Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTQ5LRD)

DTT Name Cellular inhibitor of apoptosis 1 (BIRC2)
Synonyms
hIAP2; hIAP-2; TNFR2TRAFsignaling complex protein 2; TNFR2-TRAF-signaling complex protein 2; RNF48; RING-type E3 ubiquitin transferase BIRC2; RING finger protein 48; MIHB; Inhibitor of apoptosis protein 2; IAP2; IAP homolog B; CIAP1; C-IAP1; Baculoviral IAP repeatcontaining protein 2; Baculoviral IAP repeat-containing protein 2; API1
Gene Name BIRC2
DTT Type
Clinical trial target
 [1]
BioChemical Class
Acyltransferase
UniProt ID
BIRC2_HUMAN
TTD ID
T84780
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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EC Number
EC 2.3.2.27
Sequence
MHKTASQRLFPGPSYQNIKSIMEDSTILSDWTNSNKQKMKYDFSCELYRMSTYSTFPAGV
PVSERSLARAGFYYTGVNDKVKCFCCGLMLDNWKLGDSPIQKHKQLYPSCSFIQNLVSAS
LGSTSKNTSPMRNSFAHSLSPTLEHSSLFSGSYSSLSPNPLNSRAVEDISSSRTNPYSYA
MSTEEARFLTYHMWPLTFLSPSELARAGFYYIGPGDRVACFACGGKLSNWEPKDDAMSEH
RRHFPNCPFLENSLETLRFSISNLSMQTHAARMRTFMYWPSSVPVQPEQLASAGFYYVGR
NDDVKCFCCDGGLRCWESGDDPWVEHAKWFPRCEFLIRMKGQEFVDEIQGRYPHLLEQLL
STSDTTGEENADPPIIHFGPGESSSEDAVMMNTPVVKSALEMGFNRDLVKQTVQSKILTT
GENYKTVNDIVSALLNAEDEKREEEKEKQAEEMASDDLSLIRKNRMALFQQLTCVLPILD
NLLKANVINKQEHDIIKQKTQIPLQARELIDTILVKGNAAANIFKNCLKEIDSTLYKNLF
VDKNMKYIPTEDVSGLSLEEQLRRLQEERTCKVCMDKEVSVVFIPCGHLVVCQECAPSLR
KCPICRGIIKGTVRTFLS
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, TRAF2, DIABLO/SMAC, MAP3K14/NIK, MAP3K5/ASK1, IKBKG/NEMO, IKBKE and MXD1/MAD1. Can also function as an E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. 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. Can stimulate the transcriptional activity of E2F1. Plays a role in the modulation of the cell cycle. 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 )
Hippo signaling pathway (hsa04390 )
Focal adhesion (hsa04510 )
NOD-like receptor signaling pathway (hsa04621 )
TNF signaling pathway (hsa04668 )
Toxoplasmosis (hsa05145 )
Pathways in cancer (hsa05200 )
Small cell lung cancer (hsa05222 )
Reactome Pathway
NOD1/2 Signaling Pathway (R-HSA-168638 )
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 )
Apoptotic cleavage of cellular proteins (R-HSA-111465 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
2 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 [2]
Birinapant DM6PBUM Lymphoma 2A80-2A86 Phase 2 [1]
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21 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 [3]
PMID25980951-Compound-16 DM1J3LE N. A. N. A. Patented [3]
PMID25980951-Compound-17 DMSC8B6 N. A. N. A. Patented [3]
PMID25980951-Compound-18 DMC3NHJ N. A. N. A. Patented [3]
PMID25980951-Compound-19 DMGIV0M N. A. N. A. Patented [3]
PMID25980951-Compound-20 DMM45AC N. A. N. A. Patented [3]
PMID25980951-Compound-21 DMIE0MR N. A. N. A. Patented [3]
PMID25980951-Compound-22 DM6OEHK N. A. N. A. Patented [3]
PMID25980951-Compound-27 DMXAH9F N. A. N. A. Patented [3]
PMID25980951-Compound-3 DMPSWXU N. A. N. A. Patented [3]
PMID25980951-Compound-36 DMBD4K9 N. A. N. A. Patented [3]
PMID25980951-Compound-37 DMHP6J2 N. A. N. A. Patented [3]
PMID25980951-Compound-38 DMEUBDA N. A. N. A. Patented [3]
PMID25980951-Compound-4 DM9RZSH N. A. N. A. Patented [3]
PMID25980951-Compound-41 DMNROIP N. A. N. A. Patented [3]
PMID25980951-Compound-42 DM8XESD N. A. N. A. Patented [3]
PMID25980951-Compound-43 DMTJRCS N. A. N. A. Patented [3]
PMID25980951-Compound-44 DMS5896 N. A. N. A. Patented [3]
PMID25980951-Compound-5 DMB3IZT N. A. N. A. Patented [3]
PMID25980951-Compound-6 DMVSW5N N. A. N. A. Patented [3]
PMID25980951-Compound-7 DMF8V5J N. A. N. A. Patented [3]
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⏷ Show the Full List of 21 Patented Agent(s)
3 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
AZD5582 DMPIHN6 Discovery agent N.A. Investigative [4]
BV-6 DMDTV7A Discovery agent N.A. Investigative [5]
EAPB0203 DMB7685 T-cell leukaemia 2A90 Investigative [6]
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References

1 cIAPs and XIAP regulate myelopoiesis through cytokine production in an RIPK1- and RIPK3-dependent manner. Blood. 2014 Apr 17;123(16):2562-72.
2 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.
3 Small molecule inhibitor of apoptosis proteins antagonists: a patent review.Expert Opin Ther Pat. 2015 Jul;25(7):755-74.
4 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.
5 IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell. 2007 Nov 16;131(4):669-81.
6 EAPB0203, a member of the imidazoquinoxaline family, inhibits growth and induces caspase-dependent apoptosis in T-cell lymphomas and HTLV-I-associated adult T-cell leukemia/lymphoma. Blood. 2008 Apr 1;111(7):3770-7.