Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTA8PLI)

• DTT Name: Casein kinase I epsilon (CSNK1E)
• Synonyms: Casein kinase I isoform epsilon; CKIe; CKI-epsilon
• Gene Name: CSNK1E
• DTT Type: Successful target; [1]
• BioChemical Class: Kinase
• UniProt ID: KC1E_HUMAN
• TTD ID: T99989
• EC Number: EC 2.7.11.1
• Sequence:
  MELRVGNKYRLGRKIGSGSFGDIYLGANIASGEEVAIKLECVKTKHPQLHIESKFYKMMQ
  GGVGIPSIKWCGAEGDYNVMVMELLGPSLEDLFNFCSRKFSLKTVLLLADQMISRIEYIH
  SKNFIHRDVKPDNFLMGLGKKGNLVYIIDFGLAKKYRDARTHQHIPYRENKNLTGTARYA
  SINTHLGIEQSRRDDLESLGYVLMYFNLGSLPWQGLKAATKRQKYERISEKKMSTPIEVL
  CKGYPSEFSTYLNFCRSLRFDDKPDYSYLRQLFRNLFHRQGFSYDYVFDWNMLKFGAARN
  PEDVDRERREHEREERMGQLRGSATRALPPGPPTGATANRLRSAAEPVASTPASRIQPAG
  NTSPRAISRVDRERKVSMRLHRGAPANVSSSDLTGRQEVSRIPASQTSVPFDHLGK
• Function: Can phosphorylate a large number of proteins. Participates in Wnt signaling. Phosphorylates DVL1 and DVL2. 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. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates.
• KEGG Pathway:
  FoxO signaling pathway (hsa04068)
  Wnt signaling pathway (hsa04310)
  Hedgehog signaling pathway (hsa04340)
  Hippo signaling pathway (hsa04390)
  Hippo signaling pathway - multiple species (hsa04392)
  Circadian rhythm (hsa04710)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
• Reactome Pathway:
  Regulation of PLK1 Activity at G2/M Transition (R-HSA-2565942)
  Loss of Nlp from mitotic centrosomes (R-HSA-380259)
  Recruitment of mitotic centrosome proteins and complexes (R-HSA-380270)
  Loss of proteins required for interphase microtubule organization from the centrosome (R-HSA-380284)
  Recruitment of NuMA to mitotic centrosomes (R-HSA-380320)
  Circadian Clock (R-HSA-400253)
  Anchoring of the basal body to the plasma membrane (R-HSA-5620912)
  Major pathway of rRNA processing in the nucleolus and cytosol (R-HSA-6791226)
  AURKA Activation by TPX2 (R-HSA-8854518)
  WNT mediated activation of DVL (R-HSA-201688)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Umbralisib	DMYRBO1	Follicular lymphoma	2A80	Approved	[2]

3 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IC261	DMXB95R	Pancreatic cancer	2C10	Preclinical	[1]
PF-4800567	DM8P9ST	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[3]
PF-670462	DMTJBP9	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[4]

References

• [1] Crystal structure of a conformation-selective casein kinase-1 inhibitor. J Biol Chem. 2000 Jun 30;275(26):20052-60.
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2021
• [3] Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther. 2009 Aug;330(2):430-9.
• [4] Casein kinase 1 is a therapeutic target in chronic lymphocytic leukemia. Blood. 2018 Mar 15;131(11):1206-1218.