Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTIRY6K)

• DTT Name: Cellular inhibitor of apoptosis 2 (BIRC3)
• Synonyms: hIAP1; hIAP-1; TNFR2TRAFsignaling complex protein 1; TNFR2-TRAF-signaling complex protein 1; RNF49; RING-type E3 ubiquitin transferase BIRC3; RING finger protein 49; MIHC; Inhibitor of apoptosis protein 1; IAP1; IAP homolog C; CIAP2; C-IAP2; Baculoviral IAP repeatcontaining protein3; Baculoviral IAP repeat-containing protein 3; Apoptosis inhibitor 2; API2
• Gene Name: BIRC3
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Acyltransferase
• UniProt ID: BIRC3_HUMAN
• TTD ID: T35173
• 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

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AT-406	DMVJW0S	Squamous head and neck cell carcinom	2D60.0	Phase 3	[1]

4 Patented Agent(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PMID25980951-Compound-1	DMYPT2H	N. A.	N. A.	Patented	[2]
PMID25980951-Compound-27	DMXAH9F	N. A.	N. A.	Patented	[2]
PMID25980951-Compound-43	DMTJRCS	N. A.	N. A.	Patented	[2]
PMID25980951-Compound-44	DMS5896	N. A.	N. A.	Patented	[2]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
AZD5582	DMPIHN6	Discovery agent	N.A.	Investigative	[3]

References

• [1] Debio 1143, an antagonist of multiple inhibitor-of-apoptosis proteins, activates apoptosis and enhances radiosensitization of non-small cell lung c... Am J Cancer Res. 2014 Nov 19;4(6):943-51.
• [2] Small molecule inhibitor of apoptosis proteins antagonists: a patent review.Expert Opin Ther Pat. 2015 Jul;25(7):755-74.
• [3] Discovery of a novel class of dimeric Smac mimetics as potent IAP antagonists resulting in a clinical candidate for the treatment of cancer (AZD5582). J Med Chem. 2013 Dec 27;56(24):9897-919.