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casein kinase 1 epsilon

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Target id: 1998

Nomenclature: casein kinase 1 epsilon

Abbreviated Name: CK1-E

Family: Casein kinase 1 (CK1) family

Contents:

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 416 22q13.1 CSNK1E casein kinase 1 epsilon
Mouse - 416 15 E1 Csnk1e casein kinase 1, epsilon
Rat - 416 7 q34 Csnk1e casein kinase 1, epsilon
Previous and Unofficial Names Click here for help
CKI epsilon | CKIE | casein kinase 1
Database Links Click here for help
Alphafold P49674 (Hs), Q9JMK2 (Mm)
BRENDA 2.7.11.1
ChEMBL Target CHEMBL4937 (Hs)
Ensembl Gene ENSG00000213923 (Hs), ENSMUSG00000022433 (Mm), ENSRNOG00000013076 (Rn)
Entrez Gene 1454 (Hs), 27373 (Mm), 58822 (Rn)
Human Protein Atlas ENSG00000213923 (Hs)
KEGG Enzyme 2.7.11.1
KEGG Gene hsa:1454 (Hs), mmu:27373 (Mm), rno:58822 (Rn)
OMIM 600863 (Hs)
Pharos P49674 (Hs)
RefSeq Nucleotide NM_001894 (Hs), NM_013767 (Mm), NM_031617 (Rn)
RefSeq Protein NP_001885 (Hs), NP_038795 (Mm), NP_113805 (Rn)
UniProtKB P49674 (Hs), Q9JMK2 (Mm)
Wikipedia CSNK1E (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of apo CK1ε.
PDB Id:  4HOK
Resolution:  2.77Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of CK1ε in complex with PF-4800567.
PDB Id:  4HNI
Ligand:  PF-4800567
Resolution:  2.74Å
Species:  Human
References:  6
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of Casein kinase I isoform delta (CK1 delta) complexed with SR4133 inhibitor
PDB Id:  6RCH
Ligand:  SR-4133
Resolution:  1.45Å
Species:  Human
References:  3
Enzyme Reaction Click here for help
EC Number: 2.7.11.1

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
umbralisib Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Inhibition 5.2 pEC50 5
⤷ pEC50 5.2 (EC50 6x10-6 M) [5]
PF-670462 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 8.1 pIC50 2
⤷ pIC50 8.1 (IC50 7.7x10-9 M) [2]
Description: In a biochemical kinase assay.
PF-4800567 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Inhibition 7.5 pIC50 8
⤷ pIC50 7.5 (IC50 3.2x10-8 M) [8]
SR-4133 Small molecule or natural product Primary target of this compound Ligand has a PDB structure Hs Inhibition 7.2 pIC50 3
⤷ pIC50 7.2 (IC50 5.8x10-8 M) [3]
IC261 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.0 pIC50 7
⤷ pIC50 6.0 (IC50 1x10-6 M) [7]
DiscoveRx KINOMEscan® screen Click here for help
A screen of 72 inhibitors against 456 human kinases. Quantitative data were derived using DiscoveRx KINOMEscan® platform.
http://www.discoverx.com/services/drug-discovery-development-services/kinase-profiling/kinomescan
Reference: 4,9
Key to terms and symbols Click column headers to sort
Target used in screen: CSNK1E
Ligand Sp. Type Action Value Parameter
sunitinib Small molecule or natural product Approved drug Ligand has a PDB structure Hs Inhibitor Inhibition 7.9 pKd
PP-242 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.5 pKd
staurosporine Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 7.1 pKd
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 7.0 pKd
A-674563 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
GDC-0879 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.9 pKd
neratinib Small molecule or natural product Approved drug Hs Inhibitor Inhibition 6.5 pKd
SU-14813 Small molecule or natural product Hs Inhibitor Inhibition 6.5 pKd
BI-2536 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 6.4 pKd
Displaying the top 10 most potent ligands  View all ligands in screen »
EMD Millipore KinaseProfilerTM screen/Reaction Biology Kinase HotspotSM screen Click here for help
A screen profiling 158 kinase inhibitors (Calbiochem Protein Kinase Inhibitor Library I and II, catalogue numbers 539744 and 539745) for their inhibitory activity at 1µM and 10µM against 234 human recombinant kinases using the EMD Millipore KinaseProfilerTM service.

A screen profiling the inhibitory activity of 178 commercially available kinase inhibitors at 0.5µM against a panel of 300 recombinant protein kinases using the Reaction Biology Corporation Kinase HotspotSM platform.

http://www.millipore.com/techpublications/tech1/pf3036
http://www.reactionbiology.com/webapps/main/pages/kinase.aspx

Reference: ...1
Key to terms and symbols Click column headers to sort
Target used in screen: nd/CK1epsilon
Ligand Sp. Type Action % Activity remaining at 0.5µM % Activity remaining at 1µM % Activity remaining at 10µM
PP1 analog II Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 1.5
SB220025 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 2.4
bosutinib Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 11.4
PD 169316 Small molecule or natural product Hs Inhibitor Inhibition 17.3
isogranulatimide Small molecule or natural product Hs Inhibitor Inhibition 18.9
SKF-86002 Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 20.0
Lck inhibitor Small molecule or natural product Ligand has a PDB structure Hs Inhibitor Inhibition 22.3
SP600125 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 25.2
SB203580 Small molecule or natural product Immunopharmacology Ligand Hs Inhibitor Inhibition 31.0
SB202190 Small molecule or natural product Ligand has a PDB structure Immunopharmacology Ligand Hs Inhibitor Inhibition 32.7
Displaying the top 10 most potent ligands  View all ligands in screen »
Immuno Process Associations
Immuno Process:  Antigen presentation

References

Show »

1. Anastassiadis T, Deacon SW, Devarajan K, Ma H, Peterson JR. (2011) Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1039-45. [PMID:22037377]

2. Badura L, Swanson T, Adamowicz W, Adams J, Cianfrogna J, Fisher K, Holland J, Kleiman R, Nelson F, Reynolds L et al.. (2007) An inhibitor of casein kinase I epsilon induces phase delays in circadian rhythms under free-running and entrained conditions. J Pharmacol Exp Ther, 322 (2): 730-8. [PMID:17502429]

3. Choi JY, Noguchi Y, Alburger JM, Bayle S, Chung E, Grant W, Chaikuad A, Knapp S, Duckett DR, Roush WR. (2023) Structure-Based Development of Isoform-Selective Inhibitors of Casein Kinase 1ε vs Casein Kinase 1δ. J Med Chem, 66 (11): 7162-7178. [PMID:37204207]

4. Davis MI, Hunt JP, Herrgard S, Ciceri P, Wodicka LM, Pallares G, Hocker M, Treiber DK, Zarrinkar PP. (2011) Comprehensive analysis of kinase inhibitor selectivity. Nat Biotechnol, 29 (11): 1046-51. [PMID:22037378]

5. Deng C, Lipstein MR, Scotto L, Jirau Serrano XO, Mangone MA, Li S, Vendome J, Hao Y, Xu X, Deng SX et al.. (2017) Silencing c-Myc translation as a therapeutic strategy through targeting PI3Kδ and CK1ε in hematological malignancies. Blood, 129 (1): 88-99. [PMID:27784673]

6. Long AM, Zhao H, Huang X. (2012) Structural basis for the potent and selective inhibition of casein kinase 1 epsilon. J Med Chem, 55 (22): 10307-11. [PMID:23106386]

7. Mashhoon N, DeMaggio AJ, Tereshko V, Bergmeier SC, Egli M, Hoekstra MF, Kuret J. (2000) Crystal structure of a conformation-selective casein kinase-1 inhibitor. J Biol Chem, 275 (26): 20052-60. [PMID:10749871]

8. Walton KM, Fisher K, Rubitski D, Marconi M, Meng QJ, Sládek M, Adams J, Bass M, Chandrasekaran R, Butler T et al.. (2009) Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther, 330 (2): 430-9. [PMID:19458106]

9. Wodicka LM, Ciceri P, Davis MI, Hunt JP, Floyd M, Salerno S, Hua XH, Ford JM, Armstrong RC, Zarrinkar PP et al.. (2010) Activation state-dependent binding of small molecule kinase inhibitors: structural insights from biochemistry. Chem Biol, 17 (11): 1241-9. [PMID:21095574]

How to cite this page

Casein kinase 1 (CK1) family: casein kinase 1 epsilon. Last modified on 23/05/2023. Accessed on 18/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetomalariapharmacology.org/GRAC/ObjectDisplayForward?objectId=1998.