLY, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_INTERMEDIATE_FILAMENT_BASED_PROCESS, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_INFLAMMATORY_RESPONSE, AAGCCAT_MIR135A_MIR135B, GOBP_POSITIVE_REGULATION_OF_TOR_SIGNALING, GOBP_POSITIVE_REGULATION_OF_RHO_PROTEIN_SIGNAL_TRANSDUCTION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_REGULATION_OF_SMALL_GTPASE_MEDIATED_SIGNAL_TRANSDUCTION

GO Biological Process (25): protein phosphorylation (GO:0006468), Golgi organization (GO:0007030), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), Wnt signaling pathway (GO:0016055), viral protein processing (GO:0019082), cellular response to nutrient (GO:0031670), positive regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032436), positive regulation of Rho protein signal transduction (GO:0035025), proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161), intermediate filament cytoskeleton organization (GO:0045104), cell division (GO:0051301), negative regulation of canonical Wnt signaling pathway (GO:0090090), negative regulation of NLRP3 inflammasome complex assembly (GO:1900226), positive regulation of TORC1 signaling (GO:1904263), autophagosome assembly (GO:0000045), negative regulation of autophagy (GO:0010507), positive regulation of autophagy (GO:0010508), regulation of Wnt signaling pathway (GO:0030111), SCF-dependent proteasomal ubiquitin-dependent protein catabolic process (GO:0031146), cellular response to nutrient levels (GO:0031669), TORC1 signaling (GO:0038202), NLRP3 inflammasome complex assembly (GO:0044546), positive regulation of NLRP3 inflammasome complex assembly (GO:1900227), negative regulation of TORC1 signaling (GO:1904262)

GO Molecular Function (8): 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 (17): kinetochore (GO:0000776), nucleus (GO:0005634), cytoplasm (GO:0005737), centrosome (GO:0005813), spindle (GO:0005819), cytosol (GO:0005829), cilium (GO:0005929), membrane (GO:0016020), nuclear speck (GO:0016607), beta-catenin destruction complex (GO:0030877), ciliary basal body (GO:0036064), chromosome, centromeric region (GO:0000775), chromosome (GO:0005694), mRNA cleavage and polyadenylation specificity factor complex (GO:0005847), cytoskeleton (GO:0005856), cell projection (GO:0042995), keratin filament (GO:0045095)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Signaling by CTNNB1 phospho-site mutants	4
Signaling by WNT	2
Hedgehog ‘off’ state	2
Degradation of beta-catenin by the destruction complex	1
TCF dependent signaling in response to WNT	1
Signaling by WNT in cancer	1
Signaling by APC mutants	1
Signaling by AXIN mutants	1
Signaling by AMER1 mutants	1
Hedgehog ‘on’ state	1
p53-Independent G1/S DNA Damage Checkpoint	1
Translation of Structural Proteins	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membraneless organelle	4
cellular anatomical structure	4
cellular process	2
proteasome-mediated ubiquitin-dependent protein catabolic process	2
autophagy	2
regulation of autophagy	2
protein kinase activity	2
microtubule organizing center	2
phosphorylation	1
protein modification process	1
organelle organization	1
endomembrane system organization	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
signal transduction	1
cell surface receptor signaling pathway	1
viral process	1
viral gene expression	1
response to nutrient	1
cellular response to nutrient levels	1
cellular response to chemical stimulus	1
regulation of proteasomal ubiquitin-dependent protein catabolic process	1
positive regulation of proteasomal protein catabolic process	1
positive regulation of ubiquitin-dependent protein catabolic process	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
positive regulation of small GTPase mediated signal transduction	1
ubiquitin-dependent protein catabolic process	1
proteasomal protein catabolic process	1
cytoskeleton organization	1
intermediate filament-based process	1
negative regulation of Wnt signaling pathway	1
canonical Wnt signaling pathway	1
regulation of canonical Wnt signaling pathway	1
negative regulation of protein-containing complex assembly	1
NLRP3 inflammasome complex assembly	1
negative regulation of inflammasome-mediated signaling pathway	1
regulation of NLRP3 inflammasome complex assembly	1

Protein interactions and networks

STRING

2181 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CSNK1A1	AXIN1	O15169	998
CSNK1A1	GSK3B	P49841	996
CSNK1A1	APC	P25054	994
CSNK1A1	AXIN2	Q9Y2T1	994
CSNK1A1	CTNNB1	P35222	991
CSNK1A1	GSK3A	P49840	968
CSNK1A1	CRBN	Q96SW2	885
CSNK1A1	DVL1	O14640	874
CSNK1A1	MDM2	Q00987	847
CSNK1A1	BTRC	Q9Y297	819
CSNK1A1	AMER1	Q5JTC6	812
CSNK1A1	LRP6	O75581	763
CSNK1A1	MDM4	O15151	756
CSNK1A1	LRP5	O75197	729
CSNK1A1	PTPA	Q15257	703

IntAct

258 interactions, top by confidence:

A	B	Type	Score
IKBKG	IKBKB	psi-mi:“MI:0914”(association)	0.980
CTNNB1	AXIN1	psi-mi:“MI:0914”(association)	0.940
FAM83H	CSNK1A1	psi-mi:“MI:0914”(association)	0.920
FAM83H	CSNK1A1	psi-mi:“MI:0403”(colocalization)	0.920
FAM83H	CSNK1A1	psi-mi:“MI:0915”(physical association)	0.920
FAM83G	CSNK1A1	psi-mi:“MI:0914”(association)	0.900
FAM83G	CSNK1A1	psi-mi:“MI:0915”(physical association)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0403”(colocalization)	0.900
CSNK1A1	FAM83G	psi-mi:“MI:0217”(phosphorylation reaction)	0.900
MAPK14	RPS6KA4	psi-mi:“MI:0914”(association)	0.870
CSNK1A1	FAM83D	psi-mi:“MI:0915”(physical association)	0.830
CSNK1A1	FAM83D	psi-mi:“MI:0403”(colocalization)	0.830
YWHAH	ABLIM1	psi-mi:“MI:0914”(association)	0.800
FAM83B	CSNK1A1	psi-mi:“MI:0914”(association)	0.800

BioGRID (576): CSNK1A1 (Reconstituted Complex), CSNK1A1 (Affinity Capture-MS), TOM20 (Biochemical Activity), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Proximity Label-MS), CSNK1A1 (Affinity Capture-MS), CSNK1A1 (Proximity Label-MS), CSNK1A1 (Proximity Label-MS), CSNK1A1 (Proximity Label-MS), CSNK1A1 (Proximity Label-MS)

ESM2 similar proteins: B9VVJ6, O15726, O76324, P35507, P35508, P40235, P40236, P42168, P48729, P48730, P49674, P54367, P67827, P67828, P67829, P67962, P67963, P78368, P97633, Q06486, Q39050, Q4R9A9, Q5BP74, Q5PRD4, Q5R4V3, Q5RC72, Q5ZLL1, Q62761, Q62762, Q62763, Q6P3K7, Q6P647, Q6QNL9, Q6QNM1, Q7RBX5, Q7T2E3, Q8BK63, Q8BVP5, Q8C4X2, Q8IHZ9

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

104 interactions.

A	Effect	B	Mechanism
CSNK1A1	“down-regulates activity”	NFATC3	phosphorylation
CSNK1A1	down-regulates	GLI3	phosphorylation
CSNK1A1	up-regulates	LGALS3	phosphorylation
CSNK1A1	down-regulates	HNRNPC	phosphorylation
CSNK1A1	“down-regulates activity”	HNRNPC	phosphorylation
CSNK1A1	“down-regulates activity”	FADD	phosphorylation
CSNK1A1	up-regulates	LRP6	phosphorylation
CSNK1A1	down-regulates	GLI2	phosphorylation
CSNK1A1	up-regulates	FOXG1	phosphorylation
CSNK1A1	unknown	TP53	phosphorylation
CSNK1A1	down-regulates	FOXO3	phosphorylation
CSNK1A1	down-regulates	CDC25A	phosphorylation
CSNK1A1	down-regulates	CTNNB1	phosphorylation
CSNK1A1	down-regulates	CTPS2	phosphorylation
CSNK1A1	up-regulates	SMO	phosphorylation
CSNK1A1	down-regulates	DEPTOR	phosphorylation
CSNK1A1	“up-regulates activity”	GSK3B	binding
CSNK1A1	down-regulates	RHOB	phosphorylation
CSNK1A1	down-regulates	FOXO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 174 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
Regulation of NF-kappa B signaling	5	27.8×	8e-05
TICAM1, RIP1-mediated IKK complex recruitment	5	26.4×	8e-05
Regulation of necroptotic cell death	6	23.1×	3e-05
IKK complex recruitment mediated by RIP1	5	21.8×	2e-04
TNFR1-induced NF-kappa-B signaling pathway	7	20.6×	2e-05
Regulation of TNFR1 signaling	8	15.7×	2e-05
NOD1/2 Signaling Pathway	5	13.9×	7e-04
Activation of NF-kappaB in B cells	7	12.1×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	10	25.6×	6e-09
obsolete positive regulation of NF-kappaB transcription factor activity	10	14.4×	1e-06
tumor necrosis factor-mediated signaling pathway	6	13.9×	1e-03
negative regulation of canonical NF-kappaB signal transduction	8	9.6×	6e-04
T cell receptor signaling pathway	7	7.4×	8e-03
positive regulation of canonical NF-kappaB signal transduction	14	7.1×	5e-06
protein phosphorylation	10	4.8×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1944 predictions. Top by Δscore:

Variant	Effect	Δscore
5:149505591:GGGTC:G	acceptor_gain	1.0000
5:149505593:GTC:G	acceptor_gain	1.0000
5:149505594:TC:T	acceptor_gain	1.0000
5:149505595:CC:C	acceptor_gain	1.0000
5:149505596:C:CA	acceptor_loss	1.0000
5:149505596:C:CC	acceptor_gain	1.0000
5:149505597:T:C	acceptor_loss	1.0000
5:149507022:CTGA:C	donor_loss	1.0000
5:149507024:GACCT:G	donor_loss	1.0000
5:149507025:ACCT:A	donor_loss	1.0000
5:149507131:CCC:C	acceptor_gain	1.0000
5:149507132:CCCTA:C	acceptor_gain	1.0000
5:149509875:TTA:T	donor_loss	1.0000
5:149509877:A:AC	donor_gain	1.0000
5:149509877:ACC:A	donor_loss	1.0000
5:149509878:C:CG	donor_loss	1.0000
5:149509878:C:CT	donor_gain	1.0000
5:149509878:CCT:C	donor_gain	1.0000
5:149509878:CCTT:C	donor_gain	1.0000
5:149509878:CCTTA:C	donor_gain	1.0000
5:149509949:GCAGC:G	acceptor_gain	1.0000
5:149509950:CAGC:C	acceptor_gain	1.0000
5:149509950:CAGCC:C	acceptor_gain	1.0000
5:149509951:AGC:A	acceptor_gain	1.0000
5:149509952:GC:G	acceptor_gain	1.0000
5:149509953:CCTG:C	acceptor_gain	1.0000
5:149509954:C:CC	acceptor_gain	1.0000
5:149509954:C:CG	acceptor_loss	1.0000
5:149509954:C:T	acceptor_gain	1.0000
5:149509956:G:C	acceptor_gain	1.0000

AlphaMissense

2253 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:149505559:C:A	W298C	1.000
5:149505559:C:G	W298C	1.000
5:149505560:C:G	W298S	1.000
5:149505561:A:G	W298R	1.000
5:149505561:A:T	W298R	1.000
5:149505565:A:C	F296L	1.000
5:149505565:A:T	F296L	1.000
5:149505567:A:G	F296L	1.000
5:149507080:A:C	F268L	1.000
5:149507080:A:T	F268L	1.000
5:149507082:A:G	F268L	1.000
5:149509909:C:A	K240N	1.000
5:149509909:C:G	K240N	1.000
5:149509922:A:C	I236S	1.000
5:149509922:A:T	I236N	1.000
5:149509932:A:G	Y233H	1.000
5:149511806:C:A	W221C	1.000
5:149511806:C:G	W221C	1.000
5:149511808:A:G	W221R	1.000
5:149511808:A:T	W221R	1.000
5:149511813:A:T	L219Q	1.000
5:149511846:C:T	G208E	1.000
5:149511847:C:G	G208R	1.000
5:149511847:C:T	G208R	1.000
5:149511861:T:A	D203V	1.000
5:149511862:C:A	D203Y	1.000
5:149511862:C:G	D203H	1.000
5:149511864:T:A	D202V	1.000
5:149511865:C:A	D202Y	1.000
5:149511865:C:G	D202H	1.000

dbSNP variants (sampled 300 via entrez): RS1000009086 (5:149494181 A>G), RS1000063395 (5:149530049 A>G), RS1000071421 (5:149535879 C>G), RS1000091167 (5:149518355 C>T), RS1000102170 (5:149494505 C>A), RS1000273147 (5:149507516 A>G), RS1000294173 (5:149551720 T>C), RS1000302879 (5:149507275 C>G,T), RS1000400248 (5:149526597 T>A), RS1000416352 (5:149513825 G>A), RS1000426100 (5:149519315 T>C), RS1000475868 (5:149534800 AT>A), RS1000492423 (5:149540025 C>A), RS1000664156 (5:149528483 G>A), RS1000674007 (5:149500462 A>G,T)

Disease associations

OMIM: gene MIM:600505 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): CIC-rearranged sarcoma (MONDO:0956989)

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST001089_2	Esophageal cancer	5.000000e-09
GCST007692_20	Chronic obstructive pulmonary disease	8.000000e-06
GCST010151_14	Carotid intima media thickness x smoking interaction	5.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0006527	smoking status measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (7): CHEMBL2111458 (PROTEIN FAMILY), CHEMBL2793 (SINGLE PROTEIN), CHEMBL3038493 (PROTEIN COMPLEX), CHEMBL3885539 (PROTEIN COMPLEX), CHEMBL4296102 (PROTEIN COMPLEX), CHEMBL4523610 (PROTEIN FAMILY), CHEMBL6195518 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 242,599 (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
CHEMBL1201303	PYRVINIUM	4	1,797
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1789941	RUXOLITINIB	4	11,547
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3301612	ENCORAFENIB	4	4,624
CHEMBL535	SUNITINIB	4	79,020
CHEMBL576982	QUIZARTINIB	4	4,432
CHEMBL428690	ALVOCIDIB	3	27,781
CHEMBL1230165	SILMITASERTIB	2	593
CHEMBL14762	SELICICLIB	2	3,787
CHEMBL1614713	CC-401	2	389
CHEMBL1721885	SU-014813	2	363
CHEMBL1976040	ADAVOSERTIB	2	1,738
CHEMBL2010872	CEP-11981	2	1,252
CHEMBL230011	TG100-115	2	1,504
CHEMBL2364611	GALUNISERTIB	2	1,929
CHEMBL3137336	UPROSERTIB	2	1,624
CHEMBL3545396	BMS-690514	2	567
CHEMBL363648	TAK-715	2	442
CHEMBL513909	BI-2536	2	895
CHEMBL564829	MILCICLIB	2
CHEMBL1908397	KW-2449	1
CHEMBL296468	BMS-387032	1
CHEMBL3545083	RGB-286638	1
CHEMBL4225966	SEL-120 FREE BASE	1
CHEMBL4754493	BTX-A51	1
CHEMBL482967	CYC-116	1
CHEMBL488436	AZD-5438	1
CHEMBL571948	Y-39983	1

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

GtoPdb / IUPHAR curated pharmacology

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

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

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
D4476	Inhibition	6.52	pIC50
compound 14 [PMID: 24900428]	Inhibition	6.35	pIC50
IC261	Inhibition	4.8	pIC50

Binding affinities (BindingDB)

32 measured of 44 human assays (49 total across all organisms); most potent 32 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-pyrazolo[1,5-a]pyridin-2-yl-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.07 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]-2-quinoxalin-2-yl-acetamide	IC50	1.1 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-[4-(2-fluoro-7-pyridin-2-yl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-2-pyridinyl]butanamide	IC50	1.21 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
(2R)-4,4-difluoro-2-(4-fluorophenyl)-N-[4-(7-pyridin-2-yl-5H-pyrrolo[2,3-b]pyrazin-6-yl)-2-pyridinyl]butanamide	IC50	1.25 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-isoxazol-5-yl-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.42 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(2,4-dimethylthiazol-5-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.46 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-isothiazol-5-yl-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.47 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(5-cyclopropylisoxazol-3-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.57 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.62 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(3-methylisoxazol-5-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.69 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(3,5-dimethylisoxazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.71 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(2-methylthiazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.81 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(oxazol-5-yl)-N-(4-(7-(pyridin-2-yl)-5H-pyrrolo[2,3-b]pyrazin-6-yl)pyridin-2-yl)acetamide	IC50	1.82 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]-2-[1-(2,2,2-trifluoroethyl)pyrazol-3-yl]acetamide	IC50	1.88 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(2,5-dimethylpyrazol-3-yl)-N-[4-(3-pyridin-2-yl-1H-pyrrolo[3,2-b]pyridin-2-yl)-2-pyridinyl]acetamide	IC50	1.94 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(2-methyloxazol-5-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.95 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-isoxazol-3-yl-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	1.97 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(5-methylisoxazol-3-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.03 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(5-cyclopropyl-1-methyl-pyrazol-3-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.21 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(1-isopropylpyrazol-3-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.28 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(1,3-dimethylpyrazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.61 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(3-methylisoxazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.62 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(1,5-dimethylpyrazol-3-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.74 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(2-methyloxazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	2.79 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]-2-(1,3,5-trimethylpyrazol-4-yl)acetamide	IC50	2.97 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
(2R)-N-[4-[4-(2,2-difluoroethoxy)-7-pyridin-2-yl-5H-pyrrolo[3,2-d]pyrimidin-6-yl]-2-pyridinyl]-4,4-difluoro-2-(4-fluorophenyl)butanamide	IC50	3.1 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(5-methyloxazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	3.43 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(1-methylimidazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	4.12 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-(1-methylpyrazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]acetamide	IC50	4.21 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
US20250188075, Example 1	IC50	5.89 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
4,4-difluoro-2-(1-methylpyrazol-4-yl)-N-[4-[3-(2-pyridyl)-1H-pyrrolo[3,2-b]pyridin-2-yl]-2-pyridyl]butanamide	IC50	6.82 nM	US-20250188075: SUBSTITUTED HETEROCYCLIC CSNK1 INHIBITORS
2-[(3,5-difluoro-4-hydroxyphenyl)amino]-5,7-dimethyl-8-(3-methylbutyl)-5,6,7,8-tetrahydropteridin-6-one	IC50	340 nM

ChEMBL bioactivities

466 potent at pChembl≥5 of 530 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	Kd	1	nM	PYRVINIUM
9.00	EC50	1	nM	CHEMBL5434155
9.00	EC50	1	nM	CHEMBL5401739
9.00	EC50	1	nM	CHEMBL5436432
9.00	EC50	1	nM	CHEMBL5436826
9.00	EC50	1	nM	CHEMBL5441130
9.00	EC50	1	nM	CHEMBL5427472
9.00	EC50	1	nM	CHEMBL5400246
9.00	EC50	1	nM	CHEMBL5395344
9.00	EC50	1	nM	CHEMBL5426981
9.00	EC50	1	nM	CHEMBL5424205
8.40	IC50	4	nM	SILMITASERTIB
8.28	IC50	5.3	nM	BTX-A51
8.28	Kd	5.3	nM	CHEMBL5569495
8.14	IC50	7.2	nM	CHEMBL5303449
8.10	Ki	7.943	nM	CHEMBL1965660
8.10	Ki	7.943	nM	CHEMBL1993904
8.05	IC50	9	nM	CHEMBL2203552
8.01	Kd	9.8	nM	CHEMBL5571313
7.90	Ki	12.59	nM	CHEMBL1997335
7.90	Ki	12.59	nM	SB-220025
7.85	IC50	14	nM	CHEMBL215919
7.85	IC50	14	nM	CHEMBL5303449
7.85	IC50	14	nM	CHEMBL1080583
7.80	Ki	15.85	nM	CHEMBL1981079
7.80	Ki	15.85	nM	CHEMBL1973720
7.72	IC50	19	nM	CHEMBL2203555
7.50	Ki	31.62	nM	CHEMBL225519
7.50	Ki	31.62	nM	CHEMBL1983575
7.48	IC50	33	nM	CHEMBL2203553
7.46	IC50	35	nM	HYMENIALDISINE
7.40	Ki	39.81	nM	CHEMBL1996980
7.40	Ki	39.81	nM	CHEMBL1985681
7.40	Ki	39.81	nM	CHEMBL1081312
7.32	IC50	48	nM	CEP-11981
7.30	Ki	50.12	nM	CHEMBL1966628
7.30	Ki	50.12	nM	CHEMBL1997129
7.30	Ki	50.12	nM	CHEMBL1982700
7.30	Ki	50.12	nM	CHEMBL1993877
7.27	IC50	54	nM	CHEMBL2203556
7.22	IC50	60	nM	CHEMBL3688339
7.20	Ki	63.1	nM	CHEMBL1986943
7.20	Ki	63.1	nM	CHEMBL1983715
7.19	EC50	64	nM	CHEMBL6103237
7.14	EC50	72	nM	CHEMBL6103079
7.12	Kd	75	nM	SB-203580
7.11	IC50	78	nM	CHEMBL2089212
7.10	Ki	79.43	nM	CHEMBL2000508
7.10	Ki	79.43	nM	CHEMBL1982271
7.10	Ki	79.43	nM	CHEMBL1999484

PubChem BioAssay actives

144 with measured affinity, of 2114 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
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	507421: Inhibition of recombinant CK1 by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-8-methoxy-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-6-methoxy-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-(trifluoromethoxy)-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-(trifluoromethyl)-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-methyl-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
7-bromo-N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
6,8-dibromo-N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-5-methoxy-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-7-methoxy-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
6-bromo-N-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]-8-methoxy-2H-chromene-3-carboxamide	2025217: Protac activity at CRBN/CK1alpha (unknown origin) transfected in HEK293T cells incubated for 24 hrs by flow cytometry analysis	ec50	0.0010	uM
2-[(E)-2-(2,5-dimethyl-1-phenylpyrrol-3-yl)ethenyl]-N,N,1-trimethylquinolin-1-ium-6-amine	1845988: Binding affinity to CK1alpha (unknown origin) using casein as substrate by fluorescence based analysis	kd	0.0010	uM
Sunitinib	507421: Inhibition of recombinant CK1 by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.0010	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	1868081: Inhibition of CSNK1A1 (unknown origin)	ic50	0.0053	uM
2-(5-methoxy-2-quinolin-3-ylpyrimidin-4-yl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.0090	uM
4-N-[4-[5-(cyclopropylmethyl)-1-methylpyrazol-4-yl]-5-fluoropyrimidin-2-yl]cyclohexane-1,4-diamine	2103775: Binding affinity to CK1alpha (unknown origin) assessed as dissociation constant	kd	0.0098	uM
(2R)-2-[[9-propan-2-yl-6-(3-pyridin-2-ylanilino)purin-2-yl]amino]butan-1-ol	684955: Inhibition of CK1 using KRRRALS(p)VASLPGL as substrate after 40 mins by scintillation counter	ic50	0.0140	uM
2-[[9-propan-2-yl-6-(3-pyridin-2-ylanilino)purin-2-yl]amino]butan-1-ol	463857: Inhibition of CK1	ic50	0.0140	uM
2-[2-(benzylamino)-5-methoxypyrimidin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.0190	uM
2-[2-[(E)-2-(4-fluorophenyl)ethenyl]-5-methoxypyrimidin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	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
19-methyl-3-(2-methylpropyl)-7-(pyrimidin-2-ylamino)-3,13,19,20-tetrazahexacyclo[14.7.0.02,10.04,9.011,15.017,21]tricosa-1(16),2(10),4(9),5,7,11(15),17,20-octaen-14-one	653717: Inhibition of CK1 using ATP as substrate	ic50	0.0480	uM
2-(2-anilino-5-methoxypyrimidin-4-yl)-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.0540	uM
4-[4-(4-fluorophenyl)-2-(4-methylsulfinylphenyl)-1H-imidazol-5-yl]pyridine	624846: Binding constant for CSNK1A1 kinase domain	kd	0.0750	uM
1-[3-[(3-amino-2H-pyrazolo[3,4-d]pyrimidin-6-yl)amino]phenyl]-3-(3-chloro-4-fluorophenyl)urea	684955: Inhibition of CK1 using KRRRALS(p)VASLPGL as substrate after 40 mins by scintillation counter	ic50	0.0780	uM
2-[2-[(4-fluorophenyl)methoxy]-5-methoxypyrimidin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.0950	uM
5,6-dibromo-4-(difluoromethyl)-1-(oxan-4-yl)-2-piperazin-1-ylbenzimidazole	2070984: Inhibition of CSNK1A1 (unknown origin) by ADP-Glo assay	ic50	0.1323	uM
1-[3-[(3-amino-2H-pyrazolo[3,4-d]pyrimidin-6-yl)amino]phenyl]-3-(5-tert-butyl-1H-pyrazol-3-yl)urea	684955: Inhibition of CK1 using KRRRALS(p)VASLPGL as substrate after 40 mins by scintillation counter	ic50	0.1420	uM
2-[2-[(4-fluorophenoxy)methyl]-5-methoxypyrimidin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.1460	uM
[(2R)-2-hydroxy-3-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]propyl] (2S)-2-amino-3-methylbutanoate;hydrochloride	682604: Inhibition of CK1 after 30 mins by liquid scintillation counter	ic50	0.1500	uM
2,2,2-trichloroethyl (1S)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]cycloprop-2-ene-1-carboxylate	2130918: Induction of ePL tagged CK1alpha degradation in human MDS-L cells incubated for 60 mins by luminescence reader assay	ec50	0.1700	uM
2-[2-[(4-fluorophenoxy)methyl]-5-methoxy-4-pyridinyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.1740	uM
(2R)-3-[[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]amino]propane-1,2-diol	682604: Inhibition of CK1 after 30 mins by liquid scintillation counter	ic50	0.1800	uM
9-bromo-2-(furan-2-yl)-[1,2,4]triazolo[1,5-c]quinazolin-5-amine	1849001: Inhibition of CK1alpha (unknown origin)	ic50	0.2200	uM
trans-2,2,2-trichloroethyl (1S,2R)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]cyclopropane-1-carboxylate	2130918: Induction of ePL tagged CK1alpha degradation in human MDS-L cells incubated for 60 mins by luminescence reader assay	ec50	0.2200	uM
2-[2-[(2,4-difluorophenoxy)methyl]-5-methoxy-4-pyridinyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.2250	uM
1-(4-methyl-2,5-dipyridin-4-yl-1H-pyrrol-3-yl)ethanone	389086: Binding affinity to human CK1alpha2	kd	0.2250	uM
N-[3-chloro-4-(4-methylpiperazin-1-yl)phenyl]-2-[4-(5,7-dimethoxy-4-oxo-3H-quinazolin-2-yl)phenoxy]acetamide	1831537: Inhibition of CK1 (unknown origin)	ic50	0.2300	uM
4-[6-[4-(2-piperidin-1-ylethoxy)phenyl]pyrazolo[1,5-a]pyrimidin-3-yl]-N-(2,2,2-trifluoroethyl)thiophene-2-carboxamide	1637068: Inhibition of recombinant human GST-tagged cytoplasmic CSNK1A1 expressed in baculovirus expression system by Z’-LYTE assay	ic50	0.2300	uM
3-[[(1R)-1-phenylethyl]amino]-4-(pyridin-4-ylamino)cyclobut-3-ene-1,2-dione	684955: Inhibition of CK1 using KRRRALS(p)VASLPGL as substrate after 40 mins by scintillation counter	ic50	0.2500	uM
2,2,2-trichloroethyl (1R)-1-(4-bromophenyl)-2-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-5-yl]cycloprop-2-ene-1-carboxylate	2130918: Induction of ePL tagged CK1alpha degradation in human MDS-L cells incubated for 60 mins by luminescence reader assay	ec50	0.2500	uM
Sorafenib	507421: Inhibition of recombinant CK1 by radioactive phosphotransfer assay in presence of 10 uM ATP	ic50	0.2500	uM
2-[2-[(3,4-difluorophenoxy)methyl]-5-methoxy-4-pyridinyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.2510	uM
Bosutinib	624846: Binding constant for CSNK1A1 kinase domain	kd	0.2800	uM
4-[4-(2,3-dihydro-1,4-benzodioxin-6-yl)-5-pyridin-2-yl-1H-imidazol-2-yl]benzamide	1539768: Inhibition of human CK1 in presence of [gamma33P]-ATP	ic50	0.3000	uM
7,8-dichloro-9-methyl-1-oxospiro[2,4-dihydropyrido[3,4-b]indole-3,4’-piperidine]-4-carbonitrile	643846: Inhibition of CK1alpha using ATP as substrate	ic50	0.3300	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	624846: Binding constant for CSNK1A1 kinase domain	kd	0.3600	uM
2-[2-[(4,5-difluoro-2-methylphenoxy)methyl]-5-methoxy-4-pyridinyl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-one	712791: Inhibition of CK1-alpha using biotin[long chain]-KKRRRAL{pS}VATLPGL substrate in presence of 8 uM ATP	ic50	0.3830	uM
(3R,5S)-5-(hydroxymethyl)-1-[9-propan-2-yl-6-[(4-pyridin-2-ylphenyl)methylamino]purin-2-yl]pyrrolidin-3-ol	682604: Inhibition of CK1 after 30 mins by liquid scintillation counter	ic50	0.3900	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression	3
bisphenol A	affects expression, decreases expression, decreases phosphorylation, decreases reaction	2
sodium arsenite	increases expression	2
pyrvinium	increases expression, decreases activity	2
FR900359	decreases phosphorylation	1
methylmercuric chloride	decreases expression, increases expression	1
testosterone undecanoate	affects cotreatment, decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases activity, decreases reaction, increases phosphorylation	1
cobaltous chloride	increases expression	1
N-(2-aminoethyl)-5-chloroisoquinoline-8-sulfonamide	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
pentabromodiphenyl ether	increases expression	1
CGP 52608	affects binding, increases reaction	1
deguelin	decreases expression	1
U 0126	affects expression, affects reaction	1
K 7174	increases expression	1
IC 261	decreases activity, decreases reaction, increases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
Resveratrol	increases expression, affects cotreatment	1
Sunitinib	increases expression	1
Lenalidomide	decreases expression, increases degradation	1
Leflunomide	increases expression	1
Cisplatin	increases expression, decreases reaction	1
Coumestrol	decreases expression	1
Demecolcine	increases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Piroxicam	decreases reaction, increases expression	1

ChEMBL screening assays

518 unique, capped per target: 514 binding, 4 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
CHEMBL1963741	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: CSNK1A1	PubChem BioAssay data set

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0B3	Ubigene HeLa CSNK1A1 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02389244	PHASE2	ACTIVE_NOT_RECRUITING	A Phase II Study Evaluating Efficacy and Safety of Regorafenib in Patients With Metastatic Bone Sarcomas
NCT06414434	PHASE1	ACTIVE_NOT_RECRUITING	BTX-A51 in Patients With Liposarcoma or CIC-rearranged Sarcoma
NCT06820957	PHASE2/PHASE3	ACTIVE_NOT_RECRUITING	Testing a New Combination of Anti-cancer Drugs in Patients Newly Diagnosed With Ewing Sarcoma Who Have Cancer That Has Spread to Other Parts of the Body