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baculoviral IAP repeat containing 2

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 2791

Nomenclature: baculoviral IAP repeat containing 2

Family: Inhibitors of apoptosis (IAP) protein family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 618 11q22.2 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 Click here for help
API1 | c-IAP1 | cIAP1 | MIHB
Database Links Click here for help
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BV-6 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Inhibition 6.3 – 7.5 pKd 11
pKd 6.3 – 7.5 (Kd 4.6x10-7 – 2.9x10-8 M) [11]
Description: Assayed using expressed cIAP1 BIR2-BIR3 domain construct
SM-122 Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.0 pKi 10
pKi 9.0 (Ki 1x10-9 M) [10]
tolinapant Small molecule or natural product Click here for species-specific activity table Hs Inhibition 9.7 pIC50 6
pIC50 9.7 (IC50 2.2x10-10 M) [6]
Description: Measuring inhibition of intracellular degradation of cIAP1 in MDA-MB-231 cells
LCL161 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure 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 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist >9.0 pKd 1
pKd >9.0 (Kd <1x10-9 M) [1]
SM-337 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.8 pKi 10
pKi 8.8 (Ki 1.5x10-9 M) [10]
Description: Fluorescence polarization assay using hcIAP-1 BIR3 domain (residues 253-363)
xevinapant Small molecule or natural product Primary target of this compound Click here for species-specific activity table 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 Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.8 pKi 4
pKi 7.8 (Ki 1.7x10-8 M) [4]
Description: BIR3 domain of hcIAP1 (BIRC2)
AZD5582 Small molecule or natural product Primary target of this compound Click here for species-specific activity table 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.
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 20 [PMID: 34432979] Small molecule or natural product Click here for species-specific activity table Hs Binding 7.1 pIC50 9
pIC50 7.1 (IC50 7.94x10-8 M) [9]
Description: Binding to the BIR3 domain of hcIAP1, determined in a fluorescence polarisation assay.
Immunopharmacology Comments
Cellular inhibitors of apoptosis proteins BIRC2 and BIRC3 are required for efficient caspase-1 activation by the inflammasome [7], and represent novel drug targets in inflammatory processes [8].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Physiological Consequences of Altering Gene Expression Click here for help
Birc2 and Birc3 null mice are resistant to inflammasome-dependent peritonitis.
Species:  Mouse
Tissue: 
Technique: 
References:  7

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. Johnson CN, Ahn JS, Buck IM, Chiarparin E, Day JEH, Hopkins A, Howard S, Lewis EJ, Martins V, Millemaggi A et al.. (2018) A Fragment-Derived Clinical Candidate for Antagonism of X-Linked and Cellular Inhibitor of Apoptosis Proteins: 1-(6-[(4-Fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-1 H,2 H,3 H-pyrrolo[3,2- b]pyridin-1-yl)-2-[(2 R,5 R)-5-methyl-2-([(3R)-3-methylmorpholin-4-yl]methyl)piperazin-1-yl]ethan-1-one (ASTX660). J Med Chem, 61 (16): 7314-7329. [PMID:30091600]

7. 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]

8. 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]

9. Miah AH, Smith IED, Rackham M, Mares A, Thawani AR, Nagilla R, Haile PA, Votta BJ, Gordon LJ, Watt G et al.. (2021) Optimization of a Series of RIPK2 PROTACs. J Med Chem, 64 (17): 12978-13003. [PMID:34432979]

10. 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]

11. 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 05/06/2023. Accessed on 02/12/2023. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2791.