CXCL8

Summary

CXCL8 (C-X-C motif chemokine ligand 8, HGNC:6025) is a protein-coding gene on chromosome 4q13.3, encoding Interleukin-8 (P10145). Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection.

The protein encoded by this gene is a member of the CXC chemokine family and is a major mediator of the inflammatory response. The encoded protein is commonly referred to as interleukin-8 (IL-8). IL-8 is secreted by mononuclear macrophages, neutrophils, eosinophils, T lymphocytes, epithelial cells, and fibroblasts. It functions as a chemotactic factor by guiding the neutrophils to the site of infection. Bacterial and viral products rapidly induce IL-8 expression. IL-8 also participates with other cytokines in the proinflammatory signaling cascade and plays a role in systemic inflammatory response syndrome (SIRS). This gene is believed to play a role in the pathogenesis of the lower respiratory tract infection bronchiolitis, a common respiratory tract disease caused by the respiratory syncytial virus (RSV). The overproduction of this proinflammatory protein is thought to cause the lung inflammation associated with csytic fibrosis. This proinflammatory protein is also suspected of playing a role in coronary artery disease and endothelial dysfunction. This protein is also secreted by tumor cells and promotes tumor migration, invasion, angiogenesis and metastasis. This chemokine is also a potent angiogenic factor. The binding of IL-8 to one of its receptors (IL-8RB/CXCR2) increases the permeability of blood vessels and increasing levels of IL-8 are positively correlated with increased severity of multiple disease outcomes (eg, sepsis). This gene and other members of the CXC chemokine gene family form a gene cluster in a region of chromosome 4q.

Source: NCBI Gene 3576 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 14 total
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000584

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6025
Approved symbol	CXCL8
Name	C-X-C motif chemokine ligand 8
Location	4q13.3
Locus type	gene with protein product
Status	Approved
Aliases	SCYB8, LUCT, LECT, MDNCF, TSG-1, IL-8, NAP-1, 3-10C, MONAP, AMCF-I, LYNAP, NAF, b-ENAP, GCP-1, K60, GCP1, NAP1
Ensembl gene	ENSG00000169429
Ensembl biotype	protein_coding
OMIM	146930
Entrez	3576

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 2 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000307407, ENST00000401931, ENST00000483500, ENST00000696131, ENST00000696132

RefSeq mRNA: 2 — MANE Select: NM_000584 NM_000584, NM_001354840

CCDS: CCDS34005, CCDS87231

Canonical transcript exons

ENST00000307407 — 4 exons

Exon	Start	End
ENSE00003966099	73740569	73740722
ENSE00003966100	73742449	73743716
ENSE00003966101	73741542	73741677
ENSE00003966102	73741949	73742032

Expression profiles

Bgee: expression breadth ubiquitous, 252 present calls, max score 99.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1068.1382 / max 199416.1403, expressed in 1285 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
48182	1054.7012	1283
48196	3.7498	380
48195	1.7564	303
48203	1.2533	240
48202	1.2223	257
48189	0.8516	221
48191	0.7794	216
48193	0.6717	188
48197	0.5979	184
48192	0.5133	168

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
periodontal ligament	UBERON:0008266	99.91	gold quality
granulocyte	CL:0000094	98.95	gold quality
type B pancreatic cell	CL:0000169	98.70	gold quality
islet of Langerhans	UBERON:0000006	98.50	gold quality
cartilage tissue	UBERON:0002418	96.75	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.74	gold quality
monocyte	CL:0000576	96.67	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.22	gold quality
leukocyte	CL:0000738	96.14	gold quality
bone marrow cell	CL:0002092	95.96	gold quality
mononuclear cell	CL:0000842	95.89	gold quality
sperm	CL:0000019	95.72	gold quality
gall bladder	UBERON:0002110	94.72	gold quality
epithelial cell of pancreas	CL:0000083	94.47	gold quality
mucosa of urinary bladder	UBERON:0001259	93.81	gold quality
nasal cavity epithelium	UBERON:0005384	92.93	gold quality
bronchus	UBERON:0002185	92.68	gold quality
epithelium of bronchus	UBERON:0002031	92.61	gold quality
bronchial epithelial cell	CL:0002328	92.05	gold quality
trachea	UBERON:0003126	91.80	gold quality
male germ cell	CL:0000015	91.75	gold quality
vena cava	UBERON:0004087	90.64	gold quality
bone marrow	UBERON:0002371	90.34	gold quality
nasal cavity mucosa	UBERON:0001826	89.99	gold quality
palpebral conjunctiva	UBERON:0001812	89.93	gold quality
endothelial cell	CL:0000115	89.44	gold quality
stromal cell of endometrium	CL:0002255	89.16	gold quality
parietal pleura	UBERON:0002400	89.09	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.85	silver quality
vermiform appendix	UBERON:0001154	87.32	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-GEOD-139324	yes	90538.21
E-HCAD-29	yes	72617.32
E-HCAD-36	yes	34028.69
E-MTAB-6678	yes	22736.51
E-MTAB-8142	yes	21726.70
E-MTAB-7052	yes	19478.41
E-MTAB-9221	yes	14020.35
E-HCAD-24	yes	11710.70
E-HCAD-10	yes	10182.98
E-MTAB-6075	yes	6707.01
E-CURD-95	yes	5462.56
E-MTAB-8884	yes	5064.45
E-MTAB-9067	yes	4152.73
E-GEOD-76312	yes	3000.87
E-MTAB-8559	yes	1992.39

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, AIRE, AP1, APEX1, AR, ATF3, ATF4, BACH1, BCL3, BHLHE40, CEBPA, CEBPB, CEBPD, CEBPG, CNOT7, CREB1, CRP, CTNNB1, DDIT3, DEK, DNMT3A, EGR1, ELF4, EP300, EPAS1, ERG, ESR1, ESR2, ETS1, ETS2, ETV4, F3, FOS, FOSB, FOSL1, FOXC1, FOXO1, FOXO3, GDF2, GTF3A

miRNA regulators (miRDB)

67 targeting CXCL8, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10523-5P	99.91	69.22	2038
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4420	99.82	70.08	1624
HSA-MIR-181B-2-3P	99.81	70.06	1646
HSA-MIR-181B-3P	99.81	70.06	1646
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-587	99.64	70.86	2611

Literature-anchored findings (GeneRIF, showing 40)

• This lithium-induced up-regulation of NF-kappa B and MAP kinase activation was associated with an enhancement of interleukin-8 mRNA accumulation as well as an increase in interleukin-8 protein release. (PMID:11756416)
• Vascular endothelial growth factor modulates neutrophil transendothelial migration via up-regulation of interleukin-8 in human brain microvascular endothelial cells (PMID:11784713)
• Conformational changes of dimeric IL-8 induced by heparan sulfate, but not by heparin, refer to an “activation” of the chemokine which is hypothesized to be important for the migration of neutrophils to inflammatory sites. (PMID:11814358)
• IFN-gamma primed CD14(high) human gingival fibroblasts to enhance production of IL-8 in response to LPS through augmentation of the CD14-TLR system (PMID:11854210)
• Increased plasma levels of interleukin-6 and interleukin-8 are observed in beta-thalassaemia major patients and may be relevant in the pathophysiology of beta-thalassaemia (PMID:11855786)
• Human bronchial epithelium releases neutrophil chemotactic factor. (PMID:11868823)
• Lidocaine inhibits secretion of IL-8 and IL-1beta and stimulates secretion of IL-1 receptor antagonist by epithelial cells. Lidocaine inhibits the expression of il-8 mRNA. (PMID:11876744)
• secretion induced by combined effects of protein kinase C and ERK activation with TFF-papetide and TNF-alpha (PMID:11884401)
• TNF-alpha induction of IL-8 in vascular endothelium is down-regulated in vitro via an eotaxin/CCL11-induced acceleration of IL-8 mRNA decay. (PMID:11884459)
• Cushing’s syndrome patients have markedly elevated levels of the proinflammatory cytokine IL-8 (PMID:11888846)
• The effect of LPS on neutrophils from patients with high risk of type 1 diabetes mellitus in relation to IL-8, IL-10 and IL-12 production and apoptosis in vitro. (PMID:11896938)
• mechanical strain increased interleukin-8 protein expression (PMID:11910304)
• Mycobacterium bovis-mediated upregulation of IL-8 biosynthesis and release by human monocytes involves intracellular protein kinase signaling pathways and transcription factor NF-kappa B. (PMID:11911801)
• process of cervical dilatation during parturition at term is associated with an increased expression of interleukin-1 beta, interleukin-6 and interleukin-8 mRNA in the lower uterine segment (PMID:11950481)
• Expression of IL8 in primary gastrointestinal non-Hodgkin’s lymphoma. (PMID:11956621)
• Secretion levels of sIL-2R, IL-6, IL-8, IL-10, and TNF-alpha, but not IL-4 and IL-12, are elevated in activated T-cells in large granular lymphocytic leukemia associated with autoimmune disorders. (PMID:11960393)
• IL-8 is down regulated in ovarian carcinoma and in serous effusions (PMID:11964077)
• determine the cellular contents and concentrations of interleukin 6 (IL-6), interleukin 8 (IL-8) and tumour necrosis factor alpha (TNF-alpha) in fluids of patients with spermatocele or epididymal cyst (PMID:11966578)
• TF-FVIIa signaling induced increased transcription as well as mRNA stabilization leading to the significant up-regulation of IL-8 protein synthesis (PMID:11973337)
• Inflammatory cytokines mediate C-C (monocyte chemotactic protein 1) and C-X-C (interleukin 8) chemokine expression in human pleural fibroblasts. (PMID:11989790)
• REVIEW: Role of IL8 in leukocytosis and stem cell mobilization. (PMID:11999552)
• IL8 is overexpressed in paclitaxel-resistant human osteosarcoma cells (PMID:12027404)
• Huh7 cells expressing the hepatitis C viral protein NS5A showed an up-regulation of interleukin-8 (PMID:12033786)
• expression in airway epithelial cells by interleukin-17 (PMID:12034575)
• regulation of secretion in bronchial epithelial cells by phospholipase D activation by sphingosine 1-phosphate (PMID:12039947)
• Weight loss in obese subjects was associated with opposite changes in the secretion and transcription of IL-8 and TNF-alpha in the adipose tissue, as well as in plasma (PMID:12055326)
• IL-8 production by RET tyrosine kinase is regulated by multiple signaling pathways (PMID:12056817)
• Endogenous expression in nasopharyngeal carcinoma cells (PMID:12060853)
• TNFalpha and IL-8 regulate the expression and function of CD44 variant proteins in human colon carcinoma cells. (PMID:12090473)
• Native LDL potentiate TNF alpha and IL-8 production by human mononuclear cells. (PMID:12091490)
• Mycobacterium bovis-mediated upregulation of IL8 in human monocyes is down-regulated by IL10. (PMID:12093676)
• Glutamine decreases production of this and il6 but not nitric oxide and prostaglandins e(2) production by human gut in-vitro. (PMID:12096924)
• Endotoxin-stimulated production is increased in short-term cultures of whole blood from healthy term neonates. (PMID:12096927)
• Anti-CD45 isoform antibodies enhance phagocytosis and gene expression of IL-8 and TNF-alpha in human neutrophils by differential suppression on protein tyrosine phosphorylation and p56lck tyrosine kinase. (PMID:12100025)
• plays a role in the pathogenesis of the otitis media with effusion (review) (PMID:12101072)
• new autocrine function of secreted interleukin-8 and the intracellular signal transduction leading to the regulation of cytosolic calcium and to a migratory tumor cell phenotype (PMID:12115500)
• Simvastatin reduces expression of the proinflammatory cytokine interleukin-8 in circulating monocytes from hypercholesterolemic patients. (PMID:12117737)
• Leishmania promastigotes release a granulocyte chemotactic factor and induce interleukin-8 release by neutrophil granulocytes (PMID:12117926)
• Induction of IL-8 in THP-1 macrophages and human microvascular endothelial cells during Bartonella henselae infection (PMID:12117969)
• interleukin-8 secretion from Mycobacterium tuberculosis-infected monocytes is regulated by protein tyrosine kinases (PMID:12117995)

Cross-species orthologs

0 orthologs

Paralogs (12): CXCL2 (ENSG00000081041), PF4V1 (ENSG00000109272), CXCL6 (ENSG00000124875), CXCL9 (ENSG00000138755), CXCL13 (ENSG00000156234), CXCL3 (ENSG00000163734), CXCL5 (ENSG00000163735), PPBP (ENSG00000163736), PF4 (ENSG00000163737), CXCL1 (ENSG00000163739), CXCL10 (ENSG00000169245), CXCL11 (ENSG00000169248)

Protein

Protein identifiers

Interleukin-8 — P10145 (reviewed: P10145)

Alternative names: C-X-C motif chemokine 8, Chemokine (C-X-C motif) ligand 8, Emoctakin, Granulocyte chemotactic protein 1, Monocyte-derived neutrophil chemotactic factor, Monocyte-derived neutrophil-activating peptide, Neutrophil-activating protein 1, Protein 3-10C, T-cell chemotactic factor

All UniProt accessions (3): A0A8Q3SIG6, C9J4T6, P10145

UniProt curated annotations — full annotation on UniProt →

Function. Chemotactic factor that mediates inflammatory response by attracting neutrophils, basophils, and T-cells to clear pathogens and protect the host from infection. Also plays an important role in neutrophil activation. Released in response to an inflammatory stimulus, exerts its effect by binding to the G-protein-coupled receptors CXCR1 and CXCR2, primarily found in neutrophils, monocytes and endothelial cells. G-protein heterotrimer (alpha, beta, gamma subunits) constitutively binds to CXCR1/CXCR2 receptor and activation by IL8 leads to beta and gamma subunits release from Galpha (GNAI2 in neutrophils) and activation of several downstream signaling pathways including PI3K and MAPK pathways.

Subunit / interactions. Homodimer. Dimer formation is disrupted by tick evasin-3. Interacts with TNFAIP6 (via Link domain); this interaction interferes with chemokine binding to glycosaminoglycans.

Subcellular location. Secreted.

Post-translational modifications. Several N-terminal processed forms are produced by proteolytic cleavage after secretion from at least peripheral blood monocytes, leukcocytes and endothelial cells. In general, IL-8(1-77) is referred to as interleukin-8. IL-8(6-77) is the most promiment form. Citrullination at Arg-27 prevents proteolysis, and dampens tissue inflammation, it also enhances leukocytosis, possibly through impaired chemokine clearance from the blood circulation. (Microbial infection) Cleaved by group A Streptococcus protease SpyCEP; leading to impaired neutrophil endothelial transmigration and thus increased virulence.

Induction. By ER stress in a DDIT3/CHOP-dependent manner.

Similarity. Belongs to the intercrine alpha (chemokine CxC) family.

RefSeq proteins (2): NP_000575, NP_001341769 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001089	Chemokine_CXC	Family
IPR001811	Chemokine_IL8-like_dom	Domain
IPR018048	Chemokine_CXC_CS	Conserved_site
IPR033899	CXC_Chemokine_domain	Domain
IPR036048	Interleukin_8-like_sf	Homologous_superfamily
IPR039809	Chemokine_b/g/d	Family

Pfam: PF00048

UniProt features (27 total): chain 7, strand 7, mutagenesis site 3, disulfide bond 2, helix 2, site 2, signal peptide 1, modified residue 1, sequence conflict 1, turn 1

Structure

Experimental structures (PDB)

22 structures.

PDB	Method	Resolution (Å)
4XDX	X-RAY DIFFRACTION	0.95
5D14	X-RAY DIFFRACTION	1
6N2U	X-RAY DIFFRACTION	1.25
3IL8	X-RAY DIFFRACTION	2
1ICW	X-RAY DIFFRACTION	2.01
6WZM	X-RAY DIFFRACTION	2.28
1QE6	X-RAY DIFFRACTION	2.35
8XX6	ELECTRON MICROSCOPY	2.99
8XWN	ELECTRON MICROSCOPY	3.29
6LFO	ELECTRON MICROSCOPY	3.4
8IC0	ELECTRON MICROSCOPY	3.41
6LFM	ELECTRON MICROSCOPY	3.5
8YNF	ELECTRON MICROSCOPY	3.65
1IKL	SOLUTION NMR
1IKM	SOLUTION NMR
1IL8	SOLUTION NMR
1ILP	SOLUTION NMR
1ILQ	SOLUTION NMR
1ROD	SOLUTION NMR
2IL8	SOLUTION NMR
5WDZ	SOLUTION NMR
6XMN	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10145-F1	88.76	0.67

Antibody-complex structures (SAbDab): 5 — 6LFM, 6LFO, 6WZM, 8IC0, 8XX6

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 (2): 27–28 (cleavage; by thrombin); 28–29 (cleavage; by mmp9)

Post-translational modifications (1): 27

Disulfide bonds (2): 34–61, 36–77

Mutagenesis-validated functional residues (3):

Position	Phenotype
91	decreases heparin-binding activity. impairs heparin-binding activity and leukocyte transendothelial migration; when asso
94	impairs heparin-binding activity and leukocyte transendothelial migration; when associated with a-91 and a-95.
95	impairs heparin-binding activity and leukocyte transendothelial migration; when associated with a-91 and a-94.

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-418594	G alpha (i) signalling events
R-HSA-6783783	Interleukin-10 signaling
R-HSA-6785807	Interleukin-4 and Interleukin-13 signaling

MSigDB gene sets: 645 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_UP, GSE18804_SPLEEN_MACROPHAGE_VS_TUMORAL_MACROPHAGE_UP, MODULE_52, MODULE_92, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, MODULE_516, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_LEUKOCYTE_MIGRATION, HARRIS_HYPOXIA, GOBP_CELL_CHEMOTAXIS

GO Biological Process (32): angiogenesis (GO:0001525), response to molecule of bacterial origin (GO:0002237), chemotaxis (GO:0006935), inflammatory response (GO:0006954), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), negative regulation of cell population proliferation (GO:0008285), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), calcium-mediated signaling (GO:0019722), regulation of cell adhesion (GO:0030155), neutrophil chemotaxis (GO:0030593), receptor internalization (GO:0031623), response to endoplasmic reticulum stress (GO:0034976), intracellular signal transduction (GO:0035556), neutrophil activation (GO:0042119), cellular response to fibroblast growth factor stimulus (GO:0044344), regulation of single stranded viral RNA replication via double stranded DNA intermediate (GO:0045091), negative regulation of G protein-coupled receptor signaling pathway (GO:0045744), positive regulation of angiogenesis (GO:0045766), embryonic digestive tract development (GO:0048566), induction of positive chemotaxis (GO:0050930), negative regulation of cell adhesion molecule production (GO:0060354), antimicrobial humoral immune response mediated by antimicrobial peptide (GO:0061844), cellular response to lipopolysaccharide (GO:0071222), cellular response to interleukin-1 (GO:0071347), cellular response to tumor necrosis factor (GO:0071356), positive regulation of neutrophil chemotaxis (GO:0090023), regulation of entry of bacterium into host cell (GO:2000535), defense response (GO:0006952), immune response (GO:0006955), cell chemotaxis (GO:0060326)

GO Molecular Function (6): interleukin-8 receptor binding (GO:0005153), chemokine activity (GO:0008009), heparin binding (GO:0008201), CXCR chemokine receptor binding (GO:0045236), cytokine activity (GO:0005125), protein binding (GO:0005515)

GO Cellular Component (3): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by Interleukins	2
Cellular Senescence	1
Class A/1 (Rhodopsin-like receptors)	1
Peptide ligand-binding receptors	1
PERK regulates gene expression	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	2
signal transduction	2
gene expression	2
regulation of gene expression	2
chemokine receptor binding	2
cellular anatomical structure	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
response to bacterium	1
response to external biotic stimulus	1
response to chemical	1
taxis	1
defense response	1
cell communication	1
cellular process	1
signaling	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
intracellular signaling cassette	1
cell adhesion	1
granulocyte chemotaxis	1
neutrophil migration	1
receptor-mediated endocytosis	1
cellular response to stress	1
intracellular anatomical structure	1
granulocyte activation	1
cellular response to growth factor stimulus	1
response to fibroblast growth factor	1
single stranded viral RNA replication via double stranded DNA intermediate	1
regulation of viral genome replication	1
regulation of RNA biosynthetic process	1
G protein-coupled receptor signaling pathway	1
regulation of G protein-coupled receptor signaling pathway	1
negative regulation of signal transduction	1
angiogenesis	1

Protein interactions and networks

STRING

5340 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCL8	CXCR2	P25025	999
CXCL8	CXCR1	P25024	998
CXCL8	IL4	P05112	996
CXCL8	CCR2	P41597	995
CXCL8	CXCR3	P49682	994
CXCL8	CCR1	P32246	993
CXCL8	CXCR4	P30991	991
CXCL8	ACKR1	Q16570	990
CXCL8	IL2	P01585	985
CXCL8	IL6	P05231	977
CXCL8	CCL4	P13236	970
CXCL8	TNF	P01375	965
CXCL8	IL1B	P01584	963
CXCL8	CCR3	P51677	963
CXCL8	VWF	P04275	962

IntAct

38 interactions, top by confidence:

A	B	Type	Score
	CXCL8	psi-mi:“MI:0407”(direct interaction)	0.610
CXCR2	CXCL8	psi-mi:“MI:0407”(direct interaction)	0.610
CXCR2	CXCL8	psi-mi:“MI:0915”(physical association)	0.610
CXCL8	CXCR2	psi-mi:“MI:0915”(physical association)	0.610
CXCL8	ahcY	psi-mi:“MI:0914”(association)	0.600
CXCL8	atsG	psi-mi:“MI:0407”(direct interaction)	0.600
CXCL8	ahcY	psi-mi:“MI:0407”(direct interaction)	0.600
CXCL8	glmU	psi-mi:“MI:0407”(direct interaction)	0.600
TNFAIP6	CXCL8	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL8	TNFAIP6	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL8	PF4	psi-mi:“MI:0407”(direct interaction)	0.560
PF4	CXCL8	psi-mi:“MI:0407”(direct interaction)	0.560
CXCL8	CCL8	psi-mi:“MI:0407”(direct interaction)	0.440
CCL2	CXCL8	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (28): CXCL8 (Synthetic Growth Defect), CXCL8 (Co-crystal Structure), FANCI (Reconstituted Complex), CXCL8 (Reconstituted Complex), SDC1 (Reconstituted Complex), CXCL8 (Reconstituted Complex), CXCL8 (Reconstituted Complex), CXCL8 (Reconstituted Complex), CXCL8 (Reconstituted Complex), CXCL8 (Reconstituted Complex), CCL8 (Reconstituted Complex), CXCL8 (Reconstituted Complex), CXCL8 (Affinity Capture-RNA), CXCL8 (Affinity Capture-RNA), ZNF598 (Protein-RNA)

ESM2 similar proteins: A0A0R4INB9, A9QWP9, B0R191, K7XWG4, O43927, O55038, O62812, P02776, P02778, P06765, P10145, P10146, P10720, P17515, P18340, P19874, P22362, P26894, P36925, P41324, P43030, P46653, P48298, P48973, P49113, P67813, P67814, P78556, P79255, P80325, P82943, P97545, P97884, P97885, Q03366, Q07325, Q09141, Q102R3, Q2KIQ8, Q5KSV9

Diamond homologs: A0A0R4INB9, A9QWP9, B0R191, O46675, O46676, O46677, O46678, O55235, O62812, P02775, P02776, P02778, P06765, P08317, P09340, P09341, P10145, P10720, P10889, P12850, P14095, P17515, P18340, P19874, P19875, P19876, P22952, P26894, P30034, P30348, P30782, P36925, P41324, P42830, P43030, P46653, P47854, P48973, P49113, P50228

SIGNOR signaling

13 interactions.

A	Effect	B	Mechanism
CXCL8	up-regulates	CXCR1	binding
CXCL8	up-regulates	CXCR2	binding
ELF4	“up-regulates quantity by expression”	CXCL8	“transcriptional regulation”
CRP	“up-regulates quantity by expression”	CXCL8	“transcriptional regulation”
ERG	“down-regulates quantity by repression”	CXCL8	“transcriptional regulation”
CXCL8	up-regulates	Inflammation
S	“up-regulates quantity”	CXCL8
NfKb-p65/p50	“up-regulates quantity by expression”	CXCL8	“transcriptional regulation”
AP1	“up-regulates quantity by expression”	CXCL8	“transcriptional regulation”
CXCL8	up-regulates	ARDS
hsa-miR-23a-5p	“down-regulates quantity by repression”	CXCL8	“post transcriptional regulation”
hsa-miR-520a-5p	“down-regulates quantity by repression”	CXCL8	“post transcriptional regulation”
CXCL8	up-regulates	Angiogenesis

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 15 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.

GO biological processes:

GO term	Partners	Fold	FDR
inflammatory response	5	15.7×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	3
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

146 predictions. Top by Δscore:

Variant	Effect	Δscore
4:73740719:GAAG:G	donor_gain	1.0000
4:73740720:AAGGT:A	donor_loss	1.0000
4:73740723:G:GG	donor_gain	1.0000
4:73740723:GTAA:G	donor_loss	1.0000
4:73741537:A:AG	acceptor_gain	1.0000
4:73741539:CAG:C	acceptor_loss	1.0000
4:73741540:A:AG	acceptor_gain	1.0000
4:73741540:A:AT	acceptor_loss	1.0000
4:73741541:G:GC	acceptor_gain	1.0000
4:73741541:GGT:G	acceptor_gain	1.0000
4:73741673:ATTAT:A	donor_gain	1.0000
4:73741674:TTAT:T	donor_gain	1.0000
4:73741675:TAT:T	donor_gain	1.0000
4:73741675:TATGT:T	donor_loss	1.0000
4:73741676:AT:A	donor_gain	1.0000
4:73741676:ATGTA:A	donor_loss	1.0000
4:73741677:TG:T	donor_loss	1.0000
4:73741678:G:GA	donor_loss	1.0000
4:73741678:G:GG	donor_gain	1.0000
4:73741679:TAAG:T	donor_loss	1.0000
4:73741942:A:AG	acceptor_gain	1.0000
4:73741943:T:G	acceptor_gain	1.0000
4:73741944:TTCA:T	acceptor_gain	1.0000
4:73741945:TCA:T	acceptor_gain	1.0000
4:73741946:CAGT:C	acceptor_gain	1.0000
4:73741946:CAGTG:C	acceptor_loss	1.0000
4:73741947:A:AC	acceptor_loss	1.0000
4:73741947:A:AG	acceptor_gain	1.0000
4:73741947:AG:A	acceptor_gain	1.0000
4:73741947:AGT:A	acceptor_gain	1.0000

AlphaMissense

641 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:73742000:G:C	W84C	0.996
4:73742000:G:T	W84C	0.996
4:73741977:T:A	C77S	0.988
4:73741978:G:C	C77S	0.988
4:73741658:T:A	C61S	0.987
4:73741659:G:C	C61S	0.987
4:73741998:T:A	W84R	0.986
4:73741998:T:C	W84R	0.986
4:73741583:T:A	C36S	0.985
4:73741584:G:C	C36S	0.985
4:73741977:T:C	C77R	0.985
4:73741577:T:A	C34S	0.983
4:73741578:G:C	C34S	0.983
4:73741979:T:G	C77W	0.981
4:73741659:G:A	C61Y	0.980
4:73741577:T:C	C34R	0.979
4:73741658:T:C	C61R	0.979
4:73741660:C:G	C61W	0.979
4:73741583:T:C	C36R	0.978
4:73741951:T:A	V68E	0.976
4:73741674:T:C	I66T	0.973
4:73741674:T:G	I66S	0.973
4:73741978:G:A	C77Y	0.971
4:73741659:G:T	C61F	0.969
4:73741623:T:A	I49N	0.964
4:73741981:T:C	L78P	0.963
4:73741632:T:C	L52P	0.962
4:73741650:G:A	G58E	0.961
4:73741578:G:A	C34Y	0.960
4:73741584:G:A	C36Y	0.960

dbSNP variants (sampled 300 via entrez): RS1000003014 (4:73739370 A>T), RS1000022557 (4:73743126 T>A), RS1000275946 (4:73739885 A>G), RS1000557302 (4:73740928 A>T), RS1000965738 (4:73740637 A>G), RS1001372497 (4:73740302 A>G,T), RS1001445887 (4:73739737 T>C), RS1002355480 (4:73740544 A>G), RS1002446795 (4:73741301 T>C,G), RS1003403403 (4:73739459 A>G), RS1003486585 (4:73742627 T>C), RS1004562097 (4:73739792 T>A), RS1004621228 (4:73739059 A>C), RS1004929799 (4:73740334 T>C), RS1005457503 (4:73742321 C>G,T)

Disease associations

OMIM: gene MIM:146930 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): cholangiocarcinoma (MONDO:0019087)

Orphanet (1): Cholangiocarcinoma (Orphanet:70567)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001725_78	Inflammatory bowel disease	3.000000e-08
GCST009879_4	Coronary artery disease	3.000000e-29
GCST010476_2	Myocardial infarction	1.000000e-25
GCST010477_9	Hypertension	7.000000e-07
GCST010478_6	Chronic kidney disease	8.000000e-08
GCST010836_3	Ischemic stroke	6.000000e-09

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018281	Cholangiocarcinoma	C04.557.470.200.025.450

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2157 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 386,113 (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
CHEMBL1020	TOLMETIN	4	60,332
CHEMBL139	DICLOFENAC	4	125,009
CHEMBL295124	BERBERINE	4	26,682
CHEMBL6	INDOMETHACIN	4	156,366
CHEMBL427526	(R)-IBUPROPHEN	1	17,724

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

PharmGKB clinical annotations

2 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs1126647	Toxicity	3	sunitinib	Renal Cell Carcinoma
rs4073	Efficacy	3	bevacizumab	Macular Degeneration

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs4073	CXCL8	3	1.75	1	bevacizumab
rs1126647	CXCL8	3	1.75	1	sunitinib

Binding affinities (BindingDB)

35 measured of 35 human assays (36 total across all organisms); most potent 35 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
7-[(E)-but-2-enyl]-3-methyl-8-(3-phenylpropylsulfanyl)purine-2,6-dione	EC50	0.00868 nM
5-((2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-methylsulfonamido)phenylureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)tetrahydrofuran-3-carboxylic acid	IC50	2.8 nM	US-10072034: Kinase inhibitors
2-((2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl) ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethyl)thio)acetic acid	IC50	2.9 nM	US-10072034: Kinase inhibitors
5-((2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl) ureido)naphthalen-1 yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)furan-3-carboxylic acid	IC50	5.6 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl-2-methoxy-3-(methylsulfonamido)phenyl) ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)propanoic acid	IC50	7.3 nM	US-10072034: Kinase inhibitors
5-((2-(3-((4-((4-(3-(5-tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)methyl)thiophene-3-carboxylic acid	IC50	7.3 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy)-3-(methylsulfinyl)phenyl ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	8 nM	US-10072034: Kinase inhibitors
2-[2-[2-[3-[[4-[4-[[5-tert-butyl-3-(methanesulfonamido)-2-methoxyphenyl]carbamoylamino]naphthalen-1-yl]oxy-2-pyridinyl]amino]-5-methoxyphenoxy]ethoxy]ethoxy]propanoic acid	IC50	10.4 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonyl)phenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxphenoxy)ethoxy)ethoxy)acetic acid	IC50	11.7 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(N-methylmethylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	11.7 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl) ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxyethoxy)-2-methylpropanoic acid	IC50	14.4 nM	US-10072034: Kinase inhibitors
5-((2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamidophenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxphenoxy)ethoxy)methyl)thiophene-2-carboxylic acid	IC50	15.3 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-3-(ethylsulfonamido-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	16.3 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl-3-(ethylsulfonyl)-2-methoxyphenyl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenyl)ethoxy)ethoxy)acetic acid	IC50	16.4 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl) isoxazol-3-yl)ureido)naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	17.2 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-tert-Butyl-2-methoxy-3-(methylsulfonamidophenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)-N-(methylsulfonyl)acetamide	IC50	18.1 nM	US-10072034: Kinase inhibitors
1-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethyl-1H-pyrazole-4-carboxylic acid	IC50	18.1 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-(methoxy-d3)-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	19.5 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl-oxy)pyridin-2-yl)amino)-5-(difluoromethoxy)phenoxy)ethoxy)ethoxy)acetic acid	IC50	20.6 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-(4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylcarbamoyl)phenyl)ureido) naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	20.8 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyrimidin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	23 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy)-3-(methylsulfonamido)phenyl)ureido-naphthalen-1-yl)oxy)pyridin-2-yl)amino-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	23 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl-2-methoxy-3-(methylsulfonamido)phenyl) ureido)-naphthalen-1-yl)oxy)pyridin-2 amino)-5-methoxyphenoxy)ethoxy) ethoxy)-N—(N,N-dimethylsulfamoyl)acetamide	IC50	26.3 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-3-(dimethylphosphoryl)-2-methoxyphenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)ethoxy)acetic acid	IC50	26.5 nM	US-10072034: Kinase inhibitors
N-(3-(3-(4-((2-((3-(2-(2-(1H-Tetrazol-5-yl)methoxyethoxy)ethoxy)-5-methoxyphenyl)amino)-pyridin-4-yl)oxy)naphthalen-1-yl)ureido)-5-(tert-butyl)-2-methoxyphenyl)methanesulfonamide	IC50	29.2 nM	US-10072034: Kinase inhibitors
N-(5-(tert-Butl-2-methoxy-3-(3-(4-((2-((3-methoxy-5-(2-(2-((5-oxo-2,5-dihydroisoxazol-3-yl)methoxy)ethoxy)ethoxy)phenyl)amino)pyridin-4-yl)oxy)naphthalen-1-yl)ureido)phenyl)-methanesulfonamide	IC50	29.3 nM	US-10072034: Kinase inhibitors
2-(2-(3-((4-((4-(3-(5-(tert-Buty-2-methoxy-3-(methylsulfonamido)phenyl) ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxyphenoxy)ethoxy)acetic acid	IC50	61.9 nM	US-10072034: Kinase inhibitors
2-(2-(2-(3-((4-((4-(3-(5-(tert-Butyl)-2-methoxy-3-(methylsulfonamido)phenyl)ureido)-naphthalen-1-yl)oxy)pyridin-2-yl)amino)-5-methoxybenzamido)ethoxy)ethoxy)acetic acid, hydrochloride salt	IC50	115 nM	US-10072034: Kinase inhibitors
SMR000523991	IC50	720 nM
3-methyl-7-pentyl-8-(2-phenylethylsulfanyl)purine-2,6-dione	IC50	935 nM
cid_814607	IC50	1220 nM
1-[2-(4-chloranylphenoxy)ethyl]benzimidazol-2-amine	IC50	8600 nM
1-[(4-chlorophenyl)methyl]benzimidazol-2-amine	IC50	12100 nM
MLS-0281326.0001	IC50	13200 nM
SMR000554419	IC50	19800 nM

ChEMBL bioactivities

68 potent at pChembl≥5 of 77 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.55	IC50	2.8	nM	CHEMBL6032444
8.54	IC50	2.9	nM	CHEMBL5765378
8.25	IC50	5.6	nM	CHEMBL5844552
8.14	IC50	7.3	nM	CHEMBL5786724
8.14	IC50	7.3	nM	CHEMBL5747821
8.10	IC50	8	nM	CHEMBL5770282
8.10	IC50	8	nM	DICLOFENAC
8.05	IC50	9	nM	CHEMBL427739
8.00	IC50	10	nM	CHEMBL570538
7.98	IC50	10.4	nM	CHEMBL5786724
7.93	IC50	11.7	nM	CHEMBL6002546
7.93	IC50	11.7	nM	CHEMBL6047011
7.92	IC50	12	nM	CHEMBL553416
7.89	IC50	13	nM	CHEMBL549974
7.89	IC50	13	nM	CHEMBL29804
7.84	IC50	14.4	nM	CHEMBL6016031
7.82	IC50	15.3	nM	CHEMBL5747870
7.79	IC50	16.4	nM	CHEMBL5953948
7.79	IC50	16.3	nM	CHEMBL6050282
7.76	IC50	17.3	nM	CHEMBL5986978
7.76	IC50	17.2	nM	CHEMBL5898824
7.74	IC50	18.1	nM	CHEMBL5762545
7.74	IC50	18.1	nM	CHEMBL5882208
7.72	IC50	19.1	nM	CHEMBL5786724
7.71	IC50	19.5	nM	CHEMBL5945601
7.70	IC50	20	nM	CHEMBL552258
7.70	IC50	20	nM	R-KETOPROFEN
7.69	IC50	20.6	nM	CHEMBL5807419
7.68	IC50	20.8	nM	CHEMBL5803682
7.61	IC50	24.6	nM	CHEMBL5775525
7.60	IC50	25	nM	CHEMBL569366
7.60	IC50	25	nM	CHEMBL77981
7.58	IC50	26.5	nM	CHEMBL5920116
7.58	IC50	26.3	nM	CHEMBL5756624
7.54	IC50	29.2	nM	CHEMBL5755078
7.53	IC50	29.3	nM	CHEMBL5877825
7.30	IC50	50	nM	CHEMBL549973
7.30	IC50	50	nM	(R)-IBUPROPHEN
7.30	IC50	50	nM	INDOMETHACIN
7.21	IC50	61.9	nM	CHEMBL5923363
7.05	IC50	90	nM	TOLMETIN
6.94	IC50	115	nM	CHEMBL5868666
6.40	IC50	400	nM	CHEMBL77823
6.30	IC50	500	nM	CHEMBL541236
6.30	IC50	500	nM	CHEMBL30038
6.26	IC50	550.7	nM	CHEMBL1412853
6.22	IC50	600	nM	CHEMBL559389
6.22	IC50	596	nM	CHEMBL1412853
6.21	IC50	620	nM	CHEMBL1412853
6.19	IC50	650	nM	CHEMBL549975

PubChem BioAssay actives

20 with measured affinity, of 43 total; 20 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
Diclofenac	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0080	uM
2-[2-(2-fluoroanilino)phenyl]acetic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0090	uM
2-[2-(2,6-dichloroanilino)phenyl]propanoic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0100	uM
2-[2-(2,6-dichloroanilino)phenyl]propanamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0120	uM
2-[2-(2-fluorophenoxy)phenyl]acetic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0130	uM
2-[2-(2,6-dichloroanilino)phenyl]-N-methylsulfonylpropanamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0130	uM
(2R)-2-(3-benzoylphenyl)propanoic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0200	uM
2-[2-(2,6-dichloroanilino)phenyl]-N-(2-hydroxyethyl)propanamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0200	uM
2-[2-(2,5-dichloroanilino)phenyl]acetic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0250	uM
2-[2-(2,6-dichloroanilino)phenyl]-N-[3-(dimethylamino)propyl]propanamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0250	uM
(2R)-2-[4-(2-methylpropyl)phenyl]propanoic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0500	uM
Indomethacin	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0500	uM
2-[2-(2-fluorophenoxy)phenyl]-N-methylsulfonylacetamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0500	uM
Tolmetin	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.0900	uM
2-[2-(2-chloroanilino)phenyl]acetic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.4000	uM
2-[2-(2,6-dichloro-3-methylanilino)phenyl]acetic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.5000	uM
2-[2-(2-chlorophenoxy)phenyl]acetic acid	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.5000	uM
2-[2-(2,6-dichloroanilino)phenyl]-N-(2,6-dimethylphenyl)propanamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.6000	uM
N-tert-butyl-2-[2-(2,6-dichloroanilino)phenyl]propanamide	426392: Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	ic50	0.6500	uM
(2R,3S,4S,5R,6R)-6-[2-(2-aminoethoxy)ethoxy]-3-[(2R,3R,4S,5S,6R)-6-carboxy-5-[(2R,3R,4S,5S,6R)-6-carboxy-5-[(2R,3R,4S,5S,6R)-6-carboxy-4-hydroxy-3,5-disulfooxyoxan-2-yl]oxy-4-hydroxy-3-sulfooxyoxan-2-yl]oxy-4-hydroxy-3-sulfooxyoxan-2-yl]oxy-4-hydroxy-5-sulfooxyoxane-2-carboxylic acid	1823527: Binding affinity to human CXCL8 assessed as dissociation constant incubated for 3 mins by surface plasmon resonance analysis	kd	9.3400	uM

CTD chemical–gene interactions

1238 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects binding, decreases expression, increases expression, increases secretion, increases reaction (+5 more)	141
Particulate Matter	increases abundance, affects cotreatment, affects secretion, decreases secretion, affects reaction (+8 more)	102
Vehicle Emissions	increases secretion, increases expression, increases reaction, increases abundance, decreases expression (+5 more)	59
SB 203580	affects reaction, increases reaction, affects cotreatment, decreases secretion, decreases expression (+5 more)	50
Tetradecanoylphorbol Acetate	decreases expression, affects expression, decreases reaction, increases expression, affects cotreatment (+3 more)	42
Resveratrol	increases activity, increases reaction, decreases reaction, increases secretion, decreases secretion (+7 more)	37
Acetylcysteine	decreases reaction, increases expression, increases abundance, affects cotreatment, increases reaction (+3 more)	35
Air Pollutants	increases abundance, affects cotreatment, decreases secretion, affects response to substance, increases secretion (+6 more)	32
Dexamethasone	decreases reaction, decreases expression, increases secretion, increases expression, increases reaction (+4 more)	32
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	decreases reaction, increases secretion, increases phosphorylation, increases expression, decreases response to substance (+3 more)	31
sodium arsenite	increases abundance, decreases reaction, decreases expression, affects expression, increases phosphorylation (+8 more)	29
Tobacco Smoke Pollution	affects expression, decreases expression, increases secretion, affects cotreatment, increases expression (+5 more)	28
nickel sulfate	increases response to substance, affects expression, decreases expression, affects cotreatment, decreases reaction (+5 more)	27
Ozone	increases expression, increases reaction, decreases reaction, increases abundance, increases secretion (+1 more)	25
U 0126	decreases reaction, increases abundance, affects expression, increases secretion, decreases secretion (+6 more)	24
Dinitrochlorobenzene	decreases reaction, increases secretion, affects reaction, increases expression, increases stability (+1 more)	22
Quercetin	decreases secretion, affects expression, decreases reaction, affects secretion, affects cotreatment (+3 more)	22
Mustard Gas	affects reaction, affects expression, increases reaction, increases secretion, decreases reaction (+1 more)	21
pyrazolanthrone	decreases reaction, increases reaction, affects cotreatment, decreases expression, decreases response to substance (+3 more)	20
deoxynivalenol	increases reaction, affects binding, increases activity, increases phosphorylation, increases expression (+6 more)	18
Hydrogen Peroxide	decreases reaction, increases reaction, increases secretion, decreases response to substance, increases expression (+3 more)	18
Tetrachlorodibenzodioxin	affects binding, affects cotreatment, decreases expression, decreases secretion, affects expression (+5 more)	18
Asbestos, Crocidolite	affects reaction, increases secretion, increases expression, affects expression, decreases reaction (+3 more)	18
nickel chloride	decreases reaction, increases expression, increases phosphorylation, increases secretion, affects reaction (+4 more)	17
Benzo(a)pyrene	decreases reaction, increases expression, affects expression, affects cotreatment, decreases abundance (+7 more)	17
Cadmium Chloride	increases expression, affects cotreatment, increases reaction, increases secretion, affects reaction (+2 more)	17
cobaltous chloride	increases secretion, affects cotreatment, increases reaction, decreases activity, decreases reaction (+4 more)	16
Silicon Dioxide	decreases reaction, increases secretion, increases expression, increases reaction, affects reaction	16
3-(4-methylphenylsulfonyl)-2-propenenitrile	increases secretion, increases abundance, increases expression, decreases secretion, decreases reaction	15
lipopolysaccharide, E coli O55-B5	increases expression, increases reaction, increases secretion, decreases secretion, affects reaction (+1 more)	15

ChEMBL screening assays

17 unique, capped per target: 9 functional, 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1052371	Binding	Inhibition of CXCL8-induced chemotaxis in human polymorphonuclear leukocyte pretreated for 15 mins measured after 4 hrs by cell migration assay	Structure-Activity Relationship of novel phenylacetic CXCR1 inhibitors. — Bioorg Med Chem Lett
CHEMBL1614436	Functional	PUBCHEM_BIOASSAY: SAR analysis of Muramyl dipeptide (MDP) induced IL-8 secretion in MCF-7/NOD2 cells - Set 2. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID1566, AID1575, AID1578, AID1579, AID1848, AID1849, A	PubChem BioAssay data set

Cellosaurus cell lines

11 cell lines: 7 transformed cell line, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A8CQ	HEK-Blue-Lucia Null (NF/IL8)	Transformed cell line	Female
CVCL_A8CR	HEK-Blue-Lucia hTLR2 (NF/IL8)	Transformed cell line	Female
CVCL_A8CS	HEK-Blue-Lucia hTLR3 (NF/IL8)	Transformed cell line	Female
CVCL_A8CT	HEK-Blue-Lucia hTLR5 (NF/IL8)	Transformed cell line	Female
CVCL_A8CU	HEK-Blue-Lucia hTLR9 (NF/IL8)	Transformed cell line	Female
CVCL_A8CV	HEK-Blue-Lucia mTLR4 (NF/IL8)	Transformed cell line	Female
CVCL_A8CW	HEK-Blue-Lucia mTLR7 (NF/IL8)	Transformed cell line	Female
CVCL_B0ZD	Abcam PC-3 CXCL8 KO	Cancer cell line	Male
CVCL_D7N8	Ubigene A-549 CXCL8 KO	Cancer cell line	Male
CVCL_D8JQ	Ubigene HCT 116 CXCL8 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00168987	PHASE4	COMPLETED	Influence of an Oral Nutritional Supplement Rich in Omega-3 Fatty Acids on Functional State and Quality of Life in Malnourished Patients With Gastroenterological Tumors
NCT00280709	PHASE4	COMPLETED	Biliary Metal Stent Study: Metal Stents for Management of Distal Malignant Biliary Obstruction
NCT00797121	PHASE4	UNKNOWN	Preoperative Biliary Drainage for Resectable Hilar Cholangiocarcinoma
NCT01111591	PHASE4	UNKNOWN	Cyclooxygenase-2 Inhibitor for Adjuvant Anticancer Effect in Patients With Biliary-pancreas Cancer
NCT01256034	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Pancreaticoduodenectomy
NCT01256047	PHASE4	COMPLETED	Effects of Preoperative Immunonutrition in Patients Undergoing Hepatectomy
NCT01642875	PHASE4	UNKNOWN	Early Oral Versus Enteral Nutrition After Pancreatoduodenectomy
NCT02027311	PHASE4	COMPLETED	Etomidate vs. Midazolam for Sedation During ERCP
NCT02174575	PHASE4	WITHDRAWN	Anesthetic Agents and Acute Kidney Injury After Liver Resection Surgery
NCT07486713	PHASE4	RECRUITING	Olutasidenib DDI Study in Patients With IDH1 Mutation Positive Malignancies
NCT00540735	PHASE3	TERMINATED	Efficiency Evaluation of Photodynamic Therapy With Photofrin® on Unresectable Type III or IV Cholangiocarcinomas
NCT00653978	PHASE3	UNKNOWN	Unilateral Versus Bilateral Stents for Bismuth Type II and III Malignant Hilar Strictures
NCT00809081	PHASE3	UNKNOWN	Early Enteral Feeding After Pylorus Preserving Pancreatoduodenectomy
NCT00869635	PHASE3	COMPLETED	S-1 and Photodynamic Therapy in Cholangiocarcinoma
NCT00907413	PHASE3	TERMINATED	Photodynamic Therapy (PDT) Trial for Palliation of Cholangiocarcinoma
NCT01926236	PHASE3	COMPLETED	Active Symptom Control Alone or With mFOLFOX Chemotherapy for Locally Advanced/ Metastatic Biliary Tract Cancers
NCT02170090	PHASE3	ACTIVE_NOT_RECRUITING	Adjuvant Chemotherapy With Gemcitabine and Cisplatin Compared to Standard of Care After Curative Intent Resection of Biliary Tract Cancer
NCT02548195	PHASE3	UNKNOWN	Oxaliplatin+Gemcitabine vs Capecitabine as Adjuvant Therapy for Intrahepatic Cholangiocarcinoma
NCT02773485	PHASE3	UNKNOWN	Chemo Alone or in Combination With Radiation in Unresectable Cholangiocarcinoma
NCT02853474	PHASE3	COMPLETED	Early Palliative Care in Patients With Metastatic Upper Gastrointestinal Cancers Treated With First-line Chemotherapy
NCT02989857	PHASE3	COMPLETED	Study of AG-120 in Previously Treated Advanced Cholangiocarcinoma With IDH1 Mutations (ClarIDHy)
NCT03656536	PHASE3	TERMINATED	A Study to Evaluate the Efficacy and Safety of Pemigatinib Versus Chemotherapy in Unresectable or Metastatic Cholangiocarcinoma
NCT03773302	PHASE3	TERMINATED	Phase 3 Study of BGJ398 (Oral Infigratinib) in First Line Cholangiocarcinoma With FGFR2 Gene Fusions/Translocations
NCT03779035	PHASE3	UNKNOWN	Adjuvant Chemotherapy for Biliary Tract Cancer After Curative Resection
NCT04093362	PHASE3	TERMINATED	Futibatinib Versus Gemcitabine-Cisplatin Chemotherapy as First-Line Treatment of Patients With Advanced Cholangiocarcinoma Harboring FGFR2 Gene Rearrangements
NCT04157985	PHASE3	COMPLETED	Evaluating Length of Treatment With PD-1/PD-L1 Inhibitor in Advanced Solid Tumors
NCT05823311	PHASE3	RECRUITING	Lenvatinib, Tislelizumab Combined with Gemcitabine and Cisplatin (GPLET) in the Treatment of Advanced Cholangiocarcinoma
NCT05876754	PHASE3	RECRUITING	An Early Access Study of Ivosidenib in Patients With a Pretreated Locally Advanced or Metastatic Cholangiocarcinoma
NCT05948475	PHASE3	RECRUITING	Study of Tinengotinib VS. Physician’s Choice a Treatment of Subjects With FGFR-altered in Cholangiocarcinoma
NCT07155525	PHASE3	RECRUITING	Tissue Adhesive Glue Modified Cyanoacrylate (Glubran® 2) in Soft Pancreas
NCT07328919	PHASE3	NOT_YET_RECRUITING	Efficacy and Safety of TT-00420 (Tinengotinib) Tablets Versus Chemotherapy in Patients With Advanced Intrahepatic Cholangiocarcinoma Harboring FGFR2 Fusions/Rearrangements or Mutations
NCT00286013	PHASE2	COMPLETED	Feasibility of Radiotherapy and Concomitant Gemcitabine and Oxaliplatin in Locally Advanced Pancreatic Cancer and Distal Cholangiocarcinoma
NCT00290316	PHASE2	UNKNOWN	Accuracy of Endoscopic Ultrasound for Detection of Tumors of the Liver
NCT00350753	PHASE2	COMPLETED	Avastin and Tarceva for Upper Gastrointestinal Cancers
NCT00356161	PHASE2	UNKNOWN	HAI Via Interventionally Implanted Port Catheter Systems
NCT00660140	PHASE2	COMPLETED	Study of Gemcitabine and Carboplatin in the Treatment of Metastatic or Recurrent Cholangiocarcinoma/Gallbladder Cancer
NCT00713687	PHASE2	WITHDRAWN	Gemcitabine/Oxaliplatin and Photodynamic Therapy in Cholangiocarcinoma
NCT00779454	PHASE2	COMPLETED	Combined Biological Treatment and Chemotherapy for Patients With Inoperable Cholangiocarcinoma
NCT00832637	PHASE2	TERMINATED	Gemcitabine, Oxaliplatin, Tarceva &/or Cisplatin in HCC & Biliary Tree Cancers
NCT00948935	PHASE2	COMPLETED	Study of Gemcitabine, Irinotecan and Panitumumab in Patients With Advanced and Metastatic Biliary Tract Adenocarcinoma