Details of the Drug Therapeutic Target (DTT)

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

• DTT Name: Apoptosis-2 messenger RNA (BIRC3 mRNA)
• Synonyms: hIAP1 (mRNA); hIAP-1 (mRNA); TNFR2TRAFsignaling complex protein 1 (mRNA); TNFR2-TRAF-signaling complex protein 1 (mRNA); RNF49 (mRNA); RING-type E3 ubiquitin transferase BIRC3 (mRNA); RING finger protein 49 (mRNA); MIHC (mRNA); Inhibitor of apoptosis protein 1 (mRNA); IAP1 (mRNA); IAP homolog C (mRNA); CIAP2 (mRNA); C-IAP2 (mRNA); Baculoviral IAP repeatcontaining protein3 (mRNA); Baculoviral IAP repeat-containing protein 3 (mRNA); Apoptosis inhibitor 2 (mRNA); API2 (mRNA)
• Gene Name: BIRC3
• DTT Type: Literature-reported target; [1]
• BioChemical Class: mRNA target
• UniProt ID: BIRC3_HUMAN
• TTD ID: T59479
• EC Number: EC 2.3.2.27
• Sequence:
  MNIVENSIFLSNLMKSANTFELKYDLSCELYRMSTYSTFPAGVPVSERSLARAGFYYTGV
  NDKVKCFCCGLMLDNWKRGDSPTEKHKKLYPSCRFVQSLNSVNNLEATSQPTFPSSVTNS
  THSLLPGTENSGYFRGSYSNSPSNPVNSRANQDFSALMRSSYHCAMNNENARLLTFQTWP
  LTFLSPTDLAKAGFYYIGPGDRVACFACGGKLSNWEPKDNAMSEHLRHFPKCPFIENQLQ
  DTSRYTVSNLSMQTHAARFKTFFNWPSSVLVNPEQLASAGFYYVGNSDDVKCFCCDGGLR
  CWESGDDPWVQHAKWFPRCEYLIRIKGQEFIRQVQASYPHLLEQLLSTSDSPGDENAESS
  IIHFEPGEDHSEDAIMMNTPVINAAVEMGFSRSLVKQTVQRKILATGENYRLVNDLVLDL
  LNAEDEIREEERERATEEKESNDLLLIRKNRMALFQHLTCVIPILDSLLTAGIINEQEHD
  VIKQKTQTSLQARELIDTILVKGNIAATVFRNSLQEAEAVLYEHLFVQQDIKYIPTEDVS
  DLPVEEQLRRLQEERTCKVCMDKEVSIVFIPCGHLVVCKDCAPSLRKCPICRSTIKGTVR
  TFLS
• Function: Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and regulates both canonical and non-canonical NF-kappa-B signaling by acting in opposite directions: acts as a positive regulator of the canonical pathway and suppresses constitutive activation of non-canonical NF-kappa-B signaling. The target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, RIPK3, RIPK4, CASP3, CASP7, CASP8, IKBKE, TRAF1, and BCL10. Acts as an important regulator of innate immune signaling via regulation of Toll-like receptors (TLRs), Nodlike receptors (NLRs) and RIG-I like receptors (RLRs), collectively referred to as pattern recognition receptors (PRRs). Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, mitogenic kinase signaling and cell proliferation, as well as cell invasion and metastasis.
• KEGG Pathway:
  NF-kappa B signaling pathway (hsa04064)
  Ubiquitin mediated proteolysis (hsa04120)
  Apoptosis (hsa04210)
  Focal adhesion (hsa04510)
  NOD-like receptor signaling pathway (hsa04621)
  TNF signaling pathway (hsa04668)
  Toxoplasmosis (hsa05145)
  Pathways in cancer (hsa05200)
  Transcriptional misregulation in cancer (hsa05202)
  Small cell lung cancer (hsa05222)
• Reactome Pathway:
  RIPK1-mediated regulated necrosis (R-HSA-5213460)
  Regulation of TNFR1 signaling (R-HSA-5357905)
  TNFR1-induced NFkappaB signaling pathway (R-HSA-5357956)
  TNFR2 non-canonical NF-kB pathway (R-HSA-5668541)
  Regulation of necroptotic cell death (R-HSA-5675482)
  TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway (R-HSA-5676594)
  IKK complex recruitment mediated by RIP1 (R-HSA-937041)
  NOD1/2 Signaling Pathway (R-HSA-168638)

Molecular Interaction Atlas (MIA) of This DTT

9 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
ISIS 23412	DMJ0LB1	Discovery agent	N.A.	Investigative	[1]
ISIS 23414	DMOC0DT	Discovery agent	N.A.	Investigative	[1]
ISIS 23416	DMHQD76	Discovery agent	N.A.	Investigative	[1]
ISIS 23452	DM17G39	Discovery agent	N.A.	Investigative	[1]
ISIS 23454	DM7FPZV	Discovery agent	N.A.	Investigative	[1]
ISIS 23459	DM4PGRU	Discovery agent	N.A.	Investigative	[1]
SM-122	DMC7YQE	Discovery agent	N.A.	Investigative	[2]
SM-131	DMP8VO6	Discovery agent	N.A.	Investigative	[3]
SM-337	DMOSTP9	Discovery agent	N.A.	Investigative	[2]

References

• [1] US patent application no. 5,958,771, Antisense modulation of cellular inhibitor of Apoptosis-2 expression.
• [2] Nonpeptidic and potent small-molecule inhibitors of cIAP-1/2 and XIAP proteins. J Med Chem. 2010 Sep 9;53(17):6361-7.
• [3] Design, synthesis, and evaluation of tricyclic, conformationally constrained small-molecule mimetics of second mitochondria-derived activator of ca... J Med Chem. 2008 Dec 11;51(23):7352-5.