baculoviral IAP repeat containing 2

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

   GtoImmuPdb view: OFF :     baculoviral IAP repeat containing 2 has curated GtoImmuPdb data

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
ChEMBL Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

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 Affinity Units 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 Affinity Units 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
Immuno Process ID:  2
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of toll-like receptor signaling pathway (GO:0034121) TAS
TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
regulation of innate immune response (GO:0045088) TAS
regulation of inflammatory response (GO:0050727) TAS
regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
References: 
Immuno Process:  Immune regulation
Immuno Process ID:  6
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of toll-like receptor signaling pathway (GO:0034121) TAS
TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
regulation of innate immune response (GO:0045088) TAS
regulation of inflammatory response (GO:0050727) TAS
regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
References: 
Immuno Process:  Cytokine production & signalling
Immuno Process ID:  9
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  regulation of tumor necrosis factor-mediated signaling pathway (GO:0010803) TAS
tumor necrosis factor-mediated signaling pathway (GO:0033209) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
References: 
Immuno Process:  Cellular signalling
Immuno Process ID:  11
Comment: 
GO Annotation:  Associated to GO processes
GO Processes:  protein polyubiquitination (GO:0000209) IDA
ubiquitin-protein transferase activity (GO:0004842) IDA
regulation of toll-like receptor signaling pathway (GO:0034121) TAS
TRIF-dependent toll-like receptor signaling pathway (GO:0035666) TAS
regulation of RIG-I signaling pathway (GO:0039535) TAS
proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) IDA
regulation of nucleotide-binding oligomerization domain containing signaling pathway (GO:0070424) TAS
positive regulation of protein K63-linked ubiquitination (GO:1902523) IDA
positive regulation of protein K48-linked ubiquitination (GO:1902524) IDA
positive regulation of protein monoubiquitination (GO:1902527) IDA
References: 
Physiological Consequences of Altering Gene Expression
Birc2 and Birc3 null mice are resistant to inflammasome-dependent peritonitis.
Species:  Mouse
Tissue: 
Technique: 
References:  6

References

Show »

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. Immunity35 (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. Cell131 (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 20/10/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2791.