Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Casein kinase I alpha (CSNK1A1)
• Synonyms: Casein kinase I isoform alpha; CKI-alpha; CK1
• Gene Name: CSNK1A1
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Kinase
• UniProt ID: KC1A_HUMAN
• TTD ID: T13075
• EC Number: EC 2.7.11.1
• Sequence:
  MASSSGSKAEFIVGGKYKLVRKIGSGSFGDIYLAINITNGEEVAVKLESQKARHPQLLYE
  SKLYKILQGGVGIPHIRWYGQEKDYNVLVMDLLGPSLEDLFNFCSRRFTMKTVLMLADQM
  ISRIEYVHTKNFIHRDIKPDNFLMGIGRHCNKLFLIDFGLAKKYRDNRTRQHIPYREDKN
  LTGTARYASINAHLGIEQSRRDDMESLGYVLMYFNRTSLPWQGLKAATKKQKYEKISEKK
  MSTPVEVLCKGFPAEFAMYLNYCRGLRFEEAPDYMYLRQLFRILFRTLNHQYDYTFDWTM
  LKQKAAQQAASSSGQGQQAQTPTGKQTDKTKSNMKGF
• Function: 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. Casein kinases are operationally defined by their preferential utilization of acidic proteins such as caseins as substrates.
• KEGG Pathway:
  Wnt signaling pathway (hsa04310)
  Hedgehog signaling pathway (hsa04340)
  Alzheimer disease (hsa05010)
  Pathways of neurodegeneration - multiple diseases (hsa05022)
  Human papillomavirus infection (hsa05165)
  Breast cancer (hsa05224)
  Hepatocellular carcinoma (hsa05225)
  Gastric cancer (hsa05226)
• Reactome Pathway:
  Beta-catenin phosphorylation cascade (R-HSA-196299)
  Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)
  Signaling by GSK3beta mutants (R-HSA-5339716)
  CTNNB1 S33 mutants aren't phosphorylated (R-HSA-5358747)
  CTNNB1 S37 mutants aren't phosphorylated (R-HSA-5358749)
  CTNNB1 S45 mutants aren't phosphorylated (R-HSA-5358751)
  CTNNB1 T41 mutants aren't phosphorylated (R-HSA-5358752)
  APC truncation mutants have impaired AXIN binding (R-HSA-5467337)
  AXIN missense mutants destabilize the destruction complex (R-HSA-5467340)
  Truncations of AMER1 destabilize the destruction complex (R-HSA-5467348)
  Degradation of GLI2 by the proteasome (R-HSA-5610783)
  GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785)
  Activation of SMO (R-HSA-5635838)
  Maturation of nucleoprotein (R-HSA-9694631)
  Degradation of beta-catenin by the destruction complex (R-HSA-195253)

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
BTX-A51	DMC8XHQ	Advanced solid tumour	2A00-2F9Z	Phase 1	[2]

1 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
US9096594, 3	DM8UOKE	N. A.	N. A.	Patented	[3]

2 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
D-4476	DMHD3R8	Chronic lymphocytic leukaemia	2A82.0	Preclinical	[4]
IC261	DMXB95R	Pancreatic cancer	2C10	Preclinical	[1]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID24900428C14	DMU4BL2	Discovery agent	N.A.	Investigative	[5]

References

• [1] Crystal structure of a conformation-selective casein kinase-1 inhibitor. J Biol Chem. 2000 Jun 30;275(26):20052-60.
• [2] Clinical pipeline report, company report or official report of BioTheryX.
• [3] Kinase inhibitors and methods of use thereof. US9096594.
• [4] Discovery of N6-phenyl-1H-pyrazolo[3,4-d]pyrimidine-3,6-diamine derivatives as novel CK1 inhibitors using common-feature pharmacophore model based virtual screening and hit-to-lead optimization. Eur J Med Chem. 2012 Oct;56:30-8.
• [5] Structure-Based Design of Potent and Selective CK1gamma Inhibitors. ACS Med Chem Lett. 2012 Oct 18;3(12):1059-64.