baculoviral IAP repeat containing 2 | Inhibitors of apoptosis (IAP) protein family | IUPHAR/BPS Guide to PHARMACOLOGY

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baculoviral IAP repeat containing 2

target has curated data in GtoImmuPdb

Target id: 2791

Nomenclature: baculoviral IAP repeat containing 2

Family: Inhibitors of apoptosis (IAP) protein family

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Contents:

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 618 11q22 BIRC2 baculoviral IAP repeat containing 2
Mouse - 612 9 A1 Birc2 baculoviral IAP repeat-containing 2
Rat - 589 8q11 Birc2 baculoviral IAP repeat-containing 2
Previous and Unofficial Names
c-IAP1 | cIAP1 | MIHB | API1
Database Links
CATH/Gene3D 3.30.40.10
ChEMBL Target CHEMBL5462 (Hs)
Ensembl Gene ENSG00000110330 (Hs), ENSMUSG00000057367 (Mm), ENSRNOG00000010602 (Rn)
Entrez Gene 329 (Hs), 11797 (Mm), 60371 (Rn)
Human Protein Atlas ENSG00000110330 (Hs)
KEGG Gene hsa:329 (Hs), mmu:11797 (Mm), rno:60371 (Rn)
OMIM 601712 (Hs)
RefSeq Nucleotide NM_001166 (Hs), NM_007465 (Mm), NM_021752 (Rn)
RefSeq Protein NP_001157 (Hs), NP_031491 (Mm), NP_068520 (Rn)
UniProtKB Q13490 (Hs), Q62210 (Mm)
Wikipedia BIRC2 (Hs)

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BV-6 Hs Inhibition 6.3 – 7.5 pKd 9
⤷ pKd 6.3 – 7.5 (Kd 4.6x10-7 – 2.9x10-8 M) [9]
Description: Assayed using expressed cIAP1 BIR2-BIR3 domain construct
SM-122 Hs Inhibition 9.0 pKi 8
⤷ pKi 9.0 (Ki 1x10-9 M) [8]
LCL161 Hs Inhibition 7.2 pIC50 3
⤷ pIC50 7.2 (IC50 5.8x10-8 M) [3]
Description: Assay uses recombinantly expressed BIR3 domain of cIAP1
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
birinapant Hs Antagonist >9.0 pKd 1
⤷ pKd >9.0 (Kd <1x10-9 M) [1]
SM-337 Hs Antagonist 8.8 pKi 8
⤷ pKi 8.8 (Ki 1.5x10-9 M) [8]
Description: Fluorescence polarization assay using hcIAP-1 BIR3 domain (residues 253-363)
AT-406 Hs Antagonist 8.7 pKi 2
⤷ pKi 8.7 (Ki 1.9x10-9 M) [2]
Description: Competitive inhibition of human cIAP1 BIR3 domain expressed in Escherichia coli.
GDC-0152 Hs Antagonist 7.8 pKi 4
⤷ pKi 7.8 (Ki 1.7x10-8 M) [4]
Description: BIR3 domain of hcIAP1 (BIRC2)
AZD5582 Hs Antagonist 7.8 pIC50 5
⤷ pIC50 7.8 (IC50 1.5x10-8 M) [5]
Antagonist Comments
AZD5582 is a peptide mimetic. It consists of a dimeric structure, with sequences based on the AVPI motif of DIABLO (aka Smac; Q9NR28). DIABLO is a peptide of mitochondrial origin and is an endogenous pro-apoptotic antagonist of IAP protein function.
Immunopharmacology Comments
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [6], and represent novel drug targets in inflammatory processes [7].
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 7 GO processes
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0034121 regulation of toll-like receptor signaling pathway TAS
GO:0035666 TRIF-dependent toll-like receptor signaling pathway TAS
GO:0039535 regulation of RIG-I signaling pathway TAS
GO:0045088 regulation of innate immune response TAS
GO:0050727 regulation of inflammatory response TAS
GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway TAS
Immuno Process:  Immune regulation
GO Annotations:  Associated to 7 GO processes
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0034121 regulation of toll-like receptor signaling pathway TAS
GO:0035666 TRIF-dependent toll-like receptor signaling pathway TAS
GO:0039535 regulation of RIG-I signaling pathway TAS
GO:0045088 regulation of innate immune response TAS
GO:0050727 regulation of inflammatory response TAS
GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway TAS
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 4 GO processes
GO:0010803 regulation of tumor necrosis factor-mediated signaling pathway TAS
GO:0033209 tumor necrosis factor-mediated signaling pathway TAS
GO:0039535 regulation of RIG-I signaling pathway TAS
GO:0071356 cellular response to tumor necrosis factor IGI
Immuno Process:  Cellular signalling
GO Annotations:  Associated to 13 GO processes
GO:0000209 protein polyubiquitination IDA
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS
GO:0004842 ubiquitin-protein transferase activity IDA
GO:0031398 positive regulation of protein ubiquitination IBA
GO:0034121 regulation of toll-like receptor signaling pathway TAS
GO:0035666 TRIF-dependent toll-like receptor signaling pathway TAS
GO:0039535 regulation of RIG-I signaling pathway TAS
GO:0061630 ubiquitin protein ligase activity IBA
GO:0070424 regulation of nucleotide-binding oligomerization domain containing signaling pathway TAS
GO:1902523 positive regulation of protein K63-linked ubiquitination IDA
GO:1902524 positive regulation of protein K48-linked ubiquitination IDA
GO:1902527 positive regulation of protein monoubiquitination IDA
GO:1902916 positive regulation of protein polyubiquitination IGI
Physiological Consequences of Altering Gene Expression
Birc2 and Birc3 null mice are resistant to inflammasome-dependent peritonitis.
Species:  Mouse
Tissue: 
Technique: 
References:  6

References

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1. Allensworth JL, Sauer SJ, Lyerly HK, Morse MA, Devi GR. (2013) Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-α-independent mechanism. Breast Cancer Res. Treat., 137 (2): 359-71. [PMID:23225169]

2. Cai Q, Sun H, Peng Y, Lu J, Nikolovska-Coleska Z, McEachern D, Liu L, Qiu S, Yang CY, Miller R et al.. (2011) A potent and orally active antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in clinical development for cancer treatment. J. Med. Chem., 54 (8): 2714-26. [PMID:21443232]

3. Donnell AF, Michoud C, Rupert KC, Han X, Aguilar D, Frank KB, Fretland AJ, Gao L, Goggin B, Hogg JH et al.. (2013) Benzazepinones and benzoxazepinones as antagonists of inhibitor of apoptosis proteins (IAPs) selective for the second baculovirus IAP repeat (BIR2) domain. J. Med. Chem., 56 (20): 7772-87. [PMID:24083782]

4. Flygare JA, Beresini M, Budha N, Chan H, Chan IT, Cheeti S, Cohen F, Deshayes K, Doerner K, Eckhardt SG et al.. (2012) 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., 55 (9): 4101-13. [PMID:22413863]

5. Hennessy EJ, Adam A, Aquila BM, Castriotta LM, Cook D, Hattersley M, Hird AW, Huntington C, Kamhi VM, Laing NM et al.. (2013) 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., 56 (24): 9897-919. [PMID:24320998]

6. Labbé K, McIntire CR, Doiron K, Leblanc PM, Saleh M. (2011) Cellular inhibitors of apoptosis proteins cIAP1 and cIAP2 are required for efficient caspase-1 activation by the inflammasome. Immunity, 35 (6): 897-907. [PMID:22195745]

7. Mayer BA, Rehberg M, Erhardt A, Wolf A, Reichel CA, Kracht M, Krombach F, Tiegs G, Zahler S, Vollmar AM et al.. (2011) Inhibitor of apoptosis proteins as novel targets in inflammatory processes. Arterioscler. Thromb. Vasc. Biol., 31 (10): 2240-50. [PMID:21817100]

8. Peng Y, Sun H, Nikolovska-Coleska Z, Qiu S, Yang CY, Lu J, Cai Q, Yi H, Kang S, Yang D et al.. (2008) Potent, orally bioavailable diazabicyclic small-molecule mimetics of second mitochondria-derived activator of caspases. J. Med. Chem., 51 (24): 8158-62. [PMID:19049347]

9. Varfolomeev E, Blankenship JW, Wayson SM, Fedorova AV, Kayagaki N, Garg P, Zobel K, Dynek JN, Elliott LO, Wallweber HJ et al.. (2007) IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell, 131 (4): 669-81. [PMID:18022362]

How to cite this page

Inhibitors of apoptosis (IAP) protein family: baculoviral IAP repeat containing 2. Last modified on 15/02/2017. Accessed on 13/12/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2791.