Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTFQI4H)

• DTT Name: Tankyrase-2 (TNKS-2)
• Synonyms: Tankyrase-related protein; Tankyrase-like protein; Tankyrase II; TRF1-interacting ankyrin-related ADP-ribose polymerase 2; TNKL; TANK2; Protein poly-ADP-ribosyltransferase tankyrase-2; Poly [ADP-ribose] polymerase tankyrase-2; Poly [ADP-ribose] polymerase 5B; PARP5B; ARTD6; ADP-ribosyltransferase diphtheria toxin-like 6
• Gene Name: TNKS2
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Glycosyltransferases
• UniProt ID: TNKS2_HUMAN
• TTD ID: T38087
• EC Number: EC 2.4.2.30
• Sequence:
  MSGRRCAGGGAACASAAAEAVEPAARELFEACRNGDVERVKRLVTPEKVNSRDTAGRKST
  PLHFAAGFGRKDVVEYLLQNGANVQARDDGGLIPLHNACSFGHAEVVNLLLRHGADPNAR
  DNWNYTPLHEAAIKGKIDVCIVLLQHGAEPTIRNTDGRTALDLADPSAKAVLTGEYKKDE
  LLESARSGNEEKMMALLTPLNVNCHASDGRKSTPLHLAAGYNRVKIVQLLLQHGADVHAK
  DKGDLVPLHNACSYGHYEVTELLVKHGACVNAMDLWQFTPLHEAASKNRVEVCSLLLSYG
  ADPTLLNCHNKSAIDLAPTPQLKERLAYEFKGHSLLQAAREADVTRIKKHLSLEMVNFKH
  PQTHETALHCAAASPYPKRKQICELLLRKGANINEKTKEFLTPLHVASEKAHNDVVEVVV
  KHEAKVNALDNLGQTSLHRAAYCGHLQTCRLLLSYGCDPNIISLQGFTALQMGNENVQQL
  LQEGISLGNSEADRQLLEAAKAGDVETVKKLCTVQSVNCRDIEGRQSTPLHFAAGYNRVS
  VVEYLLQHGADVHAKDKGGLVPLHNACSYGHYEVAELLVKHGAVVNVADLWKFTPLHEAA
  AKGKYEICKLLLQHGADPTKKNRDGNTPLDLVKDGDTDIQDLLRGDAALLDAAKKGCLAR
  VKKLSSPDNVNCRDTQGRHSTPLHLAAGYNNLEVAEYLLQHGADVNAQDKGGLIPLHNAA
  SYGHVDVAALLIKYNACVNATDKWAFTPLHEAAQKGRTQLCALLLAHGADPTLKNQEGQT
  PLDLVSADDVSALLTAAMPPSALPSCYKPQVLNGVRSPGATADALSSGPSSPSSLSAASS
  LDNLSGSFSELSSVVSSSGTEGASSLEKKEVPGVDFSITQFVRNLGLEHLMDIFEREQIT
  LDVLVEMGHKELKEIGINAYGHRHKLIKGVERLISGQQGLNPYLTLNTSGSGTILIDLSP
  DDKEFQSVEEEMQSTVREHRDGGHAGGIFNRYNILKIQKVCNKKLWERYTHRRKEVSEEN
  HNHANERMLFHGSPFVNAIIHKGFDERHAYIGGMFGAGIYFAENSSKSNQYVYGIGGGTG
  CPVHKDRSCYICHRQLLFCRVTLGKSFLQFSAMKMAHSPPGHHSVTGRPSVNGLALAEYV
  IYRGEQAYPEYLITYQIMRPEGMVDG
• Function: Acts as an activator of the Wnt signaling pathway by mediating poly-ADP-ribosylation of AXIN1 and AXIN2, 2 key components of the beta-catenin destruction complex: poly-ADP-ribosylated target proteins are recognized by RNF146, which mediates their ubiquitination and subsequent degradation. Also mediates poly-ADP-ribosylation of BLZF1 and CASC3, followed by recruitment of RNF146 and subsequent ubiquitination. Mediates poly-ADP-ribosylation of TERF1, thereby contributing to the regulation of telomere length. Stimulates 26S proteasome activity. Poly-ADP-ribosyltransferase involved in various processes such as Wnt signaling pathway, telomere length and vesicle trafficking.
• Reactome Pathway:
  Degradation of AXIN (R-HSA-4641257)
  XAV939 stabilizes AXIN (R-HSA-5545619)
  Ub-specific processing proteases (R-HSA-5689880)
  Regulation of PTEN stability and activity (R-HSA-8948751)
  TCF dependent signaling in response to WNT (R-HSA-201681)

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID27841036-Compound-37	DM0OVZ2	Ovarian cancer	2C73	Phase 2	[1]
Stenoparib	DMKVBL8	Ovarian cancer	2C73	Phase 2	[2]

References

• [1] PARP inhibitors as antitumor agents: a patent update (2013-2015).Expert Opin Ther Pat. 2017 Mar;27(3):363-382.
• [2] Clinical pipeline report, company report or official report of Allarity Therapeutics.