XIAP

Summary

XIAP (X-linked inhibitor of apoptosis, HGNC:592) is a protein-coding gene on chromosome Xq25, encoding E3 ubiquitin-protein ligase XIAP (P98170). Multi-functional protein which regulates not only caspases and apoptosis, but also modulates inflammatory signaling and immunity, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. Mutations in this gene are the cause of X-linked lymphoproliferative syndrome. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 2 and 11.

Source: NCBI Gene 331 — RefSeq curated summary.

At a glance

• Gene–disease (curated): X-linked lymphoproliferative disease due to XIAP deficiency (Strong, GenCC)
• Clinical variants (ClinVar): 532 total — 67 pathogenic, 15 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 6 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_001167

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:592
Approved symbol	XIAP
Name	X-linked inhibitor of apoptosis
Location	Xq25
Locus type	gene with protein product
Status	Approved
Aliases	hILP, ILP-1
Ensembl gene	ENSG00000101966
Ensembl biotype	protein_coding
OMIM	300079
Entrez	331

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 13 protein_coding, 6 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000355640, ENST00000371199, ENST00000422098, ENST00000430625, ENST00000468503, ENST00000468691, ENST00000481776, ENST00000496602, ENST00000497640, ENST00000497906, ENST00000698505, ENST00000886905, ENST00000886906, ENST00000886907, ENST00000886908, ENST00000921843, ENST00000951418, ENST00000951419, ENST00000951420, ENST00000951421

RefSeq mRNA: 5 — MANE Select: NM_001167 NM_001167, NM_001204401, NM_001378590, NM_001378591, NM_001378592

CCDS: CCDS14606

Canonical transcript exons

ENST00000371199 — 7 exons

Exon	Start	End
ENSE00001454620	123906988	123913972
ENSE00001649976	123885631	123886539
ENSE00001810722	123860053	123860293
ENSE00003973811	123900493	123900693
ENSE00003973813	123892731	123892773
ENSE00003973814	123888619	123888718
ENSE00003973818	123891238	123891316

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 97.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.8132 / max 171.3050, expressed in 1812 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197467	10.2700	1773
197469	7.7498	1749
197468	2.3751	1394
197466	1.5537	961
197470	1.4561	943
197464	1.0690	508
209799	0.7491	457
197465	0.6261	293
197471	0.5543	302
197472	0.4101	182

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	97.64	gold quality
ileal mucosa	UBERON:0000331	97.51	gold quality
buccal mucosa cell	CL:0002336	97.25	gold quality
left ventricle myocardium	UBERON:0006566	96.79	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.76	gold quality
calcaneal tendon	UBERON:0003701	95.92	gold quality
oviduct epithelium	UBERON:0004804	95.72	gold quality
nasal cavity epithelium	UBERON:0005384	95.41	gold quality
jejunal mucosa	UBERON:0000399	95.29	gold quality
corpus epididymis	UBERON:0004359	95.20	gold quality
jejunum	UBERON:0002115	95.16	gold quality
tibialis anterior	UBERON:0001385	95.00	gold quality
myocardium	UBERON:0002349	94.96	gold quality
colonic epithelium	UBERON:0000397	94.91	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.88	gold quality
corpus callosum	UBERON:0002336	94.83	gold quality
nipple	UBERON:0002030	94.76	gold quality
pylorus	UBERON:0001166	94.75	gold quality
seminal vesicle	UBERON:0000998	94.65	gold quality
upper arm skin	UBERON:0004263	94.64	gold quality
skin of hip	UBERON:0001554	94.63	gold quality
subthalamic nucleus	UBERON:0001906	94.48	gold quality
substantia nigra pars compacta	UBERON:0001965	94.46	gold quality
colonic mucosa	UBERON:0000317	94.43	gold quality
cardia of stomach	UBERON:0001162	94.34	gold quality
superficial temporal artery	UBERON:0001614	94.32	gold quality
dorsal plus ventral thalamus	UBERON:0001897	94.29	gold quality
substantia nigra pars reticulata	UBERON:0001966	94.23	gold quality
penis	UBERON:0000989	94.08	gold quality
renal medulla	UBERON:0000362	94.06	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-CURD-135	yes	3450.51
E-GEOD-124858	no	266.36
E-GEOD-137537	no	3.40
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, CEBPB, GLI2, HIF1A, KAT5, MAZ, NFKB1, NFKB, NR2C2, PARP1, RELA, SMAD2, SMAD3, SMAD4, SP1, SSB, TP53

miRNA regulators (miRDB)

224 targeting XIAP, 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-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-4682	100.00	68.89	1258
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4803	99.98	71.99	3117
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• genomic organization reported; a novel transcript homologous to BIRC4 and expressed solely in the testis was identified (PMID:11597143)
• The anti-apoptotic activity of XIAP is retained upon mutation of both the caspase 3- and caspase 9-interacting sites. (PMID:11927604)
• caspase 3-mediated focal adhesion kinase processing in human ovarian cancer cells: possible regulation by X-linked inhibitor of apoptosis protein (PMID:11972398)
• ILPIP, a novel XIAP-interacting protein acts as a co-factor enhancing XIAP-mediated activation of JNK1 and the caspase-independent protection of XIAP against apoptosis (PMID:12048196)
• XIAP has a role in degrading smac and protecting cells from mitochondial damage (PMID:12121969)
• calpain-mediated XIAP degradation contributes to initiation of apoptosis in normal neutrophils and dysfunction of this regulatory pathway can lead to pathological neutrophil accumulation. (PMID:12121983)
• Smac-penetratin fusion peptide crossed the cellular membrane, bound XIAP and cIAP1, displaced caspase-3 from cytoplasmic aggregates, and enhanced drug-induced caspase action in situ (PMID:12218061)
• 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)
• Reovirus-induced apoptosis involves reduction of cellular XIAP protein levels (PMID:12388702)
• nuclear ribonucleoproteins C1 and C2 are part of the RNP complex that forms on XIAP IRES, the cellular levels of hnRNPC1 and -C2 parallel the activity of XIAP IRES and the overexpression of hnRNPC1-C2 specifically enhanced translation of XIAP IRES (PMID:12482981)
• findings indicate that the levels of XIAP and Bcl-X(L) are regulated by distinct pathways during monocytic differentiation, and that upregulation of these proteins contributes to the increased longevity of cells in the monocytic lineage (PMID:12592339)
• the overexpression of XIAP inhibits taxol-induced apoptosis through the decrease of caspase-3 activity and inhibition of the processing of pro-caspase-3. (PMID:12624662)
• RING domain was essentially required for the proteasomal association of XIAP and for its ubiquitination. (PMID:12691733)
• Expression of XIAP and downregulation of Fas-L are linked to chemoresistance in ovarian carcinoma cells and may represent one of the potential antiapoptotic mechanisms involved during this process. (PMID:12725530)
• identification of ubiquitination sites (PMID:12747801)
• identification as substrate for mitochondrial serine protease Omi/HtrA2 (PMID:12835328)
• although cIAP-1, cIAP-2 and XIAP transcripts were highly upregulated, their expression of endogenous proteins were not increased in HUVECs stimulated with LPS (PMID:12851723)
• XIAP protein has a role in preventing apoptosis in human lung cancer cells (PMID:12855663)
• cytokines regulate the expression of XIAP in leukemic cell lines and primary AML blasts (PMID:12970762)
• role in relief of caspase inhibition mediated by Smac (PMID:14512414)
• XIAP is regulated by Smac3, a Smac/DIABLO splicing variant (PMID:14523016)
• XIAP is a principal inhibitor of apoptosis overexpressed in human hepatocellular carcinoma and that XIAP may be a potential target for gene therapy of human HCCs (PMID:14532997)
• Grim promoted XIAP ubiquitination and degradation. (PMID:14570909)
• XIAP interacts with CHEK1 during mitosis. (PMID:14759516)
• Data suggest that ARTS induces apoptosis by antagonizing IAPs, including XIAP. (PMID:15029247)
• no difference was observed in XIAP expression between young and aged subjects. (PMID:15037009)
• XIAP up-regulation requires nuclear factor kappa b and has a role in Cyr61-induced resistance to apoptosis in breast cancer cells (PMID:15044484)
• x-linked inhibitor of apoptosis protein and survivin have roles in progression of childhood de novo acute myeloid leukemia (PMID:15173080)
• role of antagonizing XIAP in induction of caspase-dependent cell death in concert with authocatalytic processing of HtrA2/Omi (PMID:15201285)
• First evidence is provided that increased XIAP levels protect the neonatal brain of transgenic XIAP-overexpressing mice against hypoxia-ischemia. (PMID:15207275)
• These data demonstrate that full-length X-linked inhibitor of apoptosis (XIAP) inhibits caspase activation required for mitochondrial amplification of death receptor signals. (PMID:15282301)
• ERK suppresses stress-induced apoptosis downstream of mitochondrial alterations by maintaining XIAP levels and oxidants block this effect through activation of p38 and protein phosphatases (PMID:15292176)
• XIAP-mediated inhibition of apoptosis has a role during progression of clear-cell clear cell renal carcinomas.XIAP expression is a new independent prognostic marker in this tumor type. (PMID:15297970)
• Data indicate that phenylurea-based XIAP antagonists block interaction of downstream effector caspases with XIAP, thus inducing apoptosis of tumor cell lines through a caspase-dependent, Bcl-2/Bax-independent mechanism. (PMID:15337764)
• In drug-induced apoptosis XIAP & its BIR3-RING cleavage product redistribute into large nuclear inclusions, implying a new unknown function of XIAP and its BIR3-RING fragment. (PMID:15359644)
• Treatment with rottlerin downregulated the protein levels of survivin and X-chromosome-linked IAP (XIAP), two major caspase inhibitors. (PMID:15531913)
• The XIAP expression was significantly lower in patients with favorable than intermediate or poor cytogenetics (n = 74; P < 0.05). (PMID:15570290)
• XIAP binds directly to the active-site pockets of effector caspases (PMID:15580265)
• Genetically modified human islets expressing XIAP are resistant to the negative effects of immunosuppressive drugs on insulin secretion and cell viability. (PMID:15677500)
• XIAP functions as ubiquitin ligase toward mature caspase-9 and Smac to inhibit apoptosis. (PMID:15749826)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	xiap	ENSDARG00000016143
mus_musculus	Xiap	ENSMUSG00000025860
rattus_norvegicus	Xiap	ENSRNOG00000006967
drosophila_melanogaster	Diap2	FBGN0015247
caenorhabditis_elegans		WBGENE00000250

Paralogs (7): BIRC3 (ENSG00000023445), BIRC5 (ENSG00000089685), NLRC4 (ENSG00000091106), BIRC7 (ENSG00000101197), BIRC2 (ENSG00000110330), BIRC6 (ENSG00000115760), NAIP (ENSG00000249437)

Protein

Protein identifiers

E3 ubiquitin-protein ligase XIAP — P98170 (reviewed: P98170)

Alternative names: Baculoviral IAP repeat-containing protein 4, IAP-like protein, Inhibitor of apoptosis protein 3, RING-type E3 ubiquitin transferase XIAP, X-linked inhibitor of apoptosis protein

All UniProt accessions (3): P98170, B1AKU2, B1AKU3

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, copper homeostasis, mitogenic kinase signaling, cell proliferation, as well as cell invasion and metastasis. Acts as a direct caspase inhibitor. Directly bind to the active site pocket of CASP3 and CASP7 and obstructs substrate entry. Inactivates CASP9 by keeping it in a monomeric, inactive state. Acts as an E3 ubiquitin-protein ligase regulating NF-kappa-B signaling and the target proteins for its E3 ubiquitin-protein ligase activity include: RIPK1, RIPK2, MAP3K2/MEKK2, DIABLO/SMAC, AIFM1, CCS, PTEN and BIRC5/survivin. Acts as an important regulator of innate immunity by mediating ‘Lys-63’-linked polyubiquitination of RIPK2 downstream of NOD1 and NOD2, thereby transforming RIPK2 into a scaffolding protein for downstream effectors, ultimately leading to activation of the NF-kappa-B and MAP kinases signaling. ‘Lys-63’-linked polyubiquitination of RIPK2 also promotes recruitment of the LUBAC complex to RIPK2. Regulates the BMP signaling pathway and the SMAD and MAP3K7/TAK1 dependent pathways leading to NF-kappa-B and JNK activation. Ubiquitination of CCS leads to enhancement of its chaperone activity toward its physiologic target, SOD1, rather than proteasomal degradation. Ubiquitination of MAP3K2/MEKK2 and AIFM1 does not lead to proteasomal degradation. Plays a role in copper homeostasis by ubiquitinating COMMD1 and promoting its proteasomal degradation. Can also function as E3 ubiquitin-protein ligase of the NEDD8 conjugation pathway, targeting effector caspases for neddylation and inactivation. Ubiquitinates and therefore mediates the proteasomal degradation of BCL2 in response to apoptosis. Protects cells from spontaneous formation of the ripoptosome, a large multi-protein complex that has the capability to kill cancer cells in a caspase-dependent and caspase-independent manner. Suppresses ripoptosome formation by ubiquitinating RIPK1 and CASP8. Acts as a positive regulator of Wnt signaling and ubiquitinates TLE1, TLE2, TLE3, TLE4 and AES. Ubiquitination of TLE3 results in inhibition of its interaction with TCF7L2/TCF4 thereby allowing efficient recruitment and binding of the transcriptional coactivator beta-catenin to TCF7L2/TCF4 that is required to initiate a Wnt-specific transcriptional program.

Subunit / interactions. Monomer, and homodimer. Part of a complex composed of SEPTIN4 isoform ARTS, XIAP and BCL2, within the complex interacts with SEPTIN4 isoform ARTS and BCL2, SEPTIN4 isoform ARTS acts as a scaffold protein and stabilizes the complex. Interacts (via BIR3 domain) with DIABLO/SMAC; the interaction inhibits apoptotic suppressor activity. Interacts with HTRA2/PRSS25; the interaction inhibits apoptotic suppressor activity. Interacts with TAB1/MAP3K7IP1 and AIFM1. Interaction with DIABLO/SMAC hinders binding of TAB1/MAP3K7IP1 and AIFM1. Interacts with TCF25 and COMMD1. Interacts (via BIR3 domain) with SEPTIN4 isoform ARTS. Interacts (via BIR3 domain) with SEPTIN4. Interacts with RIP1, RIP2, RIP3, RIP4, CCS and USP19. Interacts (via BIR 2 domain and BIR 3 domain) with HAX1 (via C-terminus) and this interaction blocks ubiquitination of XIAP/BIRC4. Interacts with the monomeric form of BIRC5/survivin. Interacts with TLE3 and TCF7L2/TCF4. Interacts (via BIR 3 and RING domains) with PDCL3.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. Expressed in colonic crypts (at protein level). Ubiquitous, except peripheral blood leukocytes.

Post-translational modifications. S-Nitrosylation down-regulates its E3 ubiquitin-protein ligase activity. Autoubiquitinated. Ubiquitinated by TRIM32; leading to proteasomal degradation.

Disease relevance. Lymphoproliferative syndrome, X-linked, 2 (XLP2) [MIM:300635] A rare immunodeficiency characterized by extreme susceptibility to infection with Epstein-Barr virus (EBV). Symptoms include severe or fatal mononucleosis, acquired hypogammaglobulinemia, pancytopenia and malignant lymphoma. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The first BIR domain is involved in interaction with TAB1/MAP3K7IP1 and is important for dimerization. The second BIR domain is sufficient to inhibit CASP3 and CASP7, while the third BIR is involved in CASP9 inhibition. The interactions with DIABLO/SMAC and HTRA2/PRSS25 are mediated by the second and third BIR domains.

Similarity. Belongs to the IAP family.

RefSeq proteins (5): NP_001158, NP_001191330, NP_001365519, NP_001365520, NP_001365521 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001370	BIR_rpt	Repeat
IPR001841	Znf_RING	Domain
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR042579	XIAP/BIRC8_UBA	Domain
IPR048875	BIRC2-3-like_UBA	Domain
IPR050784	IAP	Family

Pfam: PF00653, PF13920, PF21290

UniProt features (108 total): helix 28, mutagenesis site 23, strand 17, sequence variant 13, turn 10, binding site 4, region of interest 4, repeat 3, cross-link 2, chain 1, modified residue 1, zinc finger region 1, sequence conflict 1

Structure

Experimental structures (PDB)

74 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4J44	X-RAY DIFFRACTION	1.3
8W59	X-RAY DIFFRACTION	1.34
4J47	X-RAY DIFFRACTION	1.35
4J46	X-RAY DIFFRACTION	1.42
4J3Y	X-RAY DIFFRACTION	1.45
4J45	X-RAY DIFFRACTION	1.48
5O6T	X-RAY DIFFRACTION	1.57
4KJU	X-RAY DIFFRACTION	1.6
8W5A	X-RAY DIFFRACTION	1.65
4KJV	X-RAY DIFFRACTION	1.7
3UW5	X-RAY DIFFRACTION	1.71
8GH7	X-RAY DIFFRACTION	1.75
4IC3	X-RAY DIFFRACTION	1.78
3UW4	X-RAY DIFFRACTION	1.79
2POI	X-RAY DIFFRACTION	1.8
3HL5	X-RAY DIFFRACTION	1.8
6GJW	X-RAY DIFFRACTION	1.9
4KMP	X-RAY DIFFRACTION	1.95
4WVT	X-RAY DIFFRACTION	1.96
1G73	X-RAY DIFFRACTION	2
4WVU	X-RAY DIFFRACTION	2.02
5C3K	X-RAY DIFFRACTION	2.02
6H6R	X-RAY DIFFRACTION	2.03
4WVS	X-RAY DIFFRACTION	2.09
2VSL	X-RAY DIFFRACTION	2.1
4J48	X-RAY DIFFRACTION	2.1
4MTZ	X-RAY DIFFRACTION	2.1
4IC2	X-RAY DIFFRACTION	2.2
5C0K	X-RAY DIFFRACTION	2.2
5C7D	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P98170-F1	74.60	0.31

Functional residue map

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

Ligand- & substrate-binding residues (4): 303; 320; 327; 300

Post-translational modifications (3): 450, 322, 328

Mutagenesis-validated functional residues (23):

Position	Phenotype
75	loss of interaction with tab1/map3k7ip1; when associated with g-75.
80	strongly reduced interaction with tab1/map3k7ip1. reduced activation of map3k7/tak1. reduced activation of nf-kappa-b.
80	loss of interaction with tab1/map3k7ip1. reduced activation of map3k7/tak1. strongly reduced activation of nf-kappa-b.
86	loss of dimerization. reduces activation of nf-kappa-b.
87	no effect on dimerization.
87	abolishes dimerization. interferes with ubiquitination.
98	loss of interaction with tab1/map3k7ip1; when associated with g-75.
141	reduced inhibition of caspase-3.
147	reduced inhibition of caspase-3.
148	abolishes inhibition of caspase-3. reduced interaction with htra2; when associated with s-214.
149	reduced inhibition of caspase-3.
151	reduced inhibition of caspase-3.
167	reduced inhibition of caspase-3.
196	reduced inhibition of caspase-3. may affect protein folding and stability.
214	reduced interaction with htra2. reduced interaction with htra2; when associated with a-148.
259	reduced interaction with htra2; when associated with s-314.
310	no effect on interaction with septin4 isoform arts.
310	reduced interaction with htra2; when associated with s-314.
314	decreased interaction with diablo/smac and with htra2. decreases interaction with htra2; when associated with d-259 or a
343	no effect on interaction with septin4 isoform arts.
450	inhibits degradation of active caspase-3.
467	loss of e3 ubiquitin-protein ligase activity.
495	abolished e3 ubiquitin-protein ligase activity and ability to ubiquitinate ripk2.

Function

Pathways and Gene Ontology

Reactome pathways

14 pathways

ID	Pathway
R-HSA-111459	Activation of caspases through apoptosome-mediated cleavage
R-HSA-111463	SMAC (DIABLO) binds to IAPs
R-HSA-111464	SMAC(DIABLO)-mediated dissociation of IAP:caspase complexes
R-HSA-111469	SMAC, XIAP-regulated apoptotic response
R-HSA-3769402	Deactivation of the beta-catenin transactivating complex
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-5675482	Regulation of necroptotic cell death
R-HSA-8948747	Regulation of PTEN localization
R-HSA-8948751	Regulation of PTEN stability and activity
R-HSA-9627069	Regulation of the apoptosome activity
R-HSA-9958825	Activation of STAT3 by cadherin engagement

MSigDB gene sets: 453 (showing top): GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, TGCGCANK_UNKNOWN, GOBP_POSITIVE_REGULATION_OF_TYPE_I_INTERFERON_PRODUCTION, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_NUCLEOTIDE_BINDING_DOMAIN_LEUCINE_RICH_REPEAT_CONTAINING_RECEPTOR_SIGNALING_PATHWAY, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOBP_POSITIVE_REGULATION_OF_CYTOKINE_PRODUCTION, GOBP_NEGATIVE_REGULATION_OF_TUMOR_NECROSIS_FACTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, RIZKI_TUMOR_INVASIVENESS_3D_DN, WEI_MYCN_TARGETS_WITH_E_BOX, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS

GO Biological Process (33): DNA damage response (GO:0006974), negative regulation of tumor necrosis factor-mediated signaling pathway (GO:0010804), Wnt signaling pathway (GO:0016055), quinolinate biosynthetic process (GO:0019805), regulation of BMP signaling pathway (GO:0030510), positive regulation of protein ubiquitination (GO:0031398), positive regulation of type I interferon production (GO:0032481), response to lipopolysaccharide (GO:0032496), defense response to bacterium (GO:0042742), 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), positive regulation of JNK cascade (GO:0046330), regulation of inflammatory response (GO:0050727), neuron apoptotic process (GO:0051402), regulation of cell cycle (GO:0051726), copper ion homeostasis (GO:0055070), regulation of apoptosis involved in tissue homeostasis (GO:0060785), regulation of nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway (GO:0070424), nucleotide-binding oligomerization domain containing 1 signaling pathway (GO:0070427), nucleotide-binding oligomerization domain containing 2 signaling pathway (GO:0070431), protein K63-linked ubiquitination (GO:0070534), positive regulation of canonical Wnt signaling pathway (GO:0090263), positive regulation of protein linear polyubiquitination (GO:1902530), ubiquitin-dependent protein catabolic process (GO:0006511), apoptotic process (GO:0006915), canonical NF-kappaB signal transduction (GO:0007249), negative regulation of type I interferon production (GO:0032480), p38MAPK cascade (GO:0038066), negative regulation of canonical NF-kappaB signal transduction (GO:0043124), protein linear polyubiquitination (GO:0097039), execution phase of apoptosis (GO:0097194)

GO Molecular Function (11): ubiquitin-protein transferase activity (GO:0004842), cysteine-type endopeptidase inhibitor activity (GO:0004869), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), cysteine-type endopeptidase inhibitor activity involved in apoptotic process (GO:0043027), ubiquitin protein ligase activity (GO:0061630), protein serine/threonine kinase binding (GO:0120283), protein binding (GO:0005515), transferase activity (GO:0016740), peptidase inhibitor activity (GO:0030414), metal ion binding (GO:0046872)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
TNF signaling	3
SMAC, XIAP-regulated apoptotic response	2
PTEN Regulation	2
Cytochrome c-mediated apoptotic response	1
Apoptotic factor-mediated response	1
TCF dependent signaling in response to WNT	1
Regulated Necrosis	1
RIPK1-mediated regulated necrosis	1
Formation of apoptosome	1
Adherens junctions interactions	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
apoptotic process	3
cellular anatomical structure	3
regulation of apoptotic process	2
regulation of defense response	2
regulation of response to external stimulus	2
cellular response to stress	1
negative regulation of cytokine-mediated signaling pathway	1
regulation of tumor necrosis factor-mediated signaling pathway	1
tumor necrosis factor-mediated signaling pathway	1
cell surface receptor signaling pathway	1
dicarboxylic acid biosynthetic process	1
quinolinate metabolic process	1
pyridine-containing compound biosynthetic process	1
BMP signaling pathway	1
regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
regulation of cellular response to growth factor stimulus	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
positive regulation of cytokine production	1
regulation of type I interferon production	1
type I interferon production	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
defense response	1
response to bacterium	1
regulation of programmed cell death	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
JNK cascade	1
positive regulation of MAPK cascade	1
regulation of JNK cascade	1
inflammatory response	1
cell cycle	1

Protein interactions and networks

STRING

4100 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
XIAP	DIABLO	Q9NR28	999
XIAP	CASP3	P42574	998
XIAP	CASP9	P55211	998
XIAP	XAF1	Q6GPH4	997
XIAP	CASP7	P55210	997
XIAP	TAB1	Q15750	992
XIAP	CASP1	P29466	959
XIAP	BCL2L1	Q07817	936
XIAP	BCL2	P10415	933
XIAP	HTRA2	O43464	923
XIAP	TRAF1	Q13077	914
XIAP	RIPK2	O43353	911
XIAP	CASP8	Q14790	910
XIAP	CFLAR	O15519	896
XIAP	APAF1	O14727	896

IntAct

419 interactions, top by confidence:

A	B	Type	Score
CASP9	XIAP	psi-mi:“MI:0915”(physical association)	0.970
CASP9	XIAP	psi-mi:“MI:0407”(direct interaction)	0.970
XIAP	CASP9	psi-mi:“MI:0915”(physical association)	0.970
XIAP	CASP9	psi-mi:“MI:2364”(proximity)	0.970
CASP9	XIAP	psi-mi:“MI:2364”(proximity)	0.970
RIPK2	XIAP	psi-mi:“MI:0915”(physical association)	0.950
XIAP	RIPK2	psi-mi:“MI:0915”(physical association)	0.950
XIAP	RIPK2	psi-mi:“MI:0914”(association)	0.950

BioGRID (733): DIABLO (Affinity Capture-Western), XIAP (Biochemical Activity), UBE2N (Reconstituted Complex), UBE2D1 (Reconstituted Complex), UBE2D2 (Reconstituted Complex), UBE2E1 (Reconstituted Complex), UBE2D3 (Reconstituted Complex), RAC1 (Affinity Capture-Western), RAC1 (Affinity Capture-Luminescence), XIAP (Affinity Capture-Western), CASP9 (Two-hybrid), CASP10 (Two-hybrid), CKS1B (Two-hybrid), ERCC3 (Two-hybrid), RFC5 (Two-hybrid)

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

38 interactions.

A	Effect	B	Mechanism
XIAP	“down-regulates quantity by destabilization”	CASP9	binding
XIAP	“down-regulates quantity by destabilization”	CASP3	ubiquitination
DIABLO	“down-regulates activity”	XIAP	binding
HTRA2	down-regulates	XIAP	binding
XIAP	“down-regulates activity”	CASP3	binding
DIABLO	“down-regulates quantity”	XIAP	binding
AKT1	“up-regulates quantity by stabilization”	XIAP	phosphorylation
AKT2	up-regulates	XIAP	phosphorylation
BIRC5	up-regulates	XIAP	binding
XAF1	down-regulates	XIAP	binding
DIABLO	down-regulates	XIAP	binding
AKT	“up-regulates quantity by stabilization”	XIAP	phosphorylation
embelin	“down-regulates activity”	XIAP	“chemical inhibition”
Ub:E2	“up-regulates activity”	XIAP	ubiquitination
XIAP	“up-regulates activity”	RIPK4	polyubiquitination
GSK3B	“up-regulates activity”	XIAP	phosphorylation
XIAP	“up-regulates activity”	TLE3	ubiquitination
XIAP	“down-regulates quantity by destabilization”	AIFM1	ubiquitination
XIAP	“up-regulates activity”	HIF1A	ubiquitination
XIAP	“down-regulates quantity”	PTEN	ubiquitination
XIAP	“down-regulates quantity”	CDC42	ubiquitination
XIAP	“down-regulates quantity”	OGT	ubiquitination
XIAP	“down-regulates quantity”	SEPTIN4	ubiquitination
RAF1	“up-regulates activity”	XIAP	phosphorylation
hsa-mir-431-5p	“down-regulates quantity by repression”	XIAP	“post transcriptional regulation”
hsa-mir-186-5p	“down-regulates quantity by repression”	XIAP	“post transcriptional regulation”
hsa-mir23a3p	“down-regulates quantity by repression”	XIAP	“post transcriptional regulation”
hsa-mir-149-5p	“down-regulates quantity by repression”	XIAP	“post transcriptional regulation”
hsa-mir-519d-3p	“down-regulates quantity by repression”	XIAP	“post transcriptional regulation”
XIAP	“up-regulates activity”	RIPK2	ubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 97 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	55.5×	2e-07
IKK complex recruitment mediated by RIP1	6	45.8×	3e-07
JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1	5	39.9×	5e-06
activated TAK1 mediates p38 MAPK activation	5	38.2×	6e-06
NOD1/2 Signaling Pathway	7	34.2×	2e-07
Synthesis of active ubiquitin: roles of E1 and E2 enzymes	6	34.0×	1e-06
TAK1-dependent IKK and NF-kappa-B activation	5	23.1×	8e-05
E3 ubiquitin ligases ubiquitinate target proteins	7	20.8×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
protein K11-linked ubiquitination	5	23.6×	2e-04
protein monoubiquitination	5	20.7×	3e-04
protein modification process	6	17.7×	1e-04
protein K48-linked ubiquitination	8	16.2×	7e-06
protein K63-linked ubiquitination	5	16.1×	9e-04
protein polyubiquitination	10	13.9×	8e-07
positive regulation of protein ubiquitination	5	12.8×	2e-03
neuron apoptotic process	5	11.2×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	67
Likely pathogenic	15
Uncertain significance	178
Likely benign	75
Benign	81

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1071347	NM_001167.4(XIAP):c.1012dup (p.Tyr338fs)	Pathogenic
1072889	NM_001167.4(XIAP):c.978-2A>G	Pathogenic
1073250	NM_001167.4(XIAP):c.60del (p.Glu21fs)	Pathogenic
1162913	NM_001167.4(XIAP):c.894_898del (p.Lys299fs)	Pathogenic
11645	NM_001167.4(XIAP):c.292del (p.Glu99fs)	Pathogenic
11646	NM_001167.4(XIAP):c.352G>T (p.Glu118Ter)	Pathogenic
11647	NG_007264.1:g.(31343_33421)_(33522_36040)del	Pathogenic
1375770	NM_001167.4(XIAP):c.755dup (p.Asn252fs)	Pathogenic
1418323	NM_001167.4(XIAP):c.1315G>T (p.Glu439Ter)	Pathogenic
1452964	NM_001167.4(XIAP):c.921_924del (p.Thr308fs)	Pathogenic
1456269	NM_001167.4(XIAP):c.1048G>T (p.Glu350Ter)	Pathogenic
1482523	NM_001167.4(XIAP):c.1386del (p.Phe462fs)	Pathogenic
1701610	NM_001167.4(XIAP):c.345C>G (p.Tyr115Ter)	Pathogenic
2019044	NM_001167.4(XIAP):c.990_991del (p.Leu331fs)	Pathogenic
2048465	NM_001167.4(XIAP):c.1009G>T (p.Glu337Ter)	Pathogenic
2138713	NM_001167.4(XIAP):c.145C>T (p.Arg49Ter)	Pathogenic
2700917	NM_001167.4(XIAP):c.664_665insTGTC (p.Arg222fs)	Pathogenic
2836709	NM_001167.4(XIAP):c.371del (p.Arg124fs)	Pathogenic
2867274	NM_001167.4(XIAP):c.481del (p.Tyr161fs)	Pathogenic
3068635	NM_001167.4(XIAP):c.985del (p.Tyr329fs)	Pathogenic
3244551	NC_000023.10:g.(?123010866)(123025086_?)del	Pathogenic
3244562	NC_000023.10:g.(?123025068)(123041031_?)del	Pathogenic
3255350	NM_001167.4(XIAP):c.969G>A (p.Trp323Ter)	Pathogenic
3255351	NM_001167.4(XIAP):c.1057-600_1300+79del	Pathogenic
3337747	NM_001167.4(XIAP):c.1057-2A>G	Pathogenic
3642311	NM_001167.4(XIAP):c.218G>A (p.Trp73Ter)	Pathogenic
3645202	NM_001167.4(XIAP):c.568dup (p.Tyr190fs)	Pathogenic
3653116	NM_001167.4(XIAP):c.416_417del (p.Tyr139fs)	Pathogenic
3663962	NM_001167.4(XIAP):c.764dup (p.Asn255fs)	Pathogenic
3664415	NM_001167.4(XIAP):c.64G>T (p.Glu22Ter)	Pathogenic

SpliceAI

1031 predictions. Top by Δscore:

Variant	Effect	Δscore
X:123859901:AAGTG:A	donor_gain	1.0000
X:123859903:GTG:G	donor_gain	1.0000
X:123859904:TG:T	donor_gain	1.0000
X:123859905:GG:G	donor_gain	1.0000
X:123859905:GGT:G	donor_loss	1.0000
X:123859906:G:GG	donor_gain	1.0000
X:123859907:T:A	donor_loss	1.0000
X:123885629:A:AG	acceptor_gain	1.0000
X:123885630:G:GG	acceptor_gain	1.0000
X:123885630:GAAAA:G	acceptor_gain	1.0000
X:123885720:G:GT	donor_gain	1.0000
X:123888614:C:CA	acceptor_gain	1.0000
X:123888615:GTA:G	acceptor_loss	1.0000
X:123888616:TAG:T	acceptor_loss	1.0000
X:123888617:A:AG	acceptor_gain	1.0000
X:123888617:A:T	acceptor_loss	1.0000
X:123888617:AGGT:A	acceptor_gain	1.0000
X:123888618:G:A	acceptor_loss	1.0000
X:123888618:G:GA	acceptor_gain	1.0000
X:123888618:GGT:G	acceptor_gain	1.0000
X:123888618:GGTG:G	acceptor_gain	1.0000
X:123888618:GGTGA:G	acceptor_gain	1.0000
X:123888715:CAGG:C	donor_loss	1.0000
X:123888717:GG:G	donor_gain	1.0000
X:123888718:GG:G	donor_gain	1.0000
X:123888718:GGTA:G	donor_loss	1.0000
X:123888719:G:GC	donor_loss	1.0000
X:123888719:G:GG	donor_gain	1.0000
X:123888720:T:A	donor_loss	1.0000
X:123891232:GTTTA:G	acceptor_loss	1.0000

AlphaMissense

3298 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:123907128:T:C	C481R	0.999
X:123886292:G:C	W210C	0.998
X:123886292:G:T	W210C	0.998
X:123907035:T:A	C450S	0.998
X:123907035:T:C	C450R	0.998
X:123907036:G:C	C450S	0.998
X:123885817:T:C	F52S	0.997
X:123885879:T:A	W73R	0.997
X:123885879:T:C	W73R	0.997
X:123886290:T:A	W210R	0.997
X:123886290:T:C	W210R	0.997
X:123886525:G:A	G288E	0.997
X:123888639:T:C	C300R	0.997
X:123907036:G:A	C450Y	0.997
X:123907128:T:A	C481S	0.997
X:123907129:G:C	C481S	0.997
X:123885814:G:A	G51E	0.996
X:123885849:T:C	C63R	0.996
X:123886160:A:C	R166S	0.996
X:123886160:A:T	R166S	0.996
X:123886225:G:A	G188E	0.996
X:123886260:T:C	C200R	0.996
X:123907037:C:G	C450W	0.996
X:123907044:T:C	C453R	0.996
X:123907088:T:A	H467Q	0.996
X:123907088:T:G	H467Q	0.996
X:123907098:T:C	C471R	0.996
X:123907107:T:A	C474S	0.996
X:123907107:T:C	C474R	0.996
X:123907108:G:C	C474S	0.996

dbSNP variants (sampled 300 via entrez): RS1000178313 (X:123883072 G>A), RS1000288896 (X:123874676 A>G), RS1000357784 (X:123892094 G>A), RS1000448604 (X:123867010 G>A), RS1000458695 (X:123882806 G>A,T), RS1000574467 (X:123858005 A>G,T), RS1000753522 (X:123866640 T>C), RS1000774226 (X:123875047 A>G), RS1000825451 (X:123897626 G>A), RS1000896013 (X:123863076 T>C), RS1001003044 (X:123876703 T>G), RS1001008788 (X:123858263 C>T), RS1001041898 (X:123876113 A>G), RS1001435900 (X:123890557 G>A), RS1001465918 (X:123865454 G>A)

Disease associations

OMIM: gene MIM:300079 | disease phenotypes: MIM:300635, MIM:308240, MIM:300751, MIM:615122

GenCC curated gene-disease

Disease	Classification	Inheritance
X-linked lymphoproliferative disease due to XIAP deficiency	Strong	X-linked

Mondo (5): X-linked lymphoproliferative disease due to XIAP deficiency (MONDO:0010385), autoinflammatory syndrome (MONDO:0019751), X-linked lymphoproliferative disease due to SH2D1A deficiency (MONDO:0024551), X-linked sideroblastic anemia 1 (MONDO:0020721), lymphoproliferative syndrome 2 (MONDO:0014054)

Orphanet (6): X-linked lymphoproliferative disease (Orphanet:2442), X-linked lymphoproliferative disease due to XIAP deficiency (Orphanet:538934), Autoinflammatory syndrome (Orphanet:93665), X-linked lymphoproliferative disease due to SAP deficiency (Orphanet:538931), X-linked sideroblastic anemia (Orphanet:75563), Combined immunodeficiency due to CD27 deficiency (Orphanet:238505)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000083	Renal insufficiency
HP:0000123	Nephritis
HP:0000554	Uveitis
HP:0001061	Acne
HP:0001287	Meningitis
HP:0001369	Arthritis
HP:0001399	Hepatic failure
HP:0001417	X-linked inheritance
HP:0001419	X-linked recessive inheritance
HP:0001581	Recurrent skin infections
HP:0001744	Splenomegaly
HP:0001873	Thrombocytopenia
HP:0001875	Decreased total neutrophil count
HP:0001876	Pancytopenia
HP:0001915	Aplastic anemia
HP:0001945	Fever
HP:0001954	Recurrent fever
HP:0002037	Inflammation of the large intestine
HP:0002155	Hypertriglyceridemia
HP:0002205	Recurrent respiratory infections
HP:0002240	Hepatomegaly
HP:0002383	Infectious encephalitis
HP:0002480	Hepatic encephalopathy
HP:0002583	Colitis
HP:0002633	Vasculitis
HP:0002665	Lymphoma
HP:0002716	Lymphadenopathy
HP:0002719	Recurrent infections
HP:0002721	Immunodeficiency
HP:0002961	Dysgammaglobulinemia

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C564469	Lymphoproliferative Syndrome, X-Linked, 2 (supp.)
C536761	X-linked sideroblastic anemia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (22): CHEMBL4198 (SINGLE PROTEIN), CHEMBL4296120 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523721 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523722 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523723 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630750 (PROTEIN-PROTEIN INTERACTION), CHEMBL4630751 (PROTEIN-PROTEIN INTERACTION), CHEMBL4888447 (PROTEIN-PROTEIN INTERACTION), CHEMBL5291968 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465212 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

6 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 534,439 (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
CHEMBL301523	PHENYLALANINE	3	530,828
CHEMBL2431768	LCL-161	2	1,365
CHEMBL3039522	BIRINAPANT	2	925
CHEMBL2063869	GDC-0152	1	281
CHEMBL4173974	ASTX-660	1	360

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 (10 total), top 10:

Ligand	Action	Affinity	Parameter
BV-6	Inhibition	8.89	pKd
tolinapant	Inhibition	8.55	pIC50
AZD5582	Antagonist	7.82	pIC50
SM-337	Antagonist	7.59	pKi
SM-122	Inhibition	7.59	pKi
GDC-0152	Antagonist	7.55	pKi
LCL161	Inhibition	7.52	pIC50
compound 20 [PMID: 34432979]	Binding	7.4	pIC50
birinapant	Antagonist	7.35	pKd
xevinapant	Antagonist	7.18	pKi

Binding affinities (BindingDB)

1256 measured of 1387 human assays (1654 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(2S)-3-[4-[[4-[[(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]phenyl]methoxy]phenyl]-2-[[(2S)-2-(methylamino)propanoyl]amino]propanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,6-dihydro-2H-pyridine-2-carboxamide	IC50	0.22 nM	US-9453048: IAP antagonists
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
1-[(2S)-3-[4-[[4-[[(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]phenyl]methoxy]phenyl]-2-[[(2S)-2-(methylamino)propanoyl]amino]propanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]piperidine-2-carboxamide	IC50	0.46 nM	US-9453048: IAP antagonists
(4S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-4-[[4-[[4-[2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxo-3-[(6S)-6-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)cyclohex-3-en-1-yl]propyl]phenoxy]methyl]benzoyl]amino]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide	IC50	0.48 nM	US-9453048: IAP antagonists
(2S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-4-[[4-[[4-[(2S)-2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxo-3-[2-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]carbamoyl]pyrrolidin-1-yl]propyl]phenoxy]methyl]benzoyl]amino]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxamide	IC50	0.49 nM	US-9453048: IAP antagonists
(4S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-4-[[4-[[4-[2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxo-3-[(2S)-2-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)cyclohexyl]propyl]phenoxy]methyl]benzoyl]amino]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide	IC50	0.62 nM	US-9453048: IAP antagonists
(2S,4S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-4-[[4-[[4-[2-[[(2S)-2-(methylamino)propanoyl]amino]-3-oxo-3-[(6R)-6-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)cyclohex-3-en-1-yl]propyl]phenoxy]methyl]benzoyl]amino]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)pyrrolidine-2-carboxamide	IC50	0.72 nM	US-9453048: IAP antagonists
(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)-N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(1-methylindazol-5-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(8-fluoro-2-methylquinolin-4-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(3-methylimidazo[1,5-a]pyridin-7-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-4-(1-methylpyrazolo[4,5-d]pyrimidin-7-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-4-(1-methylpyrazolo[4,5-d]pyrimidin-7-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-N-[4-(2,3-dimethylimidazo[1,2-a]pyridin-5-yl)-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[4-(5-methylimidazo[1,2-a]pyridin-3-yl)-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-4-(1,2,4,6-tetramethyl-3-oxopyrazolo[4,3-c]pyridin-7-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-4-(1,3,5-trimethylpyrazolo[4,5-d]pyrimidin-7-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-4-(1,3,5-trimethylpyrazolo[4,5-d]pyrimidin-7-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methylindazol-5-yl)ethynyl]-4-(1,3,5-trimethylpyrazolo[4,5-d]pyrimidin-7-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-4-(2,3,6-trimethylpyrazolo[3,4-d]pyrimidin-4-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-(1-methylindazol-5-yl)ethynyl]-4-(2,3,6-trimethylpyrazolo[3,4-d]pyrimidin-4-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-[2-[2-(4-methylimidazol-1-yl)pyrimidin-5-yl]ethynyl]-4-(2,3,6-trimethylpyrazolo[3,4-d]pyrimidin-4-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(2R)-2-(methylamino)-N-[6-(2-thiophen-2-ylethynyl)-4-(2,3,6-trimethylpyrazolo[3,4-d]pyrimidin-4-yl)-2-pyridinyl]propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(2-methylquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(2,6-dimethyl-4-pyridinyl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
N-[6-[2-(3,5-difluorophenyl)ethynyl]-4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-[4-(4-methylimidazol-1-yl)phenyl]ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(8-fluoroquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
N-[4-(1,3-dimethylpyrazolo[4,5-d]pyrimidin-7-yl)-6-[2-(1-methylpyrazolo[5,4-b]pyridin-5-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9278978: 6-Alkynyl Pyridine
(S)—N—((S)-5-(4-Acetylbenzoyl)-1-((6-bromo-2-methoxynaphthalen-1-yl)methyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b][1,4]diazepin-3-yl)-2-(methylamino)butanamide hydrochloride	IC50	1 nM	US-10053431: Tetrahydro-benzodiazepinones
(2S)-N-[5-[2-(2-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(3-methylimidazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(6-methyl-3-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[6-[2-(1-methylisoquinolin-6-yl)ethynyl]-5-[7-methyl-2-(2-methylpyrimidin-5-yl)imidazo[1,2-a]pyridin-3-yl]-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-4-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(6-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methylisoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-2-(methylamino)-N-[5-[7-methyl-2-(2-methyl-4-pyridinyl)imidazo[1,2-a]pyridin-3-yl]-6-(2-phenylethynyl)-2-pyridinyl]propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(2-methoxy-4-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
(2S)-N-[5-[2-(6-methoxy-3-pyridinyl)-7-methylimidazo[1,2-a]pyridin-3-yl]-6-[2-(1-methyl-2-oxoquinolin-6-yl)ethynyl]-2-pyridinyl]-2-(methylamino)propanamide	IC50	1 nM	US-9481673: 6-alkynyl-pyridine derivatives
2-[(2S)-3-[4-[[4-[[(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]phenyl]methylamino]phenyl]-2-[[(2S)-2-(methylamino)propanoyl]amino]propanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4-dihydro-1H-isoquinoline-3-carboxamide	IC50	1.1 nM	US-9453048: IAP antagonists
(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
(3S)-2-[(2S)-3-[4-[[4-[[(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]phenyl]methoxy]phenyl]-2-[[(2S)-2-(methylamino)propanoyl]amino]propanoyl]-N-(1,2,3,4-tetrahydronaphthalen-1-yl)-3,4-dihydro-1H-isoquinoline-3-carboxamide	IC50	1.11 nM	US-9453048: IAP antagonists
(4S)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-4-[[4-[[4-[[[[(2S)-2-(methylamino)propanoyl]amino]-[(2S)-2-(1,2,3,4-tetrahydronaphthalen-1-ylcarbamoyl)cyclopentanecarbonyl]amino]methyl]phenoxy]methyl]benzoyl]amino]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide	IC50	1.14 nM	US-9453048: IAP antagonists
2-[(2S)-3-[4-[4-[[(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]phenoxy]phenyl]-2-[[(2S)-2-(methylamino)propanoyl]amino]propanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-3,4-dihydro-1H-isoquinoline-3-carboxamide	IC50	1.19 nM	US-9453048: IAP antagonists

ChEMBL bioactivities

2874 potent at pChembl≥5 of 3544 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.77	IC50	0.017	nM	CHEMBL234346
10.22	IC50	0.06	nM	CHEMBL3913296
10.22	IC50	0.06	nM	CHEMBL3918792
10.22	IC50	0.06	nM	CHEMBL3940255
10.22	IC50	0.06	nM	CHEMBL3929256
10.15	IC50	0.07	nM	CHEMBL3930765
10.10	IC50	0.08	nM	CHEMBL3950036
10.10	IC50	0.08	nM	CHEMBL3903824
9.89	IC50	0.13	nM	CHEMBL3976012
9.85	IC50	0.14	nM	CHEMBL3941276
9.85	IC50	0.14	nM	CHEMBL3927714
9.85	IC50	0.14	nM	CHEMBL3950322
9.82	IC50	0.15	nM	CHEMBL3940832
9.80	IC50	0.16	nM	CHEMBL3896723
9.74	IC50	0.18	nM	CHEMBL3917007
9.68	IC50	0.21	nM	CHEMBL3946177
9.66	IC50	0.22	nM	CHEMBL3918274
9.66	IC50	0.22	nM	CHEMBL3918792
9.64	IC50	0.23	nM	CHEMBL3940832
9.60	IC50	0.25	nM	CHEMBL3929256
9.57	IC50	0.27	nM	CHEMBL3954865
9.54	IC50	0.289	nM	CHEMBL3923531
9.52	Kd	0.3	nM	CHEMBL4518501
9.52	IC50	0.3	nM	CHEMBL5916145
9.51	IC50	0.307	nM	CHEMBL3951348
9.49	IC50	0.32	nM	CHEMBL3918981
9.49	IC50	0.325	nM	CHEMBL3929056
9.43	IC50	0.375	nM	CHEMBL3970986
9.40	IC50	0.4	nM	CHEMBL5806178
9.37	IC50	0.429	nM	CHEMBL3945912
9.37	IC50	0.43	nM	CHEMBL1095993
9.35	IC50	0.452	nM	CHEMBL3965515
9.34	IC50	0.46	nM	CHEMBL3950036
9.32	IC50	0.48	nM	CHEMBL3976012
9.31	IC50	0.49	nM	CHEMBL3913296
9.21	IC50	0.62	nM	CHEMBL3929256
9.15	Ki	0.7	nM	CHEMBL2348620
9.14	IC50	0.72	nM	CHEMBL3940255
9.10	IC50	0.801	nM	CHEMBL3897745
9.10	IC50	0.8	nM	CHEMBL5799178
9.10	IC50	0.8	nM	CHEMBL5984721
9.09	IC50	0.815	nM	CHEMBL3956590
9.08	IC50	0.83	nM	CHEMBL4169478
9.06	IC50	0.87	nM	CHEMBL3914612
9.06	IC50	0.8715	nM	CHEMBL3942623
9.05	IC50	0.8995	nM	CHEMBL3900592
9.00	Ki	1	nM	CHEMBL2158606
9.00	IC50	1	nM	CHEMBL3929287
9.00	IC50	1	nM	CHEMBL3929227
9.00	IC50	1	nM	CHEMBL5883598

PubChem BioAssay actives

1229 with measured affinity, of 2244 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
(2S,3S)-2-[[(2S)-1-[(2S)-2-[[(2S)-2-aminopropanoyl]amino]-3-methylbutanoyl]pyrrolidine-2-carbonyl]amino]-3-methylpentanoic acid	1448025: Inhibition of SMAC-derived peptide abuRPFK (5 and 6FAM)-amide interaction with XIAP BIR3 domain (unknown origin) by fluorescence polarization assay	ic50	<0.0001	uM
(2S)-2-(methylamino)-N-[(2S)-3-[6-[(2R,3S)-3-[[(2S)-2-(methylamino)propanoyl]amino]-4-oxo-4-[(2S)-2-[(5-phenylsulfanyltetrazol-1-yl)methyl]pyrrolidin-1-yl]butan-2-yl]oxyhexa-2,4-diynoxy]-1-oxo-1-[(2S)-2-[(5-phenylsulfanyltetrazol-1-yl)methyl]pyrrolidin-1-yl]butan-2-yl]propanamide	1553564: Binding affinity to XIAP-BIR2/BIR3 domain (unknown origin)	kd	0.0003	uM
(2S)-2-(methylamino)-N-[(2S,5S,11S,20S,23S,29S)-29-[[(2S)-2-(methylamino)propanoyl]amino]-4,10,22,28-tetraoxo-2,20-diphenyl-3,9,16,17,18,21,27,34,35,36-decazapentacyclo[32.2.1.116,19.05,9.023,27]octatriaconta-1(37),17,19(38),35-tetraen-11-yl]propanamide	481160: Binding affinity to XIAP linker BIR2-BIR3 domain site 1 by fluorescence polarization assay	ic50	0.0004	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]phenyl]methyl]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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0007	uM
1-[2-[(2R,5R)-2-[[(3R,5R)-3,5-dimethylmorpholin-4-yl]methyl]-5-methylpiperazin-1-yl]acetyl]-6-[(4-fluorophenyl)methyl]-3,3,4-trimethyl-2H-pyrrolo[3,2-b]pyridin-5-one	1362433: Inhibition of full length FLAG-tagged XIAP (unknown origin) interaction with full length untagged caspase-9 expressed in HEK293 cells after 2 hrs by immunoprecipitation assay	ic50	0.0008	uM
(2S)-N-[(3S,9S,12S,18S,24S,27S)-9,24-dibenzyl-18-[[(2S)-2-(methylamino)propanoyl]amino]-2,8,11,17,23,26-hexaoxo-1,7,10,16,22,25-hexazatricyclo[25.3.0.012,16]triacontan-3-yl]-2-(methylamino)propanamide	481160: Binding affinity to XIAP linker BIR2-BIR3 domain site 1 by fluorescence polarization assay	ic50	0.0010	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0010	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0010	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0010	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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0010	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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0010	uM
(5S,8S,10aR)-3-N-[[3-[[[(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]methyl]phenyl]methyl]-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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0010	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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0010	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]butyl]-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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0010	uM
(5S,8S,10aR)-3-N-[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]diazocine-3-carbonyl]amino]octyl]-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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0010	uM
(2S,4R)-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-4-[4-[2-[[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]amino]-3-oxo-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]propyl]phenyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide	1432906: Inhibition of His-tagged XIAP BIR3 (241 to 356 residues) (unknown origin) using fluorescein labeled SMAC peptide as substrate after 60 mins by HTRF assay	ic50	0.0011	uM
(2S)-N-[(2S,5S,11S,20S,23S,29S)-2,20-dibenzyl-29-[[(2S)-2-(methylamino)propanoyl]amino]-4,10,22,28-tetraoxo-3,9,16,17,18,21,27,34,35,36-decazapentacyclo[32.2.1.116,19.05,9.023,27]octatriaconta-1(37),17,19(38),35-tetraen-11-yl]-2-(methylamino)propanamide	481160: Binding affinity to XIAP linker BIR2-BIR3 domain site 1 by fluorescence polarization assay	ic50	0.0013	uM
(5S,8S,10aR)-3-[2-[4-[2-[(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]-2-oxoethyl]phenyl]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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0013	uM
(2S,4R)-4-[4-[2-[[(2R)-3-[2-(1,3-dihydroxypropan-2-ylamino)-2-oxoethyl]sulfanyl-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]amino]-3-oxo-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]propyl]phenyl]-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide	1432906: Inhibition of His-tagged XIAP BIR3 (241 to 356 residues) (unknown origin) using fluorescein labeled SMAC peptide as substrate after 60 mins by HTRF assay	ic50	0.0014	uM
(3S,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	1553564: Binding affinity to XIAP-BIR2/BIR3 domain (unknown origin)	ic50	0.0014	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0015	uM
(5S,8S,10aR)-3-[3-[4-[3-[(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]-3-oxopropyl]phenyl]propanoyl]-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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0015	uM
2-[(2R,5R)-2-[[(3R,5R)-3,5-dimethylmorpholin-4-yl]methyl]-5-methylpiperazin-1-yl]-1-[6-[(4-fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-2H-pyrrolo[3,2-b]pyridin-1-yl]ethanone	1362433: Inhibition of full length FLAG-tagged XIAP (unknown origin) interaction with full length untagged caspase-9 expressed in HEK293 cells after 2 hrs by immunoprecipitation assay	ic50	0.0016	uM
(2S)-N-[(1S)-1-[1-[5-[4-[3-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1H-pyrazol-3-yl)amino]quinazolin-7-yl]oxypropyl]piperazin-1-yl]pyrazine-2-carbonyl]piperidin-4-yl]-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide	1773548: Protac activity at IAP/RIPK2 in human whole blood assessed as inhibition of MDP-induced TNFalpha production by ELISA	ic50	0.0016	uM
(3S,6S,7R,9aS)-7-[[3-[[2-[[3-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-7-yl]methylamino]-3-oxopropyl]amino]-3,4-dioxocyclobuten-1-yl]amino]propanoylamino]methyl]-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;2,2,2-trifluoroacetic acid	716378: Displacement of Smac-1F from human His-tagged XIAP linker BIR2-BIR3 linker (124 to 356 residues) after 3 hrs by fluorescent polarization assay	ic50	0.0016	uM
(2S,4R)-4-[4-[2-[[(2R)-3-[2-[[(2R)-2,3-dihydroxypropyl]-methylamino]-2-oxoethyl]sulfanyl-3-methyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]amino]-3-oxo-3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]propyl]phenyl]-1-[(2S)-3,3-dimethyl-2-[[(2S)-2-(methylamino)propanoyl]amino]butanoyl]-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]pyrrolidine-2-carboxamide	1432906: Inhibition of His-tagged XIAP BIR3 (241 to 356 residues) (unknown origin) using fluorescein labeled SMAC peptide as substrate after 60 mins by HTRF assay	ic50	0.0017	uM
(5S,8S,10aR)-3-N-[3-[[(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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0017	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]cyclohexyl]-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	740370: Binding affinity to XIAP linker BIR2-BIR3 domain (unknown origin) after 3 hrs by competitive fluorescence polarization assay in presence of Smac-1F	ki	0.0017	uM
(2S)-N-[(1S)-1-[1-[2-[4-[3-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1H-pyrazol-3-yl)amino]quinazolin-7-yl]oxypropyl]piperazin-1-yl]pyrimidine-5-carbonyl]piperidin-4-yl]-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide	1773548: Protac activity at IAP/RIPK2 in human whole blood assessed as inhibition of MDP-induced TNFalpha production by ELISA	ic50	0.0020	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells 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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells 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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells 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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0020	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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0020	uM
(5S,8S,10aR)-3-[10-[(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]-10-oxodecanoyl]-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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0020	uM
(5S,8S,10aR)-3-[5-[4-[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-oxopentyl]phenyl]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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0020	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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization 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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0020	uM
(3S,6S,7R,9aS)-7-[[5-[1-[4-[4-[4-[4-[5-[[(3S,6S,7R,9aS)-3-(benzhydrylcarbamoyl)-6-[[(2S)-2-(methylamino)butanoyl]amino]-5-oxo-1,2,3,6,7,8,9,9a-octahydropyrrolo[1,2-a]azepin-7-yl]methylamino]-5-oxopentyl]triazol-1-yl]butyl]phenyl]butyl]triazol-4-yl]pentanoylamino]methyl]-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;2,2,2-trifluoroacetic acid	716378: Displacement of Smac-1F from human His-tagged XIAP linker BIR2-BIR3 linker (124 to 356 residues) after 3 hrs by fluorescent polarization assay	ic50	0.0023	uM
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]-1-[6-[(4-fluorophenyl)methyl]-3,3-dimethyl-2H-pyrrolo[3,2-b]pyridin-1-yl]ethanone	1773548: Protac activity at IAP/RIPK2 in human whole blood assessed as inhibition of MDP-induced TNFalpha production by ELISA	ic50	0.0025	uM
5-[4-[3-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1H-pyrazol-3-yl)amino]quinazolin-7-yl]oxypropyl]piperazin-1-yl]-N-[(3S,5S)-1-[(2R)-3,3-dimethyl-2-[[(2R)-2-(methylamino)propanoyl]amino]butanoyl]-5-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-3-yl]pyrazine-2-carboxamide	1773548: Protac activity at IAP/RIPK2 in human whole blood assessed as inhibition of MDP-induced TNFalpha production by ELISA	ic50	0.0025	uM
1-[6-[(4-fluorophenyl)methyl]-5-(hydroxymethyl)-3,3-dimethyl-2H-pyrrolo[3,2-b]pyridin-1-yl]-2-[(2R,5R)-5-methyl-2-[[(3R)-3-methylmorpholin-4-yl]methyl]piperazin-1-yl]ethanone	1362433: Inhibition of full length FLAG-tagged XIAP (unknown origin) interaction with full length untagged caspase-9 expressed in HEK293 cells after 2 hrs by immunoprecipitation assay	ic50	0.0028	uM
2-[(2R,5R)-2-[[(3R,5R)-3,5-dimethylmorpholin-4-yl]methyl]-5-methylpiperazin-1-yl]-1-[6-[(4-fluorophenyl)methyl]-3,3-dimethyl-2H-pyrrolo[3,2-b]pyridin-1-yl]ethanone	1362433: Inhibition of full length FLAG-tagged XIAP (unknown origin) interaction with full length untagged caspase-9 expressed in HEK293 cells after 2 hrs by immunoprecipitation assay	ic50	0.0029	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0030	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	596633: Binding affinity to human XIAP linker BIR2-BIR3 domain expressed in Escherichia coli BL21(DE3) cells by fluorescence polarization-based assay	ki	0.0030	uM
(5S,8S,10aR)-3-[12-[(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]-12-oxododecanoyl]-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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0030	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	694868: Binding affinity to BIR2-BIR3 domain of XIAP by fluorescence polarization assay	ki	0.0030	uM
(5R)-1-[(2S)-3-[4-[3-[[(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]amino]-3-oxoprop-1-ynyl]phenyl]-2-[[(2S)-2-(methylamino)propanoyl]amino]propanoyl]-3,3-dimethyl-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,3-azasilolidine-5-carboxamide	1393303: Inhibition of N-terminal His-tagged XIAP BIR3 domain (241 to 356 residues) (unknown origin) using fluorescein labeled SMAC peptide as substrate after 60 mins by TR-FRET assay	ic50	0.0030	uM
(2S)-N-[(1S)-1-[1-[2-[4-[3-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1H-pyrazol-3-yl)amino]quinazolin-7-yl]oxypropyl]piperidin-1-yl]pyrimidine-5-carbonyl]piperidin-4-yl]-2-[(2S)-2-[4-(4-fluorobenzoyl)-1,3-thiazol-2-yl]pyrrolidin-1-yl]-2-oxoethyl]-2-(methylamino)propanamide	1773548: Protac activity at IAP/RIPK2 in human whole blood assessed as inhibition of MDP-induced TNFalpha production by ELISA	ic50	0.0032	uM
(5S,8S,10aR)-3-[5-[4-[3-[6-tert-butylsulfonyl-4-[(4,5-dimethyl-1H-pyrazol-3-yl)amino]quinazolin-7-yl]oxypropyl]piperazin-1-yl]pyrazine-2-carbonyl]-5-[[(2S)-2-(methylamino)propanoyl]amino]-6-oxo-N-[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]-1,2,4,5,8,9,10,10a-octahydropyrrolo[1,2-a][1,5]diazocine-8-carboxamide	1773548: Protac activity at IAP/RIPK2 in human whole blood assessed as inhibition of MDP-induced TNFalpha production by ELISA	ic50	0.0032	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	affects expression, affects cotreatment, decreases expression, increases reaction	19
Cisplatin	increases activity, increases expression, increases cleavage, increases reaction, decreases response to substance (+5 more)	13
Curcumin	increases expression, affects cotreatment, decreases expression, increases reaction, affects expression (+1 more)	13
Bortezomib	decreases expression, decreases reaction, affects expression, increases reaction, affects cotreatment (+3 more)	10
Doxorubicin	affects localization, increases expression, decreases response to substance, affects response to substance, affects cotreatment (+2 more)	9
Resveratrol	decreases reaction, increases expression, affects cotreatment, decreases expression	8
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	affects binding, decreases reaction, increases reaction, increases degradation, decreases expression (+3 more)	6
alvocidib	decreases expression, increases reaction, affects cotreatment, increases cleavage	6
Vorinostat	increases expression, decreases response to substance, affects cotreatment, decreases expression, decreases reaction (+2 more)	6
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases reaction, increases expression, decreases response to substance, affects cotreatment, decreases expression	5
Fluorouracil	affects cotreatment, decreases response to substance, increases expression, decreases expression, increases reaction (+3 more)	5
Nicotine	affects cotreatment, decreases reaction, increases expression, affects reaction	5
Paclitaxel	affects expression, decreases expression, decreases reaction, increases expression, decreases response to substance	5
sodium arsenite	decreases reaction, increases expression, increases ubiquitination, decreases expression, increases abundance (+4 more)	4
diallyl trisulfide	increases degradation, decreases response to substance, decreases expression, decreases reaction	4
Acetylcysteine	affects cotreatment, decreases expression, decreases reaction, increases cleavage	4
Valproic Acid	affects cotreatment, decreases expression, affects expression	4
mangiferin	decreases reaction, increases expression, decreases expression	3
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects cotreatment, decreases expression, decreases reaction, increases expression	3
Docetaxel	decreases expression, decreases response to substance	3
Sorafenib	affects cotreatment, increases cleavage, decreases expression	3
Roscovitine	affects cotreatment, decreases expression	3
Butyrates	affects cotreatment, decreases expression, decreases reaction, increases abundance	3
Cadmium	affects cotreatment, increases abundance, increases expression, decreases expression, decreases reaction	3
Camptothecin	affects cotreatment, decreases expression, decreases response to substance	3
Dexamethasone	decreases expression, decreases reaction, increases expression	3
Hydrogen Peroxide	affects expression, decreases expression, affects cotreatment, increases expression, increases reaction	3
Plant Extracts	increases expression, decreases expression, affects cotreatment	3
Quercetin	decreases expression, increases reaction	3
Reactive Oxygen Species	affects cotreatment, decreases expression, increases abundance, increases chemical synthesis	3

ChEMBL screening assays

499 unique, capped per target: 468 binding, 24 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1010647	Binding	Binding affinity to XIAP-BIR3 domain by fluorescence polarization competitive assay	Orally bioavailable antagonists of inhibitor of apoptosis proteins based on an azabicyclooctane scaffold. — J Med Chem
CHEMBL1106519	Functional	Antagonist activity at XIAP BIR3 domain assessed as restoration of caspase 9 activity by caspase-Glo 9 assay	Cyclopeptide Smac mimetics as antagonists of IAP proteins. — Bioorg Med Chem Lett
CHEMBL4769840	ADMET	Protac activity at BCL-XL/XIAP E3 ligase in human platelets assessed as degradation of BCL-XL at 0.04 uM measured after 16 hrs by western blot analysis	Discovery of IAP-recruiting BCL-X PROTACs as potent degraders across multiple cancer cell lines. — Eur J Med Chem

Cellosaurus cell lines

11 cell lines: 8 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8RV	Abcam HCT 116 XIAP KO	Cancer cell line	Male
CVCL_B9UD	Abcam A-549 XIAP KO	Cancer cell line	Male
CVCL_D8DF	Ubigene A-549 XIAP KO	Cancer cell line	Male
CVCL_D8YA	Ubigene HCT 116 XIAP KO	Cancer cell line	Male
CVCL_D9VW	Ubigene HEK293 XIAP KO	Transformed cell line	Female
CVCL_E0T6	Ubigene HeLa XIAP KO	Cancer cell line	Female
CVCL_E2PC	HAP1 XIAP (-) 1	Cancer cell line	Male
CVCL_E2PD	HAP1 XIAP (-) 2	Cancer cell line	Male
CVCL_KU23	HeLa SilenciX XIAP	Cancer cell line	Female
CVCL_UW12	CHO-K1-XIAP	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03113760	PHASE3	COMPLETED	Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency
NCT03512314	PHASE3	COMPLETED	Therapeutic Use of Tadekinig Alfa in NLRC4 Mutation and XIAP Deficiency As Open Label Extension
NCT06309823	PHASE3	COMPLETED	A Single-patient Clinical Trial of MAS825 in a Patient With XIAP Deficiency
NCT00442182	PHASE2	UNKNOWN	The Efficacy and Safety of ITF2357 in AIS
NCT07433621	PHASE1	RECRUITING	Quercetin in Patients With XIAP (X-linked Inhibitor of Apoptosis) Deficiency
NCT00887939	Not specified	COMPLETED	Pathogenesis of Physical Induced Urticarial Syndromes
NCT03510442	Not specified	RECRUITING	Natural History, Genetics, and Pathophysiology of Systemic Juvenile Idiopathic Arthritis, Adult-Onset Still’s Disease, and Related Conditions
NCT06248957	Not specified	RECRUITING	SYSTEMS-LEVEL ANALYSES OF IMMUNE DYSREGULATION