BIRC3

Summary

BIRC3 (baculoviral IAP repeat containing 3, HGNC:591) is a protein-coding gene on chromosome 11q22.2, encoding Baculoviral IAP repeat-containing protein 3 (Q13489). 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.

This gene encodes a member of the IAP family of proteins that inhibit apoptosis by binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2, probably by interfering with activation of ICE-like proteases. The encoded protein inhibits apoptosis induced by serum deprivation but does not affect apoptosis resulting from exposure to menadione, a potent inducer of free radicals. It contains 3 baculovirus IAP repeats and a ring finger domain. Transcript variants encoding the same isoform have been identified.

Source: NCBI Gene 330 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 80 total — 1 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 17
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_001165

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:591
Approved symbol	BIRC3
Name	baculoviral IAP repeat containing 3
Location	11q22.2
Locus type	gene with protein product
Status	Approved
Aliases	cIAP2, hiap-1, MIHC, RNF49, MALT2, c-IAP2
Ensembl gene	ENSG00000023445
Ensembl biotype	protein_coding
OMIM	601721
Entrez	330

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000263464, ENST00000526421, ENST00000527309, ENST00000527336, ENST00000528940, ENST00000532808, ENST00000673846, ENST00000953525

RefSeq mRNA: 2 — MANE Select: NM_001165 NM_001165, NM_182962

CCDS: CCDS8315

Canonical transcript exons

ENST00000263464 — 9 exons

Exon	Start	End
ENSE00000745287	102328052	102328130
ENSE00000745300	102335966	102336220
ENSE00000795265	102328897	102328945
ENSE00000795266	102330999	102331241
ENSE00001256551	102321837	102325362
ENSE00002467460	102336760	102336801
ENSE00002474565	102325466	102325565
ENSE00003901412	102336909	102339403
ENSE00003903075	102317484	102317571

Expression profiles

Bgee: expression breadth ubiquitous, 238 present calls, max score 97.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6796 / max 867.4897, expressed in 969 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116399	16.9853	897
116401	2.7738	447
116400	1.2233	336
116404	0.6380	198
116402	0.4982	196
116403	0.2422	73
116406	0.1317	61
116405	0.0952	42
116407	0.0920	43

Top tissues by expression

281 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
vermiform appendix	UBERON:0001154	97.33	gold quality
epithelium of nasopharynx	UBERON:0001951	96.57	gold quality
nasopharynx	UBERON:0001728	96.56	gold quality
cartilage tissue	UBERON:0002418	96.16	gold quality
lymph node	UBERON:0000029	95.74	gold quality
spleen	UBERON:0002106	94.03	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.73	gold quality
gall bladder	UBERON:0002110	92.55	gold quality
granulocyte	CL:0000094	92.31	gold quality
caecum	UBERON:0001153	91.75	gold quality
small intestine	UBERON:0002108	91.36	gold quality
mucosa of sigmoid colon	UBERON:0004993	90.77	gold quality
colonic mucosa	UBERON:0000317	90.69	gold quality
palpebral conjunctiva	UBERON:0001812	90.33	gold quality
tonsil	UBERON:0002372	90.32	gold quality
rectum	UBERON:0001052	90.13	gold quality
superficial temporal artery	UBERON:0001614	89.95	gold quality
colonic epithelium	UBERON:0000397	89.91	gold quality
calcaneal tendon	UBERON:0003701	89.67	gold quality
body of stomach	UBERON:0001161	89.49	gold quality
islet of Langerhans	UBERON:0000006	89.41	gold quality
ileal mucosa	UBERON:0000331	88.85	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.78	gold quality
bone marrow cell	CL:0002092	88.59	gold quality
intestine	UBERON:0000160	87.86	gold quality
epithelial cell of pancreas	CL:0000083	87.74	gold quality
mucosa of transverse colon	UBERON:0004991	87.72	gold quality
upper lobe of left lung	UBERON:0008952	87.50	gold quality
blood	UBERON:0000178	87.46	gold quality
nerve	UBERON:0001021	87.44	gold quality

Single-cell (SCXA)

Detected in 29 experiment(s), a significant marker in 24.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	12847.32
E-CURD-46	yes	4502.75
E-CURD-79	yes	3898.45
E-MTAB-7381	yes	3542.54
E-MTAB-6653	yes	2885.77
E-GEOD-139324	yes	2062.64
E-MTAB-8530	yes	1998.62
E-HCAD-8	yes	1727.01
E-MTAB-8207	yes	1550.12
E-MTAB-10885	yes	1100.81
E-MTAB-10855	yes	769.46
E-HCAD-4	yes	140.49
E-HCAD-1	yes	115.75
E-MTAB-8142	yes	84.98
E-GEOD-125970	yes	63.38

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CREB1, DAXX, DEK, ESR1, ETS1, ETS2, FOXA2, FOXO1, FOXP3, GLI1, HDAC1, HIF1A, IRF1, JUN, KAT7, KLF4, LHX2, NFKB1, NFKB, NFKBIA, NR4A3, PARP1, PAX1, REL, RELA, RELB, STAT3, TP53, ZNF804A

miRNA regulators (miRDB)

93 targeting BIRC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-374A-5P	99.90	71.34	2923
HSA-MIR-374B-5P	99.90	69.98	2734
HSA-MIR-4493	99.90	66.48	977
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-369-3P	99.85	70.52	2264
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909

Literature-anchored findings (GeneRIF, showing 40)

• REVIEW: Genetic alterations involving API2 underlying the pathogenesis of MALT lymphoma (PMID:11960389)
• promotes tumor cell survival in mesothelioma (PMID:12082024)
• Interferon-beta therapy exerts a regulatory effect on peripheral T lymphocytes through an anti-apoptosis mechanism that involves the downregulation of cellular Inhibitor of Apoptosis Protein expression. (PMID:12161039)
• These results indicate that IAPs alone are not the main factor responsible for the resistance of non-small-cell lung cancer cells to treatment. (PMID:12243753)
• pathway and antiapoptotic effect of up-regulation of cIAP2 by G-CSF in neutrophils, and overexpression of cIAP2 in chronic neutrophilic leukemia (PMID:12393423)
• Cellular inhibitors of apoptosis 1 and 2 are ubiquitin ligases for the apoptosis inducer Smac/DIABLO. (PMID:12525502)
• Fuses with MALT1 and defines a distinctive clinicopathologic subtype in pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue. (PMID:12651604)
• cIAP1 and cIAP2 are potential oncogenes and are overexpressed in multiple lung cancers with or without higher copy numbers (PMID:12651874)
• these results indicate that unlike Smac/DIABLO, Omi/HtrA2’s catalytic cleavage of IAPs is a key mechanism for it to irreversibly inactivate IAPs and promote apoptosis. (PMID:12815069)
• cIAP-2 is an important regulator of apoptosis in bladder cancer and its overexpression may make tumours less susceptible to therapy involving apoptosis. (PMID:12926068)
• overexpression of PKC delta induced cIAP-2 promoter activity and increased NF-kappa B transactivation, suggesting regulation of cIAP-2 expression by a PKC delta/NF-kappa B pathway (PMID:14527959)
• copy numbers of API2-MALT1 do not reflect tumor cell proportions, and that the number of copies of API2-MALT1 in a tumor cell is different for each clinical sample. (PMID:14562112)
• Relative risk of death was lower for cytoplasmic c-IAP1, cytoplasmic c-IAP2, and nuclear c-IAP2 expression. It was higher for nuclear c-IAP1 expression. (PMID:14708638)
• levels of c-IAP1 and c-IAP2 are regulated by Smac/DIABLO through the ubiquitin/proteasome pathway (PMID:14960576)
• PR39 causes an increase in gene expression from a transfected human cDNA IAP-2 promoter in BAEC cells. PR39-induced increase in the level of IAP-2 mRNA in BAECs is due to an increase in transcription rate and mRNA stability. (PMID:15023888)
• decreased cIAP2 may play a role in increased apoptosis in aged humans (PMID:15037009)
• cAMP can induce c-IAP2 expression in colon cancer cells through CREB phosphorylation and CRE-dependent transcription in a manner that involves activation of ERK1/2 and p38 MAPK (PMID:15078890)
• X-linked XIAP is present in Chronic lymphocytic leukemia cells and is up-regulated in conditions where apoptosis is prevented. (PMID:15183896)
• Detection of API2-MALT1 fusion transcripts is useful for evaluating the prognosis and clinical behavior of the MALT lymphoma. (PMID:15363040)
• NF-kappa B signaling, once activated in a CD40-dependent immune response, is maintained and enhanced through deregulation of MALT1 or formation of an API2-MALT1 fusion (PMID:15598810)
• API2-MALT1 transcript was confirmed to be associated with the levels of apoptosis and API2 of MALT lymphoma. (PMID:15696476)
• cIAP2 expression is up-regulated by IFN-alpha and IFN-gamma through the JAK2-STAT3 pathway, and increased expression of the cIAP2 protein may contribute to an IFN-alpha- and IFN-gamma-mediated antiapoptotic effect on human neutrophils. (PMID:15845643)
• Upregulation of c-IAP2 by E6 and E7 may confer resistance to apoptosis that is necessary for sustained growth of some HPV16- and HPV18-positive cancer cells. (PMID:15856013)
• Taken together, our results strongly indicated that API2-MALT1 possesses a novel mechanism of self-activation by up-regulating its own expression in t(11;18)(q21;q21)-carrying MALT lymphomas. (PMID:15982633)
• IAP-2, XIAP, and survivin may make an important contribution to the resistance to the apoptotic effect of cisplatin in prostate cancer (PMID:16142363)
• cIAP1 and cIAP2 bind but do not inhibit caspases (PMID:16339151)
• demonstrates, for the first time, that BIRC3 (anti-apoptotic protein), COL3A1 (matrix protein synthesis), and CXCL3 (chemokine) were up-regulated in the thrombin-stimulated human umbilical vein endothelial cells (PMID:16356540)
• Common translocation in MALT lymphoma results in a fusion of the cIAP2 region on chromosome 11q21 with the MALT1 gene on chromosome 18q21. (PMID:16395399)
• cIAP2 is an inhibitor of antigenic signaling and implicate its dysfunction in MALT lymphomas. (PMID:16395405)
• Tax-mediated HIAP-1 overexpression is required to suppress endogenous apoptosis and, therefore, is essential for the survival of HTLV-1-transformed lymphocytes (PMID:16467195)
• Eosinophils of hypereosinophilic syndrome (HES) patients (but not normal eosinophils) express high levels of cellular IAP-2 (cIAP-2) and inhibit the caspase cascade in HES eosinophils. (PMID:16761316)
• results reveal a physiological function of cIAP2, identify Bcl10 upregulation as a unifying molecular mechanism for MALT lymphomas, and define the mechanism and effects of this upregulation in t(11;18)-positive mucosa-associated lymphoid tissue lymphomas (PMID:16775419)
• Detachment-induced upregulation of XIAP and cIAP2 delays anoikis of intestinal epithelial cells. (PMID:16799641)
• Cell cycle-dependent G2/M-phase-specific cIAP2 expression is enhanced by NF-kappaB activation, and selective down-regulation of cIAP2 causes cells blocked in mitosis with nocodazole to become susceptible to apoptosis. (PMID:16813569)
• the t(11, 18)(q21;q21) translocation creating the c-IAP2.MALT1 fusion protein activates NF-kappaB independently of TRAF1 AND TRAF2 and contributes to human malignancy in the absence of signaling adaptors that might otherwise regulate its activity (PMID:16891304)
• Differential expression of IAPs in B-cell lymphomas suggests differences in pathogenesis that may have implications for novel treatment strategies targeting IAPs. (PMID:16983704)
• Persistent infection of epithelial cell line with Chlamydophila pneumoniae resulted in the upregulation of the NF-kappaB regulated inhibitor of apoptosis protein 2 but not inhibitor of apoptosis protein 1 and apoptosis resistance. (PMID:16984419)
• In particular, the stability of cIAP-2 is modulated by the presence of X-linked IAP and their interaction is stabilized in infected cells. (PMID:17069460)
• TNF-alpha induced expression of c-IAP1 and c-IAP2 via MAP kinases, but not via NF-kappaB, and that MAP kinases participated in the inhibition of apoptosis by induction of c-IAPs in TNF-alpha-stimulated endothelial cells (PMID:17133355)
• Trp323 of BIR3 plays a pivotal role both in maintaining necessary conformation for caspase-9 interaction and to a lesser extent, recognition of Smac-type peptide. (PMID:17179183)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	birc2	ENSDARG00000044619
mus_musculus	Birc3	ENSMUSG00000032000
rattus_norvegicus	Birc3	ENSRNOG00000005731
drosophila_melanogaster	Diap2	FBGN0015247
caenorhabditis_elegans		WBGENE00000250

Paralogs (7): BIRC5 (ENSG00000089685), NLRC4 (ENSG00000091106), BIRC7 (ENSG00000101197), XIAP (ENSG00000101966), BIRC2 (ENSG00000110330), BIRC6 (ENSG00000115760), NAIP (ENSG00000249437)

Protein

Protein identifiers

Baculoviral IAP repeat-containing protein 3 — Q13489 (reviewed: Q13489)

Alternative names: Apoptosis inhibitor 2, Cellular inhibitor of apoptosis 2, IAP homolog C, Inhibitor of apoptosis protein 1, RING finger protein 49, RING-type E3 ubiquitin transferase BIRC3, TNFR2-TRAF-signaling complex protein 1

All UniProt accessions (3): Q13489, A0A669KBC7, H0YCJ5

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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, IKBKE, TRAF1, and BCL10. 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.

Subunit / interactions. Interacts with PRSS25; interaction inhibits apoptotic suppressor activity. The BIR motifs region interacts with TNF receptor associated factors 1 and 2 (TRAF1 and TRAF2) to form a heteromeric complex, which is then recruited to the tumor necrosis factor receptor 2 (TNFR2). Interaction with TRAF2 is required for ubiquitination of IKBKE, degradation of NFKBIA and activation of NF-kappa-B. Interacts with RIP1, RIP2, RIP3, RIP4 and USP19.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Highly expressed in fetal lung, and kidney. In the adult, expression is mainly seen in lymphoid tissues, including spleen, thymus and peripheral blood lymphocytes.

Post-translational modifications. Auto-ubiquitinated and degraded by the proteasome in apoptotic cells.

Disease relevance. A chromosomal aberration involving BIRC3 is recurrent in low-grade mucosa-associated lymphoid tissue (MALT lymphoma). Translocation t(11;18)(q21;q21) with MALT1. This translocation is found in approximately 50% of cytogenetically abnormal low-grade MALT lymphoma.

Activity regulation. USP19 regulates the stability of BIRC3/c-IAP2 by preventing its ubiquitination.

Similarity. Belongs to the IAP family.

RefSeq proteins (2): NP_001156, NP_892007 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001315	CARD	Domain
IPR001370	BIR_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR048875	BIRC2-3-like_UBA	Domain
IPR050784	IAP	Family

Pfam: PF00619, PF00653, PF13920, PF21290

Enzyme classification (BRENDA):

• EC 2.3.2.27 — RING-type E3 ubiquitin transferase (BRENDA: 28 organisms, 138 substrates, 10 inhibitors, 1 Km, 1 kcat entries)

Substrate kinetics (BRENDA)

1 substrates with measured Km, best-characterized 1. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
[UBE2W]-S-UBIQUITINYL-L-CYSTEINE	0.3014	1

UniProt features (50 total): helix 12, strand 10, sequence conflict 8, turn 6, binding site 4, repeat 3, sequence variant 3, chain 1, site 1, domain 1, zinc finger region 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2UVL	X-RAY DIFFRACTION	1.91
3EB5	X-RAY DIFFRACTION	2
3M0A	X-RAY DIFFRACTION	2.61
3M0D	X-RAY DIFFRACTION	2.8
7NK0	X-RAY DIFFRACTION	3.3
3EB6	X-RAY DIFFRACTION	3.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13489-F1	75.13	0.29

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 442–443 (breakpoint for translocation to form birc3-malt1)

Ligand- & substrate-binding residues (4): 292; 295; 312; 319

Function

Pathways and Gene Ontology

Reactome pathways

28 pathways

ID	Pathway
R-HSA-168638	NOD1/2 Signaling Pathway
R-HSA-168927	TICAM1, RIP1-mediated IKK complex recruitment
R-HSA-5213460	RIPK1-mediated regulated necrosis
R-HSA-5357786	TNFR1-induced proapoptotic signaling
R-HSA-5357905	Regulation of TNFR1 signaling
R-HSA-5357956	TNFR1-induced NF-kappa-B signaling pathway
R-HSA-5668541	TNFR2 non-canonical NF-kB pathway
R-HSA-5675482	Regulation of necroptotic cell death
R-HSA-5676594	TNF receptor superfamily (TNFSF) members mediating non-canonical NF-kB pathway
R-HSA-5689880	Ub-specific processing proteases
R-HSA-937041	IKK complex recruitment mediated by RIP1
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-166016	Toll Like Receptor 4 (TLR4) Cascade
R-HSA-166166	MyD88-independent TLR4 cascade
R-HSA-168164	Toll Like Receptor 3 (TLR3) Cascade
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
R-HSA-168643	Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways
R-HSA-168898	Toll-like Receptor Cascades
R-HSA-392499	Metabolism of proteins
R-HSA-5218859	Regulated Necrosis
R-HSA-5357801	Programmed Cell Death
R-HSA-5688426	Deubiquitination
R-HSA-597592	Post-translational protein modification
R-HSA-73887	Death Receptor Signaling
R-HSA-75893	TNF signaling
R-HSA-937061	TRIF (TICAM1)-mediated TLR4 signaling

MSigDB gene sets: 600 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_DN, REACTOME_IKK_COMPLEX_RECRUITMENT_MEDIATED_BY_RIP1, GSE45365_NK_CELL_VS_BCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, CREL_01, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_INNATE_IMMUNE_SYSTEM, MCLACHLAN_DENTAL_CARIES_UP, REACTOME_NOD1_2_SIGNALING_PATHWAY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, REACTOME_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_NLR_SIGNALING_PATHWAYS, chr11q22, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY

GO Biological Process (19): apoptotic process (GO:0006915), cell surface receptor signaling pathway (GO:0007166), canonical NF-kappaB signal transduction (GO:0007249), spermatogenesis (GO:0007283), positive regulation of protein ubiquitination (GO:0031398), tumor necrosis factor-mediated signaling pathway (GO:0033209), regulation of toll-like receptor signaling pathway (GO:0034121), non-canonical NF-kappaB signal transduction (GO:0038061), regulation of RIG-I signaling pathway (GO:0039535), regulation of apoptotic process (GO:0042981), negative regulation of apoptotic process (GO:0043066), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), regulation of innate immune response (GO:0045088), regulation of inflammatory response (GO:0050727), regulation of cell cycle (GO:0051726), regulation of necroptotic process (GO:0060544), negative regulation of necroptotic process (GO:0060546), regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway (GO:0070424), negative regulation of programmed cell death (GO:0043069)

GO Molecular Function (8): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), transferase activity (GO:0016740), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), protein-containing complex binding (GO:0044877), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
TNF signaling	3
Immune System	2
Toll-like Receptor Cascades	2
Innate Immune System	2
Nucleotide-binding domain, leucine rich repeat containing receptor (NLR) signaling pathways	1
Toll Like Receptor 3 (TLR3) Cascade	1
Regulated Necrosis	1
Cytokine Signaling in Immune system	1
RIPK1-mediated regulated necrosis	1
TNFR2 non-canonical NF-kB pathway	1
Deubiquitination	1
TRIF (TICAM1)-mediated TLR4 signaling	1
Toll Like Receptor 4 (TLR4) Cascade	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
programmed cell death	2
intracellular signaling cassette	2
regulation of cytoplasmic pattern recognition receptor signaling pathway	2
apoptotic process	2
regulation of programmed cell death	2
regulation of defense response	2
regulation of response to external stimulus	2
necroptotic process	2
binding	2
apoptotic signaling pathway	1
execution phase of apoptosis	1
signal transduction	1
developmental process involved in reproduction	1
male gamete generation	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
cytokine-mediated signaling pathway	1
cellular response to tumor necrosis factor	1
toll-like receptor signaling pathway	1
regulation of pattern recognition receptor signaling pathway	1
RIG-I signaling pathway	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
regulation of response to biotic stimulus	1
innate immune response	1
regulation of immune response	1
inflammatory response	1
cell cycle	1
regulation of cellular process	1
regulation of programmed necrotic cell death	1
regulation of necroptotic process	1
negative regulation of programmed necrotic cell death	1
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	1
negative regulation of cellular process	1
ubiquitin-like protein transferase activity	1

Protein interactions and networks

STRING

3200 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BIRC3	TRAF1	Q13077	997
BIRC3	TRAF3	Q13114	995
BIRC3	RIPK1	Q13546	993
BIRC3	TRADD	Q15628	993
BIRC3	TRAF2	Q12933	990
BIRC3	TRAF5	O00463	977
BIRC3	BIRC2	Q13490	952
BIRC3	DIABLO	Q9NR28	938
BIRC3	TRAF6	Q9Y4K3	937
BIRC3	TNFRSF1A	P19438	924
BIRC3	CASP3	P42574	922
BIRC3	XIAP	P98170	894
BIRC3	CYLD	Q9NQC7	858
BIRC3	TNF	P01375	849
BIRC3	UBE2N	P61088	839

IntAct

53 interactions, top by confidence:

A	B	Type	Score
MALT1	BCL10	psi-mi:“MI:0914”(association)	0.950
BIRC3	TRAF2	psi-mi:“MI:0915”(physical association)	0.860
BIRC3	TRAF2	psi-mi:“MI:2364”(proximity)	0.860
TRAF2	BIRC3	psi-mi:“MI:0915”(physical association)	0.860
BIRC3	TRAF2	psi-mi:“MI:0914”(association)	0.860
BCL10	TRAF2	psi-mi:“MI:0914”(association)	0.850
TNF	TRAF2	psi-mi:“MI:0914”(association)	0.840
TRAF2	HTRA2	psi-mi:“MI:0914”(association)	0.750
BIRC3	DIABLO	psi-mi:“MI:0915”(physical association)	0.670
BIRC3	TRAF1	psi-mi:“MI:2364”(proximity)	0.610
RIPK2	BIRC3	psi-mi:“MI:0915”(physical association)	0.600
BIRC3	RIPK1	psi-mi:“MI:0915”(physical association)	0.600
RIPK3	BIRC3	psi-mi:“MI:0915”(physical association)	0.600
RIPK4	BIRC3	psi-mi:“MI:0915”(physical association)	0.600
RIPK1	BIRC3	psi-mi:“MI:0915”(physical association)	0.600
BIRC3	RIPK2	psi-mi:“MI:0220”(ubiquitination reaction)	0.600
BIRC3	RIPK2	psi-mi:“MI:0915”(physical association)	0.600
BIRC3	RIPK3	psi-mi:“MI:0915”(physical association)	0.600
BIRC3	RIPK4	psi-mi:“MI:0915”(physical association)	0.600
UBE2N	BIRC3	psi-mi:“MI:0915”(physical association)	0.590
BIRC3	UBE2D2	psi-mi:“MI:0407”(direct interaction)	0.520
BIRC3	CASP9	psi-mi:“MI:0915”(physical association)	0.520
BIRC3	CASP9	psi-mi:“MI:2364”(proximity)	0.520
	BIRC3	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (1513): HAX1 (Affinity Capture-Western), BIRC3 (Affinity Capture-Western), BIRC3 (Reconstituted Complex), HAX1 (Reconstituted Complex), BIRC3 (Biochemical Activity), UBE2D2 (Reconstituted Complex), BIRC3 (Reconstituted Complex), BIRC3 (Affinity Capture-Western), RIPK1 (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2V1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), BIRC3 (Biochemical Activity), UBE2D2 (Reconstituted Complex), TRAF2 (Biochemical Activity)

ESM2 similar proteins: A1E2V0, A5D8Q0, A9JTP3, A9ULZ2, B1B1A0, O08863, O62640, P33279, P36406, P36407, P42573, P51784, P98170, Q13049, Q13075, Q13489, Q13490, Q1L8G6, Q24307, Q4R8E0, Q5BKL8, Q60989, Q62210, Q63185, Q6P5D3, Q6ZPS6, Q6ZUJ8, Q7Z2W4, Q80Z32, Q8C7M3, Q8CH72, Q8JHV9, Q8K337, Q8N1W1, Q8R151, Q90660, Q95M71, Q95M72, Q96P09, Q9BQI3

Diamond homologs: A1E2V0, A1L020, A1L3F4, A5D8Q0, A9JTP3, A9ULZ2, D3ZDI6, E3SCZ8, O08863, O10296, O10324, O14064, O15392, O62640, O70201, O88738, P40629, P41435, P41436, P41437, P41454, P47732, P98170, Q05AK5, Q0WPJ7, Q13489, Q13490, Q28ER3, Q28H51, Q50L39, Q557E7, Q5BKL8, Q5R881, Q5RAH9, Q60989, Q62210, Q69Z36, Q6I6F4, Q6J1J1, Q6NTT6

SIGNOR signaling

31 interactions.

A	Effect	B	Mechanism
BIRC3	“down-regulates activity”	BIRC3	ubiquitination
DIABLO	“down-regulates quantity”	BIRC3	binding
BIRC3	“up-regulates activity”	RIPK1	ubiquitination
XAF1	down-regulates	BIRC3	binding
TRAF2	up-regulates	BIRC3	binding
BIRC3	down-regulates	MAP3K14	ubiquitination
BIRC3	“down-regulates quantity by destabilization”	TRAF2	ubiquitination
AT-406	down-regulates	BIRC3	“chemical inhibition”
BIRC3	“up-regulates activity”	BIRC2	binding
PELI1	“up-regulates quantity by stabilization”	BIRC3	ubiquitination
ZNF804A	“down-regulates quantity by repression”	BIRC3	“transcriptional regulation”
Ub:E2	“up-regulates activity”	BIRC3	ubiquitination
BIRC3	“down-regulates quantity by destabilization”	DIABLO	ubiquitination
BIRC3	“down-regulates quantity by destabilization”	RIPK1	polyubiquitination
BIRC3	“up-regulates activity”	RIPK4	polyubiquitination
BIRC3	“up-regulates activity”	RIPK1	polyubiquitination
BIRC3	“up-regulates activity”	RIPK3	polyubiquitination
BIRC3	“up-regulates activity”	RIPK2	polyubiquitination
BIRC3	down-regulates	CASP9	binding
NFKB1	“up-regulates quantity by expression”	BIRC3	“transcriptional regulation”
NfKb-p65/p50	“up-regulates quantity by expression”	BIRC3	“transcriptional regulation”
DIABLO	“down-regulates activity”	BIRC3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 29 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
TICAM1, RIP1-mediated IKK complex recruitment	6	133.6×	3e-10
IKK complex recruitment mediated by RIP1	6	110.3×	7e-10
TNFR1-induced NF-kappa-B signaling pathway	6	74.6×	6e-09
Regulation of TNFR1 signaling	8	66.3×	4e-11
FCERI mediated NF-kB activation	7	40.6×	1e-08
Downstream TCR signaling	8	38.0×	1e-09
CLEC7A (Dectin-1) signaling	7	37.0×	2e-08
Antigen processing: Ubiquitination & Proteasome degradation	6	8.3×	7e-04

GO biological processes:

GO term	Partners	Fold	FDR
canonical NF-kappaB signal transduction	7	88.4×	3e-10
positive regulation of extrinsic apoptotic signaling pathway	5	78.5×	4e-07
tumor necrosis factor-mediated signaling pathway	6	68.4×	3e-08
obsolete positive regulation of NF-kappaB transcription factor activity	9	63.8×	4e-12
positive regulation of protein ubiquitination	5	36.8×	1e-05
negative regulation of canonical NF-kappaB signal transduction	5	29.6×	3e-05
T cell receptor signaling pathway	5	26.2×	4e-05
positive regulation of canonical NF-kappaB signal transduction	10	25.1×	5e-10

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — CLLSLL, LUSC.

Clinical variants and AI predictions

ClinVar

80 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	7
Uncertain significance	53
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (8)

Variant ID	HGVS	Classification
148976	GRCh38/hg38 11q14.3-22.3(chr11:91086659-109595582)x1	Pathogenic
3906844	NM_001165.5(BIRC3):c.103A>G (p.Thr35Ala)	Likely pathogenic
3906846	NM_001165.5(BIRC3):c.934C>T (p.His312Tyr)	Likely pathogenic
3906847	NM_001165.5(BIRC3):c.1566T>A (p.Tyr522Ter)	Likely pathogenic
3906848	NM_001165.5(BIRC3):c.1588G>C (p.Asp530His)	Likely pathogenic
3906849	NM_001165.5(BIRC3):c.1671T>A (p.Cys557Ter)	Likely pathogenic
3906850	NM_001165.5(BIRC3):c.1763G>A (p.Cys588Tyr)	Likely pathogenic
3906851	NM_001165.5(BIRC3):c.1813T>C (p.Ter605Arg)	Likely pathogenic

SpliceAI

889 predictions. Top by Δscore:

Variant	Effect	Δscore
11:102317581:G:GT	donor_gain	1.0000
11:102325561:CCAAG:C	donor_loss	1.0000
11:102325562:CAAG:C	donor_loss	1.0000
11:102325563:AAGG:A	donor_loss	1.0000
11:102325564:AGGTA:A	donor_loss	1.0000
11:102325566:GT:G	donor_loss	1.0000
11:102325567:T:G	donor_loss	1.0000
11:102328043:A:AG	acceptor_gain	1.0000
11:102328044:C:G	acceptor_gain	1.0000
11:102328045:A:AG	acceptor_gain	1.0000
11:102328046:T:G	acceptor_gain	1.0000
11:102328049:TAGGT:T	acceptor_loss	1.0000
11:102328050:A:AG	acceptor_gain	1.0000
11:102328050:AG:A	acceptor_gain	1.0000
11:102328050:AGGT:A	acceptor_gain	1.0000
11:102328051:G:A	acceptor_loss	1.0000
11:102328051:G:GA	acceptor_gain	1.0000
11:102328051:GG:G	acceptor_gain	1.0000
11:102328051:GGT:G	acceptor_gain	1.0000
11:102328051:GGTG:G	acceptor_gain	1.0000
11:102328051:GGTGT:G	acceptor_gain	1.0000
11:102328129:AGG:A	donor_loss	1.0000
11:102328131:G:C	donor_loss	1.0000
11:102328131:G:GG	donor_gain	1.0000
11:102328892:T:TA	acceptor_gain	1.0000
11:102328892:TGCA:T	acceptor_loss	1.0000
11:102328895:A:AG	acceptor_gain	1.0000
11:102328895:AG:A	acceptor_loss	1.0000
11:102328895:AGCT:A	acceptor_gain	1.0000
11:102328896:G:GT	acceptor_gain	1.0000

AlphaMissense

3983 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:102336956:T:C	C557R	0.999
11:102337049:T:C	C588R	0.999
11:102325351:T:C	F281S	0.998
11:102325486:T:C	C292R	0.998
11:102325516:T:A	W302R	0.998
11:102325516:T:C	W302R	0.998
11:102325518:G:C	W302C	0.998
11:102325518:G:T	W302C	0.998
11:102336956:T:A	C557S	0.998
11:102336957:G:A	C557Y	0.998
11:102336957:G:C	C557S	0.998
11:102336958:T:G	C557W	0.998
11:102336965:T:C	C560R	0.998
11:102337019:T:C	C578R	0.998
11:102324735:T:A	W76R	0.997
11:102324735:T:C	W76R	0.997
11:102325348:G:A	G280D	0.997
11:102325550:C:A	A313D	0.997
11:102328053:T:C	C319R	0.997
11:102336965:T:A	C560S	0.997
11:102336966:G:C	C560S	0.997
11:102337028:T:C	C581R	0.997
11:102324737:G:C	W76C	0.996
11:102324737:G:T	W76C	0.996
11:102325154:G:C	W215C	0.996
11:102325154:G:T	W215C	0.996
11:102325486:T:A	C292S	0.996
11:102325487:G:C	C292S	0.996
11:102325558:T:C	F316L	0.996
11:102325560:T:A	F316L	0.996

dbSNP variants (sampled 300 via entrez): RS1000216597 (11:102339222 A>G,T), RS1000279607 (11:102326827 G>A), RS1000310889 (11:102331821 A>C), RS1000399584 (11:102332744 C>G), RS1000616550 (11:102338992 T>A,C), RS1000881719 (11:102328291 G>A), RS1000941147 (11:102320147 G>A), RS1000972403 (11:102320316 A>G), RS1001034469 (11:102321713 C>T), RS1001337955 (11:102333462 A>G), RS1001355046 (11:102328635 T>C), RS1001442554 (11:102334677 T>G), RS1001482129 (11:102326843 G>A), RS1001553408 (11:102316971 C>G,T), RS1001815025 (11:102334304 G>A)

Disease associations

OMIM: gene MIM:601721 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

17 total (17 of 17 shown, HPO-id order):

HPO	Term
HP:0000505	Visual impairment
HP:0000614	Abnormal nasolacrimal system morphology
HP:0000820	Abnormality of the thyroid gland
HP:0000975	Hyperhidrosis
HP:0001824	Weight loss
HP:0001903	Anemia
HP:0001945	Fever
HP:0002017	Nausea and vomiting
HP:0002019	Constipation
HP:0002027	Abdominal pain
HP:0002113	Pulmonary infiltrates
HP:0002205	Recurrent respiratory infections
HP:0002716	Lymphadenopathy
HP:0012123	Posterior uveitis
HP:0012191	B-cell lymphoma
HP:0012378	Fatigue
HP:0100721	Mediastinal lymphadenopathy

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST000895_4	Whole-brain volume (Alzheimer’s disease interaction)	1.000000e-06
GCST001942_2	Prostate cancer	2.000000e-11

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005089	whole-brain volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL3038465 (PROTEIN FAMILY), CHEMBL3885522 (CHIMERIC PROTEIN), CHEMBL4296121 (PROTEIN-PROTEIN INTERACTION), CHEMBL5335 (SINGLE PROTEIN), CHEMBL5465215 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465242 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066573 (PROTEIN FAMILY), CHEMBL6066574 (PROTEIN FAMILY), CHEMBL6193801 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193813 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 3,251 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL2158051	XEVINAPANT	3	680
CHEMBL2431768	LCL-161	2	1,365
CHEMBL3039522	BIRINAPANT	2	925
CHEMBL2063869	GDC-0152	1	281

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Inhibitors of apoptosis (IAP) protein family

Most potent curated ligand interactions (5 total), top 5:

Ligand	Action	Affinity	Parameter
SM-122	Inhibition	8.74	pKi
SM-337	Antagonist	8.38	pKi
xevinapant	Antagonist	8.29	pKi
AZD5582	Antagonist	7.68	pIC50
GDC-0152	Antagonist	7.37	pKi

Binding affinities (BindingDB)

347 measured of 404 human assays (463 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl (8R,12S,15S,18S,29R,33S,36S,39S)-39-cyano-11,32-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,36-bis(naphthalen-2-ylmethyl)-13,16,34,37-tetraoxo-2,23-dioxa-5,6,7,11,14,17,26,27,28,32,35,38-dodecazaheptacyclo[39.2.2.219,22.14,7.125,28.08,12.029,33]nonatetraconta-1(44),4(49),5,19,21,25(46),26,41(45),42,47-decaene-18-carboxylate	IC50	0.3 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18R,30R,34S,37S,40S)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-40-(5-oxo-1,2,4-oxadiazolidin-3-yl)-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylic acid	IC50	0.4 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(4R,8S,11S,14R,24R,28S,31S,34R)-7,27-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-11,31-bis(naphthalen-2-ylmethyl)-9,12,29,32-tetraoxo-3,23-dioxa-7,10,13,18,19,20,27,30,33,38,39,40-dodecazapentacyclo[36.2.1.118,21.04,8.024,28]dotetraconta-1(41),19,21(42),39-tetraene-14,34-dicarboxylic acid	IC50	0.8 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18R,30R,34S,37S,40S)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-40-(5-sulfanylidene-1,2,4-oxadiazolidin-3-yl)-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylic acid	IC50	0.8 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(2R,5S,8S)-8-[(2S)-2-(methylamino)propanamido]-7-oxo-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-6-azatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),11,13-triene-5-carboxamide	KI	1.1 nM
(8R,12S,15S,18S,30R,34S,37S,40S)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18,40-dicarboxylic acid	IC50	1.1 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18S,30R,34S,39R,42S)-42-[(3,5-difluoro-4-hydroxyphenyl)methylcarbamoyl]-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,39-bis(naphthalen-2-ylmethyl)-13,16,35,37,40-pentaoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,41-dodecazaheptacyclo[42.2.2.220,23.14,7.126,29.08,12.030,34]dopentaconta-1(47),4(52),5,20,22,26(49),27,44(48),45,50-decaene-18-carboxylic acid	IC50	1.2 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
BMC175834 Compound 1b	KI	1.3 nM
(8R,12S,15S,18S,30R,34S,37S,40S)-40-(cyclopropylsulfonylcarbamoyl)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylic acid	IC50	1.3 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18S,30R,34S,39R,42S)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,39-bis(naphthalen-2-ylmethyl)-13,16,35,37,40-pentaoxo-18-(2-oxo-3H-1,3,4-oxadiazol-5-yl)-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,41-dodecazaheptacyclo[42.2.2.220,23.14,7.126,29.08,12.030,34]dopentaconta-1(47),4(52),5,20,22,26(49),27,44(48),45,50-decaene-42-carboxylic acid	IC50	1.3 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18S,30R,34S,39R,42S)-42-[[(3R,5R)-6-carboxy-3,5-dihydroxyhexyl]carbamoyl]-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,39-bis(naphthalen-2-ylmethyl)-13,16,35,37,40-pentaoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,41-dodecazaheptacyclo[42.2.2.220,23.14,7.126,29.08,12.030,34]dopentaconta-1(47),4(52),5,20,22,26(49),27,44(48),45,50-decaene-18-carboxylic acid	IC50	1.4 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(4R,8S,11S,16S,23R,27S,30S,35S)-7,26-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-11,30-bis(naphthalen-2-ylmethyl)-9,12,28,31-tetraoxo-3,22-dioxa-7,10,13,17,18,19,26,29,32,36,37,38-dodecazapentacyclo[34.2.1.117,20.04,8.023,27]tetraconta-1(39),18,20(40),37-tetraene-16,35-dicarboxylic acid	IC50	1.6 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
methyl (8R,12S,15S,18S,29R,33S,36S,39S)-39-cyano-11,32-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-[methyl-[(2-methylpropan-2-yl)oxycarbonyl]amino]propanoyl]amino]butanoyl]-15,36-bis(naphthalen-2-ylmethyl)-13,16,34,37-tetraoxo-2,23-dioxa-5,6,7,11,14,17,26,27,28,32,35,38-dodecazaheptacyclo[39.2.2.219,22.14,7.125,28.08,12.029,33]nonatetraconta-1(44),4(49),5,19,21,25(46),26,41(45),42,47-decaene-18-carboxylate	IC50	2.2 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
methyl (8R,12S,15S,18S,30R,34S,37S,40S)-40-(cyclopropylsulfonylcarbamoyl)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylate	IC50	2.4 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
methyl (8R,12S,15S,18S,30R,34S,39R,42S)-42-[(3,5-difluoro-4-hydroxyphenyl)methylcarbamoyl]-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,39-bis(naphthalen-2-ylmethyl)-13,16,35,37,40-pentaoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,41-dodecazaheptacyclo[42.2.2.220,23.14,7.126,29.08,12.030,34]dopentaconta-1(47),4(52),5,20,22,26(49),27,44(48),45,50-decaene-18-carboxylate	IC50	2.7 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18S,30R,34S,37S,40S)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-40-(5-oxo-1,2,4-oxadiazolidin-3-yl)-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylic acid	IC50	2.9 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(2R,5S,8S)-N-(diphenylmethyl)-8-[(2S)-2-(methylamino)propanamido]-7-oxo-6-azatricyclo[8.4.0.0^{2,6}]tetradeca-1(10),11,13-triene-5-carboxamide	KI	3 nM
4-N-[(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-7-yl]-1-N-[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]benzene-1,4-dicarboxamide	IC50	3 nM	US-9783573: IAP antagonists
N’-[(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-7-yl]-N-[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]oxamide	IC50	3 nM	US-9783573: IAP antagonists
4-N-[(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-6-yl]-1-N-[(5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]benzene-1,4-dicarboxamide	IC50	4 nM	US-9783573: IAP antagonists
(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-7-[[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]carbamoylamino]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-3,4-dihydro-1H-isoquinoline-3-carboxamide	IC50	4 nM	US-9783573: IAP antagonists
(S)-2-((S)-3,3-Dimethyl-2-((S)-2-(methylamino) propanamido)butanoyl)-N7-(4-(((3S,5S)-1-((S)-3,3- dimethyl-2-((S)-2-(methylamino)propanamido) butanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1- yl)carbamoyl)pyrrolidin-3-yl)carbamoyl)oxazol-2-yl)- N3-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4- tetrahydroisoquinoline-3,7-dicarboxamide	IC50	4 nM	US-9783573: IAP antagonists
(S)-2-((S)-3,3-Dimethyl-2-((S)-2-(methylamino) propanamido)butanoyl)-N7-((5-(((3S,5S)-1-((S)-3,3- dimethyl-2-((S)-2-(methylamino)propanamido) butanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1- yl)carbamoyl)pyrrolidin-3-yl)carbamoyl)pyridin-2- yl)methyl)-N3-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)- 1,2,3,4-tetrahydroisoquinoline-3,7-dicarboxamide	IC50	4 nM	US-9783573: IAP antagonists
1-N-[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]-4-N-[(3S)-2-[(2R)-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-methylsulfanylbutanoyl]-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-7-yl]benzene-1,4-dicarboxamide	IC50	4 nM	US-9783573: IAP antagonists
(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-7-N-[5-[[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]carbamoyl]-1,3-oxazol-2-yl]-3-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4-dihydro-1H-isoquinoline-3,7-dicarboxamide	IC50	4 nM	US-9783573: IAP antagonists
(S)-2-((S)-3,3-Dimethyl-2-((S)-2-(methylamino) propanamido)butanoyl)-N7-(6-(((3S,5S)-1-((S)-3,3- dimethyl-2-((S)-2-(methylamino)propanamido) butanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1- yl)carbamoyl)pyrrolidin-3-yl)carbamoyl)-5- methylpyrrolo[2,1-f][1,2,4]triazin-4-yl)-N3-((R)- 1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4- tetrahydroisoquinoline-3,7-dicarboxamide	IC50	5 nM	US-9783573: IAP antagonists
N1-((3S,5S)-1-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N4- ((S)-2-((R)-3-((2-((2-hydroxyethyl)amino)-2- oxoethyl)thio)-3-methyl-2-((S)-2- (methylamino)propanamido)butanoyl)-3-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4- tetrahydroisoquinolin-7-yl)terephthalamide	IC50	5 nM	US-9783573: IAP antagonists
(4R,8S,11S,14R,23R,27S,30S,33R)-7,26-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-11,30-bis(naphthalen-2-ylmethyl)-9,12,28,31-tetraoxo-3,22-dioxa-7,10,13,17,18,19,26,29,32,36,37,38-dodecazapentacyclo[34.2.1.117,20.04,8.023,27]tetraconta-1(39),18,20(40),37-tetraene-14,33-dicarboxylic acid	IC50	5.2 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(8R,12S,15S,18S,30R,34S,37R,40S)-40-(cyclopropylsulfonylcarbamoyl)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylic acid	IC50	5.7 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
(S)-2-((S)-3,3-Dimethyl-2-((S)-2-(methylamino) propanamido)butanoyl)-N7-(5-(((3S,5S)-1-((S)-3,3- dimethyl-2-((S)-2-(methylamino)propanamido) butanoyl)-5-(((R)-1,2,3,4-tetrahydronaphthalen-1- yl)carbamoyl)pyrrolidin-3-yl)carbamoyl)thiazol-2-yl)- N3-((R)-1,2,3,4-tetrahydronaphthalen-1-yl)-1,2,3,4- tetrahydroisoquinoline-3,7-dicarboxamide	IC50	6 nM	US-9783573: IAP antagonists
1-N-[(5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]-4-N-[2-[(2R)-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-methylsulfanylbutanoyl]-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-7-yl]benzene-1,4-dicarboxamide	IC50	6 nM	US-9783573: IAP antagonists
N1-((3S,5S)-1-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N4-((S)- 2-((R)-3-((2-hydroxyethyl)thio)-3-methyl-2-((S)-2- (methylamino)propanamido)butanoyl)-3-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4- tetrahydroisoquinolin-7-yl)terephthalamide	IC50	6 nM	US-9783573: IAP antagonists
(8R,12R,13R,16S,28R,32S,35R,38S)-11,31-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-38-methoxycarbonyl-13,35-bis(naphthalen-2-ylmethyl)-14,33,36-trioxo-2,22-dioxa-5,6,7,11,15,25,26,27,31,37-decazaheptacyclo[38.2.2.218,21.14,7.124,27.08,12.028,32]octatetraconta-1(43),4(48),5,18,20,24(45),25,40(44),41,46-decaene-16-carboxylic acid	IC50	6.5 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
N1-((35,5S)-1-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N4- ((S)-2-((R)-3-((2-((2-hydroxyethyl)(methyl)amino)-2- oxoethyl)thio)-3-methyl-2-((S)-2- (methylamino)propanamido)butanoyl)-3-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4- tetrahydroisoquinolin-7-yl)terephthalamide	IC50	7 nM	US-9783573: IAP antagonists
(4R,8S,11S,17S,24R,28S,31S,37S)-7,27-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-17-N,37-N-bis(methylsulfonyl)-11,31-bis(naphthalen-2-ylmethyl)-9,12,29,32-tetraoxo-3,23-dioxa-7,10,13,18,19,20,27,30,33,38,39,40-dodecazapentacyclo[36.2.1.118,21.04,8.024,28]dotetraconta-1(41),19,21(42),39-tetraene-17,37-dicarboxamide	IC50	8 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
CS-1	KI	10 nM
N1-((3S,5S)-1-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N4- ((S)-2-((R)-3-((2-(dimethylamino)-2-oxoethyl)thio)-3- methyl-2-((S)-2-(methylamino)propanamido)butanoyl)-3- (((R)-1,2,3,4-tetrahydronaphthalen-1-yl)carbamoyl)- 1,2,3,4-tetrahydroisoquinolin-7-yl)terephthalamide	IC50	10 nM	US-9783573: IAP antagonists
N1-((S)-2-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-3- (((R)-2-methoxy-1-phenylethyl)carbamoyl)- 1,2,3,4-tetrahydroisoquinolin-7-yl)-N4- ((3S,5S)-1-((S)-3,3-dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5- (((R)-1,2,3,4-tetrahydronaphthalen-1- yl)carbamoyl)pyrrolidin-3-yl)terephthalamide	IC50	11 nM	US-9783573: IAP antagonists
(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-7-N-[5-[[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]carbamoyl]-1,3-benzothiazol-2-yl]-3-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-3,4-dihydro-1H-isoquinoline-3,7-dicarboxamide	IC50	11 nM	US-9783573: IAP antagonists
N1-((S)-2-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-3- (((R)-1-(2-fluorophenyl)ethyl)carbamoyl)- 1,2,3,4-tetrahydroisoquinolin-7-yl)-N4- ((3S,5S)-1-((S)-3,3-dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5- (((R)-1,2,3,4-tetrahydronaphthalen-1- yl)carbamoyl)pyrrolidin-3-yl)terephthalamide	IC50	12 nM	US-9783573: IAP antagonists
2-[(3R)-4-[(3S)-7-[[4-[[(3S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]carbamoyl]benzoyl]amino]-3-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-2-yl]-2-methyl-3-[[(2S)-2-(methylamino)propanoyl]amino]-4-oxobutan-2-yl]sulfanylethyl formate	IC50	12 nM	US-9783573: IAP antagonists
(2R,6S,9S)-N-(diphenylmethyl)-9-[(2S)-2-(methylamino)propanamido]-8-oxo-7-azatricyclo[9.4.0.0^{2,7}]pentadeca-1(15),11,13-triene-6-carboxamide	KI	13 nM
CS-3	KI	16 nM
N1-((3S,5S)-1-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido)butanoyl)-5-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)pyrrolidin-3-yl)-N4- ((S)-2-((R)-3-methyl-2-((S)-2- (methylamino)propanamido)-3-((2-morpholino-2- oxoethyl)thio)butanoyl)-3-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl)-1,2,3,4- tetrahydroisoquinolin-7-yl)terephthalamide	IC50	16 nM	US-9783573: IAP antagonists
(3S)-2-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-7-[[4-[[(3S,5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-3-yl]carbamoyl]phenyl]methoxy]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4-dihydro-1H-isoquinoline-3-carboxamide	IC50	16 nM	US-9783573: IAP antagonists
(8R,12S,15S,18S,30R,34S,37S,40S)-11,33-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-15,37-bis(naphthalen-2-ylmethyl)-13,16,35,38-tetraoxo-40-(pyridin-2-ylsulfonylcarbamoyl)-2,24-dioxa-5,6,7,11,14,17,27,28,29,33,36,39-dodecazaheptacyclo[40.2.2.220,23.14,7.126,29.08,12.030,34]pentaconta-1(45),4(50),5,20,22,26(47),27,42(46),43,48-decaene-18-carboxylic acid	IC50	16.9 nM	US-9605022: Macrocyclic compounds for inhibition of inhibitors of apoptosis
1-N-[(5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]-4-N-[2-[(2R)-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-(2-oxo-2-piperidin-1-ylethyl)sulfanylbutanoyl]-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]-3,4-dihydro-1H-isoquinolin-7-yl]benzene-1,4-dicarboxamide	IC50	18 nM	US-9783573: IAP antagonists
N4-((S)-2-((S)-3,3-Dimethyl-2-((S)-2- (methylamino)propanamido) butanoyl)-3-(((R)-1,2,3,4- tetrahydronaphthalen-1- yl)carbamoyl)-1,2,3,4- tetrahydroisoquinolin-7-yl)-N1- ((3S,5S)-1-((S)-3,3-dimethyl-2-((S)-2- (methylamino)propanamido) butanoyl)-5-(((R)-1,2,3,4- tetrahydronaphthalen-1-yl)carbamoyl) pyrrolidin-3-yl)-1H-indole-1,4- dicarboxamide	IC50	21 nM	US-9783573: IAP antagonists
(S)—N—((S)-1-((6-Bromo-2-methoxynaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl)-2-(2-hydroxyethylamino)butanamide	IC50	22 nM	US-9611224: Antiproliferative benzo [B] azepin-2-ones
5-N-[(3S)-2-[3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-3-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)-3,4-dihydro-1H-isoquinolin-7-yl]-1-N-[(5S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-5-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)pyrrolidin-3-yl]indole-1,5-dicarboxamide	IC50	22 nM	US-9783573: IAP antagonists

ChEMBL bioactivities

400 potent at pChembl≥5 of 402 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.51	IC50	0.031	nM	CHEMBL3806155
10.27	IC50	0.054	nM	CHEMBL3805576
10.08	IC50	0.084	nM	CHEMBL3805390
9.93	IC50	0.117	nM	CHEMBL3806235
9.88	IC50	0.132	nM	CHEMBL3806279
9.77	IC50	0.17	nM	CHEMBL3806299
9.60	Ki	0.25	nM	CHEMBL475670
9.00	Ki	1	nM	CHEMBL481213
8.92	Ki	1.2	nM	CHEMBL1774157
8.89	Ki	1.3	nM	CHEMBL2158601
8.89	IC50	1.3	nM	CHEMBL2316217
8.77	Ki	1.7	nM	CHEMBL2158053
8.77	Ki	1.7	nM	CHEMBL2158600
8.77	IC50	1.7	nM	CHEMBL3217229
8.73	Ki	1.84	nM	CHEMBL481422
8.72	Kd	1.9	nM	CHEMBL2158054
8.72	IC50	1.9	nM	CHEMBL5799178
8.72	IC50	1.9	nM	CHEMBL5916145
8.70	Ki	2	nM	CHEMBL1774154
8.70	Ki	2	nM	CHEMBL2158599
8.70	IC50	2	nM	CHEMBL5806178
8.70	Ki	2	nM	CHEMBL1774156
8.70	Ki	2	nM	CHEMBL1774158
8.70	Ki	2	nM	CHEMBL1774031
8.70	Ki	2	nM	CHEMBL1774160
8.68	IC50	2.1	nM	CHEMBL3142652
8.68	Ki	2.1	nM	CHEMBL2348619
8.68	Ki	2.09	nM	CHEMBL472832
8.60	IC50	2.5	nM	CHEMBL3217017
8.60	Ki	2.5	nM	CHEMBL1774161
8.60	Ki	2.5	nM	CHEMBL1774163
8.59	IC50	2.6	nM	CHEMBL3216800
8.57	IC50	2.7	nM	CHEMBL3215905
8.52	Ki	3	nM	CHEMBL456400
8.52	IC50	3	nM	CHEMBL3609325
8.52	IC50	3	nM	CHEMBL3410872
8.52	IC50	3	nM	CHEMBL3339214
8.52	Ki	3	nM	CHEMBL1774159
8.52	Ki	3	nM	CHEMBL1774162
8.49	IC50	3.2	nM	CHEMBL3217228
8.49	IC50	3.2	nM	CHEMBL5984721
8.48	Ki	3.3	nM	CHEMBL2158602
8.47	IC50	3.4	nM	CHEMBL3216798
8.40	Ki	4	nM	CHEMBL2158606
8.40	IC50	4	nM	CHEMBL3215907
8.40	IC50	4	nM	CHEMBL5881153
8.40	IC50	4	nM	CHEMBL5977733
8.40	IC50	4	nM	CHEMBL5768777
8.40	IC50	4	nM	CHEMBL3339219
8.40	IC50	4	nM	CHEMBL5783915

PubChem BioAssay actives

271 with measured affinity, of 447 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
1-[2-chloro-7-[(1S)-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]-3-[6-(triazol-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	1299813: Inhibition of cIAP2-MALT1 (unknown origin) expressed in HEK293 cells assessed as inhibition of NFkappaB signaling after 24 hrs by luciferase reporter gene assay	ic50	<0.0001	uM
1-[2-chloro-7-(oxolan-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[6-(triazol-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	1299813: Inhibition of cIAP2-MALT1 (unknown origin) expressed in HEK293 cells assessed as inhibition of NFkappaB signaling after 24 hrs by luciferase reporter gene assay	ic50	0.0001	uM
1-[7-[(1S)-1-methoxyethyl]-2-methylpyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-(trifluoromethyl)-3-pyridinyl]urea	1299813: Inhibition of cIAP2-MALT1 (unknown origin) expressed in HEK293 cells assessed as inhibition of NFkappaB signaling after 24 hrs by luciferase reporter gene assay	ic50	0.0001	uM
1-(2-chloro-7-propan-2-ylpyrazolo[1,5-a]pyrimidin-6-yl)-3-[6-(1,1-dioxo-1,2-thiazolidin-2-yl)-5-(trifluoromethyl)-3-pyridinyl]urea	1299813: Inhibition of cIAP2-MALT1 (unknown origin) expressed in HEK293 cells assessed as inhibition of NFkappaB signaling after 24 hrs by luciferase reporter gene assay	ic50	0.0001	uM
1-[2-chloro-7-(1-cyclopropyl-2-methoxyethyl)pyrazolo[1,5-a]pyrimidin-6-yl]-3-[5-chloro-6-(triazol-2-yl)-3-pyridinyl]urea	1299813: Inhibition of cIAP2-MALT1 (unknown origin) expressed in HEK293 cells assessed as inhibition of NFkappaB signaling after 24 hrs by luciferase reporter gene assay	ic50	0.0001	uM
1-[4-[4-(aminomethyl)pyrazol-1-yl]-3-chlorophenyl]-3-(2-chloro-7-propan-2-ylpyrazolo[1,5-a]pyrimidin-6-yl)urea	1299813: Inhibition of cIAP2-MALT1 (unknown origin) expressed in HEK293 cells assessed as inhibition of NFkappaB signaling after 24 hrs by luciferase reporter gene assay	ic50	0.0002	uM
(1S,3S,6S,10aS)-1-benzyl-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	368237: Displacement of fluorescent SM5F peptide from His-tagged human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0003	uM
(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	368237: Displacement of fluorescent SM5F peptide from His-tagged human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0010	uM
(3S,6S,10aS)-N-[(S)-[1-[3-[4-[3-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]propyl]phenyl]propyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0012	uM
(3S,7R,8aR)-2-[(2S)-2-(4,4-difluorocyclohexyl)-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-7-ethoxy-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0013	uM
(5S,8S,10aR)-3-[6-[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-3-yl]-6-oxohexanoyl]-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	694874: Binding affinity to BIR3 domain of cIAP2 by fluorescence polarization assay	ki	0.0013	uM
(5S,8S,10aR)-N-[(S)-[1-[10-[6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]hexanoylamino]decyl]triazol-4-yl]-phenylmethyl]-5-[[(2S)-2-(methylamino)propanoyl]amino]-3-(3-methylbutanoyl)-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	695457: Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	ki	0.0017	uM
(5S,8S,10aR)-3-[4-[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-3-yl]-4-oxobutanoyl]-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	694874: Binding affinity to BIR3 domain of cIAP2 by fluorescence polarization assay	ki	0.0017	uM
(3S,8aR)-2-[(2S)-2-(4,4-difluorocyclohexyl)-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-7,7-difluoro-1,3,4,6,8,8a-hexahydropyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0017	uM
(3S,6S,10aS)-N-benzhydryl-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	368237: Displacement of fluorescent SM5F peptide from His-tagged human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0018	uM
5-[10-[4-[(S)-[[(5S,8S,10aR)-5-[[(2S)-2-(methylamino)propanoyl]amino]-3-(3-methylbutanoyl)-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carbonyl]amino]-phenylmethyl]triazol-1-yl]decylcarbamoyl]-2-(3-hydroxy-6-oxoxanthen-9-yl)benzoic acid	695454: Binding affinity to human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) assessed as dissociation constant after 2 to 3 hrs by fluorescence polarization assay	kd	0.0019	uM
(3S,6S,10aS)-N-[(S)-[1-[4-[4-[4-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]butyl]phenyl]butyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0020	uM
(3S,6S,10aS)-N-[(S)-[1-[2-[4-[2-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]ethyl]phenyl]ethyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0020	uM
(3S,6S,10aS)-N-[(S)-[1-[6-[4-[6-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]hexyl]phenyl]hexyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0020	uM
(3S,6S,10aS)-N-[(S)-[1-[10-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]decyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0020	uM
(3S,6S,10aS)-N-[(S)-[1-[12-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]dodecyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0020	uM
(3S,6S,10aS)-N-[(S)-[1-[8-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]octyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	694874: Binding affinity to BIR3 domain of cIAP2 by fluorescence polarization assay	ki	0.0020	uM
(1S,3S,6S,8Z,10aS)-1-benzyl-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-2,3,6,7,10,10a-hexahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	368237: Displacement of fluorescent SM5F peptide from His-tagged human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0021	uM
(3S,8aR)-2-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0021	uM
(5S,8S,10aR)-3-N-[4-[4-[[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3-carbonyl]amino]phenoxy]phenyl]-8-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3,8-dicarboxamide	740368: Binding affinity to cIAP2 BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-2F	ki	0.0021	uM
(3S,6S,10aS)-N-[(S)-[1-[4-[1-[4-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]butyl]triazol-4-yl]butyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0025	uM
(3S,6S,10aS)-N-[(S)-[1-[5-[5-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]pentoxy]pentyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0025	uM
(3S,8aS)-2-[(2S)-2-(4,4-difluorocyclohexyl)-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0025	uM
(3S,8aR)-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-2-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]-2-phenylacetyl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0026	uM
(3S,8aR)-2-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0027	uM
(8S,11S,14S,17S,28S,31S,34S,37R)-37-(cyclopropylsulfonylamino)-10,30-bis[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-14,34-bis(naphthalen-2-ylmethyl)-12,15,32,35-tetraoxo-2,23-dioxa-5,6,7,10,13,16,30,33,36-nonazahexacyclo[37.2.2.219,22.14,7.18,11.128,31]octatetraconta-1(42),4(48),5,19,21,39(43),40,45-octaene-17-carboxylic acid	1242415: Inhibition of cIAP BIR2-3 domain (unknown origin)	ic50	0.0030	uM
(5S,8S,10aR)-3-acetyl-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	694874: Binding affinity to BIR3 domain of cIAP2 by fluorescence polarization assay	ki	0.0030	uM
(3S,6S,10aS)-N-[(S)-[1-[8-[4-[8-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]octyl]phenyl]octyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0030	uM
(3S,6S,10aS)-N-[(S)-[1-[4-[4-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]butylcarbamoylamino]butyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0030	uM
(3S,8aR)-2-[(2S)-2-(4,4-difluorocyclohexyl)-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0032	uM
(5S,8S,10aR)-3-[8-[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-3-yl]-8-oxooctanoyl]-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	694874: Binding affinity to BIR3 domain of cIAP2 by fluorescence polarization assay	ki	0.0033	uM
(3S,8aR)-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-2-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]-2-(oxan-4-yl)acetyl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0034	uM
(3S,6S,10aS)-N-[(S)-[1-[2-[4-[2-[4-[(S)-[[(3S,6S,10aS)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carbonyl]amino]-phenylmethyl]triazol-1-yl]ethoxy]butoxy]ethyl]triazol-4-yl]-phenylmethyl]-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	596706: Binding affinity to human cIAP2 BIR3 domain after 2 to 3 hrs by fluorescence polarization-based assay	ki	0.0040	uM
(5S,8S,10aR)-3-[5-[5-[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocin-3-yl]-5-oxopentoxy]pentanoyl]-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	694874: Binding affinity to BIR3 domain of cIAP2 by fluorescence polarization assay	ki	0.0040	uM
(3S,8aR)-2-[(2S)-2-cyclohexyl-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(1R)-4,4-difluoro-2,3-dihydro-1H-naphthalen-1-yl]-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0040	uM
(3S,6S,11bR)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,2,3,6,7,11b-hexahydropyrrolo[2,1-a][2]benzazepine-3-carboxamide	1798648: Fluorescence Polarization Assay from Article 10.1021/jm801146d: “Design, Synthesis, and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases.”	ki	0.0042	uM
(3S,6S,9R,10aR)-N-benzhydryl-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-9-[(2-phenylacetyl)amino]-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	511587: Displacement of fluorescent SM5F peptide from His-tagged human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0042	uM
(3S,6S,9aS)-N-benzhydryl-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxamide	1798648: Fluorescence Polarization Assay from Article 10.1021/jm801146d: “Design, Synthesis, and Evaluation of Tricyclic, Conformationally Constrained Small-Molecule Mimetics of Second Mitochondria-Derived Activator of Caspases.”	ki	0.0048	uM
(3S,6S,9aS)-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-N,N-diphenyl-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepine-3-carboxamide	348076: Displacement of fluorescently tagged SMF5 from human cloned cIAP2 BIR3 expressed in Escherichia coli BL21 (DE3) by competitive fluorescence polarization assay	ki	0.0048	uM
(3S,7R,8aR)-2-[(2S)-2-(4,4-difluorocyclohexyl)-2-[[(2S)-2-(methylamino)propanoyl]amino]acetyl]-N-[(4R)-3,4-dihydro-2H-chromen-4-yl]-7-hydroxy-3,4,6,7,8,8a-hexahydro-1H-pyrrolo[1,2-a]pyrazine-3-carboxamide;dihydrochloride	725259: Inhibition of human recombinant His-tagged cIAP1 protein BIR3 domain (250 to 350 amino acid residues) using biotinylated-Smac as substrate after overnight incubation by HTRF assay	ic50	0.0049	uM
1-[2-[(2R,5R)-2-[[(2R)-4-[5-[4-[3-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1H-pyrazol-3-yl)amino]quinazolin-7-yl]oxypropyl]piperazine-1-carbonyl]pyrimidin-2-yl]-2-methylpiperazin-1-yl]methyl]-5-methylpiperazin-1-yl]acetyl]-6-[(4-fluorophenyl)methyl]-3,3,4-trimethyl-2H-pyrrolo[3,2-b]pyridin-5-one	1773570: Binding affinity to human 6His-thr cIAP1 BIR3 (253 to 363) domain expressed in Escherichia coli measured after 105 mins in dark by time-resolved fluorescence laser-equipped multimode plate reader	ic50	0.0050	uM
(5S,8S,10aR)-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-3-(3-methylbutanoyl)-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	695457: Competitive inhibition of human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) after 2 to 3 hrs by fluorescence polarization assay	ki	0.0051	uM
(3S,6S,9R,10aR)-6-[[(2S)-2-(methylamino)propanoyl]amino]-5-oxo-9-[(2-phenylacetyl)amino]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-2,3,6,7,8,9,10,10a-octahydro-1H-pyrrolo[1,2-a]azocine-3-carboxamide	511587: Displacement of fluorescent SM5F peptide from His-tagged human cIAP2 BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ic50	0.0053	uM
(5S,8S,10aR)-3-N-[4-[[(5S,8S,10aR)-8-(benzhydrylcarbamoyl)-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3-carbonyl]amino]phenyl]-8-N-benzhydryl-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-3,8-dicarboxamide	740368: Binding affinity to cIAP2 BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-2F	ki	0.0054	uM
(2S)-N-[(1S)-1-cyclohexyl-2-[(2S)-2-[4-(3-methoxybenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide	1503860: Inhibition of recombinant human His-tagged cIAP2 (Gln238 to Ser349 residues) expressed in Escherichia coli by TR-FRET assay	ic50	0.0057	uM

CTD chemical–gene interactions

248 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, affects expression, decreases expression	10
Arsenic Trioxide	affects cotreatment, decreases expression, increases reaction, increases expression, affects expression	8
Estradiol	affects binding, increases expression, affects cotreatment, affects expression, decreases expression	8
Curcumin	affects cotreatment, decreases expression, affects expression, decreases reaction, increases expression	7
Doxorubicin	affects response to substance, affects expression, decreases response to substance, affects cotreatment, affects binding (+3 more)	7
Resveratrol	increases reaction, decreases expression, decreases reaction, affects binding	6
Silicon Dioxide	increases expression, increases response to substance	6
sodium arsenite	decreases methylation, affects cotreatment, increases abundance, increases expression, decreases expression	5
(+)-JQ1 compound	decreases expression, affects cotreatment	5
Vorinostat	affects cotreatment, increases expression, decreases expression, decreases reaction	5
Tretinoin	affects cotreatment, decreases expression, increases expression	5
trichostatin A	affects cotreatment, increases expression, affects expression	4
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression, decreases expression	4
Dexamethasone	decreases expression, decreases reaction, increases expression	4
Plant Extracts	affects expression, decreases reaction, increases expression, decreases expression	4
Valproic Acid	affects expression, increases expression	4
Aflatoxin B1	affects expression, increases expression, increases methylation	4
Paclitaxel	decreases reaction, increases expression, decreases expression, affects cotreatment	4
Asbestos, Crocidolite	decreases expression, increases expression, affects expression	4
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases degradation, increases expression	3
SN50 peptide	decreases reaction, increases expression, decreases expression	3
3-(4-methylphenylsulfonyl)-2-propenenitrile	decreases expression	3
Bortezomib	increases expression, increases response to substance, decreases expression	3
Calcitriol	decreases expression, increases expression, affects cotreatment	3
Cisplatin	decreases response to substance, decreases expression, increases expression	3
Etoposide	decreases response to substance, affects cotreatment, decreases expression	3
Folic Acid	affects cotreatment, increases expression, decreases expression, affects expression	3
Lipopolysaccharides	decreases reaction, increases expression, affects expression, affects response to substance, affects cotreatment	3
Tetrachlorodibenzodioxin	increases expression	3
Tetradecanoylphorbol Acetate	affects cotreatment, decreases expression, decreases reaction, increases expression	3

ChEMBL screening assays

119 unique, capped per target: 119 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2439460	Binding	Inhibition of cIAP1/2 in human MDA-MB-231 cells assessed as induction of TNFalpha level at 0.37 to 3.3 uM after 19 hrs by ELISA	Optimization of benzodiazepinones as selective inhibitors of the X-linked inhibitor of apoptosis protein (XIAP) second baculovirus IAP repeat (BIR2) domain. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SF18	HAP1 BIRC3 (-) 1	Cancer cell line	Male
CVCL_SF19	HAP1 BIRC3 (-) 2	Cancer cell line	Male
CVCL_SF20	HAP1 BIRC3 (-) 3	Cancer cell line	Male
CVCL_ZE82	BMA19	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.