Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTR7B60)

DTT Name X-linked inhibitor of apoptosis protein (XIAP)
Synonyms
hILP; hIAP3; hIAP-3; Xlinked IAP; X-linked IAP; RING-type E3 ubiquitin transferase XIAP; Inhibitor of apoptosis protein 3; ILP; IAPlike protein; IAP3; IAP-like protein; IAP-3; E3 ubiquitinprotein ligase XIAP; E3 ubiquitin-protein ligase XIAP; Baculoviral IAP repeatcontaining protein 4; Baculoviral IAP repeat-containing protein 4; BIRC4; API3
Gene Name XIAP
DTT Type
Clinical trial target
 [1]
BioChemical Class
Acyltransferase
UniProt ID
XIAP_HUMAN
TTD ID
T16769
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
MTFNSFEGSKTCVPADINKEEEFVEEFNRLKTFANFPSGSPVSASTLARAGFLYTGEGDT
VRCFSCHAAVDRWQYGDSAVGRHRKVSPNCRFINGFYLENSATQSTNSGIQNGQYKVENY
LGSRDHFALDRPSETHADYLLRTGQVVDISDTIYPRNPAMYSEEARLKSFQNWPDYAHLT
PRELASAGLYYTGIGDQVQCFCCGGKLKNWEPCDRAWSEHRRHFPNCFFVLGRNLNIRSE
SDAVSSDRNFPNSTNLPRNPSMADYEARIFTFGTWIYSVNKEQLARAGFYALGEGDKVKC
FHCGGGLTDWKPSEDPWEQHAKWYPGCKYLLEQKGQEYINNIHLTHSLEECLVRTTEKTP
SLTRRIDDTIFQNPMVQEAIRMGFSFKDIKKIMEEKIQISGSNYKSLEVLVADLVNAQKD
SMQDESSQTSLQKEISTEEQLRRLQEEKLCKICMDRNIAIVFVPCGHLVTCKQCAEAVDK
CPMCYTVITFKQKIFMS
Function
Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, CASP3, CASP7, CASP8, CASP9, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS and BIRC5/survivin. Ubiquitinion of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitinion of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinationg COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Acts as an important regulator of innate immune signaling via regulation of Nodlike receptors (NLRs). 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. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program. Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, 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 )
Toxoplasmosis (hsa05145 )
HTLV-I infection (hsa05166 )
Pathways in cancer (hsa05200 )
Small cell lung cancer (hsa05222 )
Reactome Pathway
SMAC-mediated dissociation of IAP (R-HSA-111464 )
Deactivation of the beta-catenin transactivating complex (R-HSA-3769402 )
RIPK1-mediated regulated necrosis (R-HSA-5213460 )
Regulation of TNFR1 signaling (R-HSA-5357905 )
TNFR1-induced NFkappaB signaling pathway (R-HSA-5357956 )
Regulation of necroptotic cell death (R-HSA-5675482 )
SMAC binds to IAPs (R-HSA-111463 )

Molecular Interaction Atlas (MIA) of This DTT

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DTT
6 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]
Phenoxodiol DMBUJVX Ovarian cancer 2C73 Phase 1/2 [3]
APG-1387 DMLEKUY Haematological malignancy 2B33.Y Phase 1 [4]
GDC-0152 DM1B3UM Obesity 5B81 Phase 1 [5]
HGS-1029 DMS9WXG Haematological malignancy 2B33.Y Phase 1 [6]
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⏷ Show the Full List of 6 Clinical Trial Drug(s)
34 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 [7]
PMID25980951-Compound-10 DME3ZJO N. A. N. A. Patented [7]
PMID25980951-Compound-11 DMZ9LSY N. A. N. A. Patented [7]
PMID25980951-Compound-12 DMG8K1P N. A. N. A. Patented [7]
PMID25980951-Compound-13 DMGHR4D N. A. N. A. Patented [7]
PMID25980951-Compound-14 DM637IC N. A. N. A. Patented [7]
PMID25980951-Compound-15 DMB2MIT N. A. N. A. Patented [7]
PMID25980951-Compound-19 DMGIV0M N. A. N. A. Patented [7]
PMID25980951-Compound-20 DMM45AC N. A. N. A. Patented [7]
PMID25980951-Compound-21 DMIE0MR N. A. N. A. Patented [7]
PMID25980951-Compound-22 DM6OEHK N. A. N. A. Patented [7]
PMID25980951-Compound-26 DMK9DH7 N. A. N. A. Patented [7]
PMID25980951-Compound-27 DMXAH9F N. A. N. A. Patented [7]
PMID25980951-Compound-28 DMV0EIA N. A. N. A. Patented [7]
PMID25980951-Compound-29 DM5WIX3 N. A. N. A. Patented [7]
PMID25980951-Compound-3 DMPSWXU N. A. N. A. Patented [7]
PMID25980951-Compound-30 DMXCSHE N. A. N. A. Patented [7]
PMID25980951-Compound-31 DMC1Y2T N. A. N. A. Patented [7]
PMID25980951-Compound-32 DMXETA8 N. A. N. A. Patented [7]
PMID25980951-Compound-33 DMYO9UD N. A. N. A. Patented [7]
PMID25980951-Compound-36 DMBD4K9 N. A. N. A. Patented [7]
PMID25980951-Compound-37 DMHP6J2 N. A. N. A. Patented [7]
PMID25980951-Compound-38 DMEUBDA N. A. N. A. Patented [7]
PMID25980951-Compound-39 DMEZ3QV N. A. N. A. Patented [7]
PMID25980951-Compound-4 DM9RZSH N. A. N. A. Patented [7]
PMID25980951-Compound-40 DMJOD8I N. A. N. A. Patented [7]
PMID25980951-Compound-41 DMNROIP N. A. N. A. Patented [7]
PMID25980951-Compound-42 DM8XESD N. A. N. A. Patented [7]
PMID25980951-Compound-43 DMTJRCS N. A. N. A. Patented [7]
PMID25980951-Compound-44 DMS5896 N. A. N. A. Patented [7]
PMID25980951-Compound-45 DM1EU06 N. A. N. A. Patented [7]
PMID25980951-Compound-5 DMB3IZT N. A. N. A. Patented [7]
PMID25980951-Compound-6 DMVSW5N N. A. N. A. Patented [7]
PMID25980951-Compound-7 DMF8V5J N. A. N. A. Patented [7]
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⏷ Show the Full List of 34 Patented Agent(s)

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 Interpreting expression profiles of cancers by genome-wide survey of breadth of expression in normal tissues. Genomics 2005 Aug;86(2):127-41.
4 XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells.Theranostics. 2018 Feb 5;8(6):1494-1510.
5 Discovery of a potent small-molecule antagonist of inhibitor of apoptosis (IAP) proteins and clinical candidate for the treatment of cancer (GDC-0152). J Med Chem. 2012 May 10;55(9):4101-13.
6 Clinical pipeline report, company report or official report of Aegera Therapeutics Inc.
7 Small molecule inhibitor of apoptosis proteins antagonists: a patent review.Expert Opin Ther Pat. 2015 Jul;25(7):755-74.