Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Beta-catenin (CTNNB1)
• Synonyms: Wnt/beta-catenin signaling pathway; PRO2286; OK/SW-cl.35; Catenin beta-1; CTNNB
• Gene Name: CTNNB1
• DTT Type: Successful target; [1]
• BioChemical Class: Beta-catenin
• UniProt ID: CTNB1_HUMAN
• TTD ID: T82795
• Sequence:
  MATQADLMELDMAMEPDRKAAVSHWQQQSYLDSGIHSGATTTAPSLSGKGNPEEEDVDTS
  QVLYEWEQGFSQSFTQEQVADIDGQYAMTRAQRVRAAMFPETLDEGMQIPSTQFDAAHPT
  NVQRLAEPSQMLKHAVVNLINYQDDAELATRAIPELTKLLNDEDQVVVNKAAVMVHQLSK
  KEASRHAIMRSPQMVSAIVRTMQNTNDVETARCTAGTLHNLSHHREGLLAIFKSGGIPAL
  VKMLGSPVDSVLFYAITTLHNLLLHQEGAKMAVRLAGGLQKMVALLNKTNVKFLAITTDC
  LQILAYGNQESKLIILASGGPQALVNIMRTYTYEKLLWTTSRVLKVLSVCSSNKPAIVEA
  GGMQALGLHLTDPSQRLVQNCLWTLRNLSDAATKQEGMEGLLGTLVQLLGSDDINVVTCA
  AGILSNLTCNNYKNKMMVCQVGGIEALVRTVLRAGDREDITEPAICALRHLTSRHQEAEM
  AQNAVRLHYGLPVVVKLLHPPSHWPLIKATVGLIRNLALCPANHAPLREQGAIPRLVQLL
  VRAHQDTQRRTSMGGTQQQFVEGVRMEEIVEGCTGALHILARDVHNRIVIRGLNTIPLFV
  QLLYSPIENIQRVAAGVLCELAQDKEAAEAIEAEGATAPLTELLHSRNEGVATYAAAVLF
  RMSEDKPQDYKKRLSVELTSSLFRTEPMAWNETADLGLDIGAQGEPLGYRQDDPSYRSFH
  SGGYGQDALGMDPMMEHEMGGHHPGADYPVDGLPDLGHAQDLMDGLPPGDSNQLAWFDTD
  L
• Function: In the absence of Wnt, forms a complex with AXIN1, AXIN2, APC, CSNK1A1 and GSK3B that promotes phosphorylation on N-terminal Ser and Thr residues and ubiquitination of CTNNB1 via BTRC and its subsequent degradation by the proteasome. In the presence of Wnt ligand, CTNNB1 is not ubiquitinated and accumulates in the nucleus, where it acts as a coactivator for transcription factors of the TCF/LEF family, leading to activate Wnt responsive genes. Involved in the regulation of cell adhesion, as component of an E-cadherin:catenin adhesion complex. Acts as a negative regulator of centrosome cohesion. Involved in the CDK2/PTPN6/CTNNB1/CEACAM1 pathway of insulin internalization. Blocks anoikis of malignant kidney and intestinal epithelial cells and promotes their anchorage-independent growth by down-regulating DAPK2. Disrupts PML function and PML-NB formation by inhibiting RANBP2-mediated sumoylation of PML. Promotes neurogenesis by maintaining sympathetic neuroblasts within the cell cycle. Key downstream component of the canonical Wnt signaling pathway.
• KEGG Pathway:
  Rap1 signaling pathway (hsa04015)
  Wnt signaling pathway (hsa04310)
  Hippo signaling pathway (hsa04390)
  Focal adhesion (hsa04510)
  Adherens junction (hsa04520)
  Tight junction (hsa04530)
  Signaling pathways regulating pluripotency of stem cells (hsa04550)
  Leukocyte transendothelial migration (hsa04670)
  Melanogenesis (hsa04916)
  Thyroid hormone signaling pathway (hsa04919)
  Bacterial invasion of epithelial cells (hsa05100)
  Pathogenic Escherichia coli infection (hsa05130)
  HTLV-I infection (hsa05166)
  Pathways in cancer (hsa05200)
  Proteoglycans in cancer (hsa05205)
  Colorectal cancer (hsa05210)
  Endometrial cancer (hsa05213)
  Prostate cancer (hsa05215)
  Thyroid cancer (hsa05216)
  Basal cell carcinoma (hsa05217)
  Arrhythmogenic right ventricular cardiomyopathy (ARVC) (hsa05412)
• Reactome Pathway:
  Formation of the beta-catenin (R-HSA-201722)
  LRR FLII-interacting protein 1 (LRRFIP1) activates type I IFN production (R-HSA-3134973)
  CDO in myogenesis (R-HSA-375170)
  Deactivation of the beta-catenin transactivating complex (R-HSA-3769402)
  Ca2+ pathway (R-HSA-4086398)
  Binding of TCF/LEF (R-HSA-4411364)
  Disassembly of the destruction complex and recruitment of AXIN to the membrane (R-HSA-4641262)
  S33 mutants of beta-catenin aren't phosphorylated (R-HSA-5358747)
  S37 mutants of beta-catenin aren't phosphorylated (R-HSA-5358749)
  S45 mutants of beta-catenin aren't phosphorylated (R-HSA-5358751)
  T41 mutants of beta-catenin aren't phosphorylated (R-HSA-5358752)
  RHO GTPases activate IQGAPs (R-HSA-5626467)
  TCF dependent signaling in response to WNT (R-HSA-201681)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Recombinant human endostatin	DMMPCFX	Solid tumour/cancer	2A00-2F9Z	Approved	[1]

3 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
C 82	DMEWXFK	Scleroderma	4A42	Phase 1/2	[2]
CEQ-508	DMCR7EF	Familial adenomatous polyposis	2B90.Y	Phase 1/2	[3]
Tegavivint	DMPJ3YX	Desmoid tumour	2F7C	Phase 1	[4]

References

• [1] Endostar, a modified recombinant human endostatin, suppresses angiogenesis through inhibition of Wnt/beta-catenin signaling pathway. PLoS One. 2014 Sep 18;9(9):e107463.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Current Progress of siRNA/shRNA Therapeutics in Clinical Trials. Biotechnol J. 2011 September; 6(9): 1130-1146.
• [4] Tegavivint and the beta-Catenin/ALDH Axis in Chemotherapy-Resistant and Metastatic Osteosarcoma. J Natl Cancer Inst. 2019 Nov 1;111(11):1216-1227.