CXCR2

Summary

CXCR2 (C-X-C motif chemokine receptor 2, HGNC:6027) is a protein-coding gene on chromosome 2q35, encoding C-X-C chemokine receptor type 2 (P25025). Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor.

The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein activated second messenger system. This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. Alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 3579 — RefSeq curated summary.

At a glance

• Gene–disease (curated): WHIM syndrome 2 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 25
• Clinical variants (ClinVar): 245 total — 4 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 7
• Druggable target: yes — 13 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001557

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6027
Approved symbol	CXCR2
Name	C-X-C motif chemokine receptor 2
Location	2q35
Locus type	gene with protein product
Status	Approved
Aliases	CMKAR2, CD182
Ensembl gene	ENSG00000180871
Ensembl biotype	protein_coding
OMIM	146928
Entrez	3579

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 13 protein_coding

ENST00000318507, ENST00000415392, ENST00000418878, ENST00000428565, ENST00000449014, ENST00000453237, ENST00000454148, ENST00000875238, ENST00000875239, ENST00000875240, ENST00000875241, ENST00000939647, ENST00000948534

RefSeq mRNA: 2 — MANE Select: NM_001557 NM_001168298, NM_001557

CCDS: CCDS2408

Canonical transcript exons

ENST00000318507 — 3 exons

Exon	Start	End
ENSE00001219308	218129314	218129365
ENSE00001219313	218126028	218126353
ENSE00001219322	218134777	218137251

Expression profiles

Bgee: expression breadth ubiquitous, 202 present calls, max score 98.77.

FANTOM5 (CAGE): breadth broad, TPM avg 13.6269 / max 4349.1984, expressed in 242 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25279	5.6773	107
25282	3.7102	111
25278	2.8729	112
25280	0.5702	27
25277	0.2311	41
25274	0.1891	57
25281	0.1436	19
25275	0.1182	32
25276	0.1145	17

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
blood	UBERON:0000178	98.77	gold quality
periodontal ligament	UBERON:0008266	95.58	gold quality
granulocyte	CL:0000094	89.92	gold quality
trabecular bone tissue	UBERON:0002483	89.09	gold quality
epithelium of esophagus	UBERON:0001976	88.75	gold quality
esophagus squamous epithelium	UBERON:0006920	88.66	gold quality
leukocyte	CL:0000738	87.43	gold quality
cervix squamous epithelium	UBERON:0006922	87.27	silver quality
monocyte	CL:0000576	86.88	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.87	gold quality
mononuclear cell	CL:0000842	86.66	gold quality
squamous epithelium	UBERON:0006914	86.59	gold quality
spleen	UBERON:0002106	86.47	gold quality
oral cavity	UBERON:0000167	86.35	gold quality
bone marrow	UBERON:0002371	85.66	gold quality
cervix epithelium	UBERON:0004801	85.52	gold quality
gingiva	UBERON:0001828	85.05	gold quality
esophagus mucosa	UBERON:0002469	84.19	gold quality
bone marrow cell	CL:0002092	83.38	gold quality
gingival epithelium	UBERON:0001949	82.87	gold quality
vermiform appendix	UBERON:0001154	82.48	gold quality
lower esophagus mucosa	UBERON:0035834	81.49	gold quality
biceps brachii	UBERON:0001507	81.27	gold quality
decidua	UBERON:0002450	80.13	gold quality
buccal mucosa cell	CL:0002336	79.78	silver quality
hair follicle	UBERON:0002073	79.63	gold quality
palpebral conjunctiva	UBERON:0001812	78.65	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.56	gold quality
mammalian vulva	UBERON:0000997	77.00	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	76.79	silver quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.96
E-MTAB-6379	no	1.08

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPA, HIF1A, NFKB1, NFKB, PPARG, RELA, SPI1, STAT3, USF2

miRNA regulators (miRDB)

38 targeting CXCR2, 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-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-185-3P	99.95	67.01	1743
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-1208	99.70	68.28	1533
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-1287-3P	99.63	66.93	492
HSA-MIR-4743-3P	99.62	68.12	2095
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-548B-3P	99.38	67.26	1000
HSA-MIR-504-3P	99.30	67.18	1745
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4279	99.19	66.70	2437
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-5001-3P	98.91	67.28	1394
HSA-MIR-224-3P	98.91	68.42	1815
HSA-MIR-522-3P	98.91	68.56	1817
HSA-MIR-6829-5P	98.86	65.12	1480
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-12114	98.70	63.45	730
HSA-MIR-654-3P	98.38	67.61	905
HSA-MIR-1304-3P	98.29	66.44	1207
HSA-MIR-10226	98.25	66.50	811
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-337-3P	97.90	69.37	1052

Literature-anchored findings (GeneRIF, showing 40)

• Phagocytosing neutrophils down-regulate its expression (PMID:12239185)
• CXCR1 and CXCR2 internalization and recycling are tightly regulated by receptor domains and by actin-related kinases. (PMID:12442335)
• role in mediating angiogenic effects of interleukin effects in intestinal microvascular endothelial cells (PMID:12496258)
• Neutrophil recruitment to inflammatory sites is mediated by two related receptors: CXCR1 and CXCR2. Both receptors share two ligands, interleukin-8 (CXCL8) and GCP-2 (CXCL6). (PMID:12628493)
• functions as a dimer and truncated receptors negatively modulate receptor activities competing for the formation of wild type dimers (PMID:12888558)
• a potentiation of Ins(1,4,5)P3 generation in the presence of coactivation of P2Y2 nucleotide receptors and CXCR2 would be sufficient for additional Ca2+ release. (PMID:12975484)
• the data suggest that constitutive expression of CXCR1 and CXCR2 play an important role regulating the IL-8-mediated metastatic phenotype in human malignant melanoma cells. (PMID:14713106)
• neutrophil migration in response to CXCR1 or CXCR2 agonists is not dependent on endocytosis of CXCR1 or CXCR2 (PMID:15028716)
• extra- and intracellular CXCR1 and CXCR2 are differentially expressed and regulated on T lymphocytes and mast cells (PMID:15265017)
• The results support the hypothesis of bacterial propagation through CXCR2 neutrophil recruitment and confirm that tissue injury is unrelated to A. phagocytophilum tissue load. (PMID:15358660)
• Arrestin has a role in regulating MAPK activation and preventing NADPH oxidase-dependent death of cells expressing CXCR2 (PMID:15364949)
• IL-8 and CXCR2 participate in the altered megakarocyte growth that features myeloid metaplasia with myelofibrosis (PMID:15454487)
• membrane-bound activated Cdc42 and Rac1 localize to the leading edge of cells expressing wild-type CXCR2 receptor, but not in cells expressing mutant CXCR2 (PMID:15479720)
• Activation of neutrophils and down-regulation of CXCR2 were predominantly caused by IL-8 (PMID:15545821)
• In eutopic endometrium of women with endometriosis, significant increase in both proliferative and secretory phases for epithelial CXCR2 expression, and in proliferative phase for CXCR1 expression. May be involved in pathogenesis of endometriosis. (PMID:15618253)
• neutrophils from transgenic mice were found to express hCXCR2 and to respond to CMV vCXCL-1 (PMID:15626158)
• the relative expression levels of CXCR-1 and -2 mRNA were rather lower than expected in the affected esophageal mucosa of patients with reflux esophagitis (PMID:15793866)
• CXCR1-CXCR2 heterodimers are as likely to form in cells co-expressing these two chemokine receptors as the corresponding homodimers. (PMID:15946947)
• We propose that the concurrence of CXCR2 on oligodendrocytes and induced CXCL1 on hypertrophic astrocytes in MS provides a novel mechanism for recruitment of oligodendrocytes to areas of damage, an essential prerequisite for lesion repair. (PMID:16086366)
• Gene polymorphisms active in the EGFR pathway may be associated with the sensitivity of colorectal cancer patients to platinum-based chemotherapy. (PMID:16098254)
• neutrophil migration induced by artocarpin involves binding to CXCR2 (PMID:16260092)
• increased expression of ELR+ CXC chemokines and their interaction with CXCR2 plays an important role in the pathogenesis of post-lung transplantation cold ischemia-reperfusion injury (PMID:16272353)
• in CXCR2-expressing cells FAK phosphorylation was adhesion-dependent and was stimulated by fibronectin.Overall, several aspects of CXCL8-induced FAK phosphorylation and migration are regulated in a receptor-specific manner. (PMID:16406804)
• No significant association existed between CXCR2 +1208 C/T polymorphism and multiple sclerosis susceptibility. (PMID:16793206)
• CXCR-1 and CXCR-2 chemokine receptors of synovial fluid neutrophils may have diverse functions in the course of inflammatory arthritides (PMID:16987681)
• analysis of the LLKIL motif in CXCR2, which is required for full IL-8 ligand-induced activation of Erk, Akt, and chemotaxis in HL60 cells (PMID:16990258)
• TNF-alpha and IL-1beta enhance IL-8 expression in term decidual cells, suggesting that these cytokines are important regulators of chorioamnionitis-related decidual neutrophil infiltration. (PMID:17003486)
• most circulating human CD4+ T cells store the inflammatory chemokine receptors CXCR3 and CXCR1 within a distinct intracellular compartment (PMID:17142783)
• data herein indicate that the second extracellular loop (2ECL) of the receptors CXCR1,CXCR2, and CXCL8 is critical for the distinct rate of internalization of each (PMID:17204468)
• CXCR2 receptor is important the homing of circulating endothelial progenitor cells. (PMID:17272812)
• Mesenchymal stem cells express chemokine receptor CXCR2 and migrate upon stimulation with IL-8. (PMID:17295203)
• By activating CXCR2, macrophage migration inhibitory factordisplays chemokine-like functions and acts as a major regulator of inflammatory cell recruitment and atherogenesis. (PMID:17435771)
• Findings indicate that beta-endorphin and Met-enkephalin are contained in primary granules of PMN, and that CXCR1/2 ligands induce p38-dependent translocation and release of these opioid peptides to inhibit inflammatory pain (PMID:17604950)
• The N-loop residues in IL-8 (H18 and F21) and the receptor N-termini are the major structural determinants regulating the rate of receptor internalization, which in turn controlls the activation profile of ERK1/2. (PMID:17630697)
• CXCR2 +1208C/T polymorphism may affect the disease progression. (PMID:17949231)
• Intracellular cross-talk between the GPCR CXCR1 and CXCR2: role of carboxyl terminus phosphorylation sites (PMID:17996233)
• Cyr61 promotes interleukin-8-dependent chemotaxis, transendothelial migration, and intravasation by induction of CXCR1/CXCR2 through integrin alphavbeta3/Src/PI3K/Akt-dependent pathway. (PMID:18025257)
• CXCR2 signaling promotes liver cyst growth in autosomal dominant polycystic kidney disease. (PMID:18199703)
• Abnormal CXCR2 modulation and impaired expression cause systemic lupus erythematosis-neutrophil hyporesponsiveness to IL-8 stimulation in vitro. (PMID:18208820)
• The allergen-induced levels of beta(c) mRNA and CCR3 mRNA in sputum-derived cells were inhibited by TPI ASM8, with no significant effects on the cell surface protein expression of CCR3 and beta(c). (PMID:18244953)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcr2	ENSDARG00000054975
mus_musculus	Cxcr2	ENSMUSG00000026180
rattus_norvegicus	Cxcr2	ENSRNOG00000063618

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-X-C chemokine receptor type 2 — P25025 (reviewed: P25025)

Alternative names: CDw128b, GRO/MGSA receptor, High affinity interleukin-8 receptor B, IL-8 receptor type 2

All UniProt accessions (7): C9J1J7, C9J2F9, C9JG19, C9JW47, P25025, Q53PC4, Q6LCZ7

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for interleukin-8 which is a powerful neutrophil chemotactic factor. Binding of IL-8 to the receptor causes activation of neutrophils. This response is mediated via a G-protein that activates a phosphatidylinositol-calcium second messenger system. Binds to IL-8 with high affinity. Also binds with high affinity to CXCL3, GRO/MGSA and NAP-2. Involved in the homeostatic wound healing response to tissue injury, a multistep cascade that guides neutrophil migration to necrotic sites while avoiding collateral damage of healthy tissues. Signals intravascular neutrophil chemotaxis to the injury site.

Subunit / interactions. Interacts with IL8. Interacts with GNAI2.

Subcellular location. Cell membrane.

Post-translational modifications. Phosphorylated upon ligand binding; which is required for desensitization. (Microbial infection) Proteolytically cleaved by Staphylococcus aureus staphopain A/SspP. This cleavage inhibits CXCR2-dependent neutrophil activation and chemotaxis.

Disease relevance. WHIM syndrome 2 (WHIMS2) [MIM:619407] An autosomal recessive form of WHIM syndrome, a primary immunodeficiency disorder characterized by warts, hypogammaglobulinemia, infections, and myelokathexis. Myelokathexis is a unique form of non-cyclic severe congenital neutropenia caused by accumulation of mature and degenerating neutrophils in the bone marrow. Monocytopenia and lymphopenia, especially B lymphopenia, also commonly occur. There is significant phenotypic variation among patients, such that some individuals may have an incomplete form of the disorder in which one or more of the classic tetrad features are not present. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the G-protein coupled receptor 1 family.

RefSeq proteins (2): NP_001161770, NP_001548* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000057	Chemokine_CXCR2	Family
IPR000174	Chemokine_CXCR_1/2	Family
IPR000276	GPCR_Rhodpsn	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (45 total): helix 14, topological domain 8, transmembrane region 7, strand 5, modified residue 4, turn 2, chain 1, site 1, glycosylation site 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

20 structures.

PDB	Method	Resolution (Å)
4Q3H	X-RAY DIFFRACTION	1.44
6KVA	X-RAY DIFFRACTION	2.2
5TYT	X-RAY DIFFRACTION	2.4
6KVF	X-RAY DIFFRACTION	2.79
8XXH	ELECTRON MICROSCOPY	2.8
8XX6	ELECTRON MICROSCOPY	2.99
8XWS	ELECTRON MICROSCOPY	3.06
8XWV	ELECTRON MICROSCOPY	3.07
8XVU	ELECTRON MICROSCOPY	3.09
8XXR	ELECTRON MICROSCOPY	3.17
8XXX	ELECTRON MICROSCOPY	3.17
6LFL	X-RAY DIFFRACTION	3.2
8XWN	ELECTRON MICROSCOPY	3.29
8XX7	ELECTRON MICROSCOPY	3.32
8XX3	ELECTRON MICROSCOPY	3.38
6LFO	ELECTRON MICROSCOPY	3.4
8XWA	ELECTRON MICROSCOPY	3.48
6LFM	ELECTRON MICROSCOPY	3.5
8XWF	ELECTRON MICROSCOPY	3.65
8XWM	ELECTRON MICROSCOPY	3.71

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25025-F1	79.62	0.33

Antibody-complex structures (SAbDab): 10 — 6KVA, 6KVF, 6LFM, 6LFO, 8XWV, 8XX3, 8XX6, 8XXH, 8XXR, 8XXX

Functional residue map

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

Catalytic / active sites (1): 35–36 ((microbial infection) cleavage; by staphylococcus aureus/sspp)

Post-translational modifications (4): 347, 351, 352, 353

Disulfide bonds (1): 119–196

Glycosylation sites (1): 22

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-6798695	Neutrophil degranulation

MSigDB gene sets: 229 (showing top): REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_SECRETORY_GRANULE, GOCC_CELL_SURFACE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, GOBP_LEUKOCYTE_CHEMOTAXIS, BROWNE_HCMV_INFECTION_48HR_DN, GOBP_TAXIS, YOKOE_CANCER_TESTIS_ANTIGENS, GOBP_LEUKOCYTE_MIGRATION

GO Biological Process (18): dendritic cell chemotaxis (GO:0002407), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cellular defense response (GO:0006968), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), positive regulation of cell population proliferation (GO:0008284), calcium-mediated signaling (GO:0019722), neutrophil chemotaxis (GO:0030593), receptor internalization (GO:0031623), interleukin-8-mediated signaling pathway (GO:0038112), neutrophil activation (GO:0042119), negative regulation of apoptotic process (GO:0043066), G protein-coupled receptor signaling pathway (GO:0007186), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (8): interleukin-8 receptor activity (GO:0004918), G protein-coupled receptor activity (GO:0004930), C-C chemokine receptor activity (GO:0016493), C-X-C chemokine receptor activity (GO:0016494), C-C chemokine binding (GO:0019957), interleukin-8 binding (GO:0019959), chemokine receptor activity (GO:0004950), protein binding (GO:0005515)

GO Cellular Component (9): nucleoplasm (GO:0005654), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), secretory granule membrane (GO:0030667), mast cell granule (GO:0042629), mitotic spindle (GO:0072686)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	3
cellular anatomical structure	3
defense response	2
signal transduction	2
cytokine-mediated signaling pathway	2
chemokine receptor activity	2
C-X-C chemokine binding	2
chemokine binding	2
leukocyte chemotaxis	1
dendritic cell migration	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
phospholipase C activator activity	1
regulation of biological quality	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
intracellular signaling cassette	1
granulocyte chemotaxis	1
neutrophil migration	1
receptor-mediated endocytosis	1
cellular response to interleukin-8	1
granulocyte activation	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
G protein-coupled receptor activity	1
cellular response to chemokine	1
C-X-C chemokine receptor activity	1
interleukin-8 binding	1
interleukin-8-mediated signaling pathway	1
transmembrane signaling receptor activity	1
C-C chemokine binding	1

Protein interactions and networks

STRING

2616 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCR2	CXCL8	P10145	999
CXCR2	CXCL1	P09341	999
CXCR2	CXCL5	P42830	998
CXCR2	CXCL2	P19875	998
CXCR2	CXCL3	P19876	997
CXCR2	CXCL6	P80162	996
CXCR2	PPBP	P02775	996
CXCR2	CXCL12	P48061	996
CXCR2	CCL2	P13500	994
CXCR2	CCL5	P13501	993
CXCR2	CD74	P04233	992
CXCR2	CXCL13	O43927	992
CXCR2	MIF	P14174	991
CXCR2	CXCR4	P30991	984
CXCR2	CD44	P16070	982

IntAct

73 interactions, top by confidence:

A	B	Type	Score
CXCR2	IQGAP1	psi-mi:“MI:0915”(physical association)	0.680
CXCR2	IQGAP1	psi-mi:“MI:0407”(direct interaction)	0.680
IQGAP1	CXCR2	psi-mi:“MI:0914”(association)	0.680
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
CXCR2	EMP1	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	ATP13A1	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	SMCO4	psi-mi:“MI:0915”(physical association)	0.560
TUSC5	CXCR2	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	FKBP8	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	CLDN22	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	TMEM147	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	ARLN	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	TMEM80	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	SLC39A2	psi-mi:“MI:0915”(physical association)	0.560
CXCR2	SLC18A2	psi-mi:“MI:0915”(physical association)	0.560
CD74	CXCR2	psi-mi:“MI:0915”(physical association)	0.520
CXCR2	GPR17	psi-mi:“MI:0915”(physical association)	0.520
GPR17	CXCR2	psi-mi:“MI:0915”(physical association)	0.520
CXCR2	Cd74	psi-mi:“MI:0403”(colocalization)	0.460

BioGRID (28): RAB11FIP2 (Affinity Capture-Western), MYO5B (Affinity Capture-Western), CXCR2 (Affinity Capture-MS), CXCR2 (Affinity Capture-Western), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), CXCR2 (Two-hybrid), TUSC5 (Two-hybrid)

ESM2 similar proteins: A4FUQ5, B1PHQ8, B9VR26, O35786, O70129, O88536, O88537, O97571, P0C7U4, P0C7U5, P21109, P21730, P25024, P25025, P25089, P25090, P30992, P30993, P32248, P33766, P35344, P35407, P51686, P55919, P55920, P79175, P79177, P79188, P79189, P79190, P79191, P79234, P79235, P79236, P79237, P79240, P79242, P79243, P97468, P97520

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

9 interactions.

A	Effect	B	Mechanism
CXCL8	up-regulates	CXCR2	binding
CXCL1	“up-regulates activity”	CXCR2	binding
CXCL2	“up-regulates activity”	CXCR2	binding
CXCL3	“up-regulates activity”	CXCR2	binding
CXCL5	“up-regulates activity”	CXCR2	binding
GRK6	“down-regulates quantity”	CXCR2	phosphorylation
MIF	“up-regulates activity”	CXCR2	binding
GRK2	“down-regulates activity”	CXCR2	phosphorylation
PPARG	“up-regulates quantity by expression”	CXCR2	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 27 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
receptor internalization	5	81.0×	1e-06
positive regulation of gene expression	6	11.6×	7e-04
G protein-coupled receptor signaling pathway	5	9.1×	3e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	2
Uncertain significance	123
Likely benign	100
Benign	12

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
1177051	NM_001557.4(CXCR2):c.968del (p.His323fs)	Pathogenic
1372109	NM_001557.4(CXCR2):c.550C>T (p.Arg184Ter)	Pathogenic
1914495	NM_001557.4(CXCR2):c.662del (p.Ile221fs)	Pathogenic
2806228	NM_001557.4(CXCR2):c.306del (p.Ile103fs)	Pathogenic
1339556	NM_001557.4(CXCR2):c.623G>A (p.Arg208Gln)	Likely pathogenic
809152	NM_001557.4(CXCR2):c.472A>T (p.Lys158Ter)	Likely pathogenic

SpliceAI

342 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218126350:GCAG:G	donor_gain	0.9900
2:218126354:GTAG:G	donor_loss	0.9900
2:218129366:G:GG	donor_gain	0.9800
2:218134772:TATA:T	acceptor_loss	0.9800
2:218134775:A:C	acceptor_loss	0.9800
2:218126354:G:GG	donor_gain	0.9700
2:218126206:G:GT	donor_gain	0.9600
2:218134776:GGTCA:G	acceptor_gain	0.9600
2:218126097:G:GT	donor_gain	0.9500
2:218132941:G:GC	acceptor_gain	0.9500
2:218134775:AGGT:A	acceptor_gain	0.9500
2:218126134:C:CG	donor_gain	0.9400
2:218134774:TAGG:T	acceptor_gain	0.9400
2:218134775:A:AG	acceptor_gain	0.9400
2:218134776:G:GG	acceptor_gain	0.9400
2:218134773:ATAGG:A	acceptor_gain	0.9000
2:218127858:C:G	donor_gain	0.8800
2:218134772:TATAG:T	acceptor_gain	0.8800
2:218127882:TCA:T	donor_gain	0.8700
2:218126167:G:GT	donor_gain	0.8500
2:218127839:T:TA	donor_gain	0.8500
2:218127840:A:AA	donor_gain	0.8500
2:218134776:GGT:G	acceptor_gain	0.8500
2:218126743:GTC:G	donor_gain	0.8300
2:218126744:TCT:T	donor_gain	0.8300
2:218129311:TAGG:T	acceptor_gain	0.8300
2:218131007:GGATT:G	donor_gain	0.8300
2:218130982:C:G	donor_gain	0.8100
2:218126351:CAGGT:C	donor_gain	0.8000
2:218126352:AGGTA:A	donor_gain	0.8000

AlphaMissense

2337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218135222:A:C	S141R	0.997
2:218135224:T:A	S141R	0.997
2:218135224:T:G	S141R	0.997
2:218135579:T:C	F260L	0.996
2:218135581:C:A	F260L	0.996
2:218135581:C:G	F260L	0.996
2:218135762:T:C	F321L	0.996
2:218135764:T:A	F321L	0.996
2:218135764:T:G	F321L	0.996
2:218134985:A:C	S62R	0.994
2:218134987:C:A	S62R	0.994
2:218134987:C:G	S62R	0.994
2:218135137:G:C	W112C	0.994
2:218135137:G:T	W112C	0.994
2:218135156:T:A	C119S	0.994
2:218135157:G:C	C119S	0.994
2:218135135:T:A	W112R	0.992
2:218135135:T:C	W112R	0.992
2:218135232:G:C	R144P	0.992
2:218135195:A:C	S132R	0.991
2:218135197:T:A	S132R	0.991
2:218135197:T:G	S132R	0.991
2:218135598:C:A	P266H	0.991
2:218134999:C:A	N66K	0.990
2:218134999:C:G	N66K	0.990
2:218135157:G:A	C119Y	0.990
2:218135309:T:A	W170R	0.990
2:218135309:T:C	W170R	0.990
2:218134994:G:A	G65R	0.989
2:218134994:G:C	G65R	0.989

dbSNP variants (sampled 300 via entrez): RS1000203679 (2:218134137 T>C), RS1000470944 (2:218125923 G>A), RS1000720972 (2:218134456 T>C), RS1000821382 (2:218133443 G>C), RS1001053646 (2:218129040 C>T), RS1001284150 (2:218137638 T>A,C), RS1001387154 (2:218130436 G>A), RS1001422820 (2:218131609 A>ACCACCC), RS1001452202 (2:218123734 T>C), RS1001633406 (2:218123914 C>A), RS1002216330 (2:218136387 T>C), RS1002394935 (2:218129873 A>G), RS1002555416 (2:218123528 A>G), RS1002610928 (2:218131641 T>C), RS1002737558 (2:218136710 G>A,T)

Disease associations

OMIM: gene MIM:146928 | disease phenotypes: MIM:619407

GenCC curated gene-disease

Disease	Classification	Inheritance
WHIM syndrome 2	Strong	Autosomal recessive
autosomal recessive severe congenital neutropenia due to CXCR2 deficiency	Moderate	Autosomal recessive

Mondo (2): WHIM syndrome 2 (MONDO:0030374), autosomal recessive severe congenital neutropenia due to CXCR2 deficiency (MONDO:0018487)

Orphanet (0):

HPO phenotypes

7 total (7 of 7 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0001636	Tetralogy of Fallot
HP:0011463	Childhood onset
HP:0031160	Myelokathexis
HP:0032169	Severe infection
HP:0034284	Recurrent gingivitis
HP:0410252	Persistently decreased total neutrophil count

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000964_14	Ulcerative colitis	1.000000e-10
GCST001725_74	Inflammatory bowel disease	4.000000e-12
GCST001896_9	Smooth-surface caries	2.000000e-06
GCST004131_76	Inflammatory bowel disease	2.000000e-07
GCST004608_63	Granulocyte percentage of myeloid white cells	1.000000e-20
GCST004609_101	Monocyte percentage of white cells	5.000000e-11
GCST004610_51	White blood cell count	6.000000e-32
GCST004613_84	Sum neutrophil eosinophil counts	2.000000e-41
GCST004614_134	Granulocyte count	8.000000e-42
GCST004620_49	Sum basophil neutrophil counts	4.000000e-42
GCST004626_22	Myeloid white cell count	3.000000e-40
GCST004629_27	Neutrophil count	7.000000e-42
GCST004632_138	Lymphocyte percentage of white cells	3.000000e-20
GCST004633_111	Neutrophil percentage of white cells	3.000000e-25
GCST005537_4	Chronic inflammatory diseases (ankylosing spondylitis, Crohn’s disease, psoriasis, primary sclerosing cholangitis, ulcerative colitis) (pleiotropy)	2.000000e-11
GCST90002389_136	Lymphocyte percentage of white cells	8.000000e-66
GCST90002389_137	Lymphocyte percentage of white cells	1.000000e-11
GCST90002394_22	Monocyte percentage of white cells	1.000000e-27
GCST90002398_111	Neutrophil count	5.000000e-127
GCST90002398_112	Neutrophil count	4.000000e-09
GCST90002398_113	Neutrophil count	6.000000e-21
GCST90002399_124	Neutrophil percentage of white cells	9.000000e-74
GCST90002399_125	Neutrophil percentage of white cells	5.000000e-14
GCST90002407_34	White blood cell count	1.000000e-95
GCST90002407_35	White blood cell count	3.000000e-14

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2096909 (PROTEIN FAMILY), CHEMBL2434 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

13 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 76,643 (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
CHEMBL175	DEXIBUPROFEN	4	12,118
CHEMBL75435	DEXKETOPROFEN	4	5,327
CHEMBL11359	CISPLATIN	4
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL191413	REPARIXIN	3	653
CHEMBL189475	LADARIXIN	3	187
CHEMBL216981	NAVARIXIN ANHYDROUS	2	932
CHEMBL2178579	ELUBRIXIN	2	251
CHEMBL2349310	AZD-8797	2	57
CHEMBL3039531	DANIRIXIN	2	357
CHEMBL4297480	SX-682	2	300
CHEMBL5095217	VIMNERIXIN	2	126
CHEMBL427526	(R)-IBUPROPHEN	1	17,724

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2230054	CXCR2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (21 total), top 21:

Ligand	Action	Affinity	Parameter
navarixin	Antagonist	10.31	pIC50
CXCL1	Full agonist	9.7	pKi
CXCL8	Full agonist	9.5	pKi
[125I]CXCL8 (human)	Full agonist	9.4	pKd
CXCL7	Full agonist	9.3	pIC50
CXCL3	Full agonist	9.2	pIC50
AZD5069	Antagonist	9.1	pIC50
CXCL2	Full agonist	9.1	pIC50
CXCL5	Full agonist	9.0	pIC50
CXCL1	Full agonist	8.8	pKi
[125I]KC-Tyr	Full agonist	8.4	pKd
Mz438		8.38	pKd
vCXCL1	Agonist	8.25	pIC50
danirixin	Antagonist	7.9	pIC50
SB 225002	Antagonist	7.7	pIC50
elubirixin	Antagonist	7.66	pIC50
SX-517	Antagonist	7.22	pIC50
CXCL6	Full agonist	7.0	pKd
HIV-1 matrix protein p17	Agonist	6.89	pKd
reparixin	Negative	6.4	pIC50
NSC 157449	Antagonist	6.3	pIC50

Binding affinities (BindingDB)

101 measured of 223 human assays (223 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
methyl 5-[2-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanyl]acetyl]-1,2-oxazole-3-carboxylate	IC50	14 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
USRE47267, Compound 137	IC50	14 nM	US-RE47267
6-[2-(4-chloro-3-nitrophenyl)-2-oxoethyl]sulfanyl-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	16 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
3-[4-chloro-2-hydroxy-3-(4-methylpiperazin-1-yl)sulfonylanilino]-4-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]cyclobutane-1,2-dione	IC50	30 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[2-[[5-[(5-fluoro-2-pyridinyl)carbamoyl]-2-pyridinyl]oxymethyl]phenyl]boronic acid	IC50	32 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
USRE47267, Compound 168	IC50	32 nM	US-RE47267
2-hydroxy-N-methyl-3-[[2-[[(S)-(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]-N-(2,2,2-trifluoroethyl)benzamide	IC50	36 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[2-[[5-[(4-fluoro-2-hydroxyphenyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	37 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
[2-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	38 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
methyl 2-[[2-hydroxy-3-[[2-[[(S)-(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzoyl]-methylamino]acetate	IC50	42 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
methyl (2R)-1-[2-hydroxy-3-[[2-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzoyl]pyrrolidine-2-carboxylate	IC50	43 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[4-fluoro-2-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	52 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
N-(4-fluorophenyl)-6-[[2-(2,9,9-trimethyl-3,5-dioxa-4-boratricyclo[6.1.1.02,6]decan-4-yl)phenyl]methylsulfanyl]pyridine-3-carboxamide	IC50	59 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
N-(4-fluorophenyl)-6-[[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethoxy)phenyl]methylsulfanyl]pyridine-3-carboxamide	IC50	72 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
[2-[[5-[(4-fluorophenyl)-(pyridin-2-ylmethyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	78 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
[2-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]-4-methoxyphenyl]boronic acid	IC50	79 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
5-[2-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanyl]acetyl]-1,2-oxazole-3-carboxylate	IC50	81 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
USRE47267, Compound 138	IC50	81 nM	US-RE47267
2-hydroxy-N-methyl-3-[[2-[[(S)-(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]-N-(2,2,2-trifluoroethyl)benzamide	IC50	85 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[2-[[5-[(4-hydroxyphenyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	105 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
methyl (2R)-1-[2-hydroxy-3-[[2-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzoyl]pyrrolidine-2-carboxylate	IC50	108 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
N-(4-fluorophenyl)-6-[[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methylsulfanyl]pyridine-3-carboxamide	IC50	112 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-chloro-2-hydroxy-N,N-dimethyl-3-[[2-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzamide	IC50	113 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[2-[[5-[(5-fluoro-2-pyridinyl)carbamoyl]pyrimidin-2-yl]sulfanylmethyl]phenyl]boronic acid	IC50	116 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
USRE47267, Compound 167	IC50	116 nM	US-RE47267
[2-[[3-chloro-5-[(5-fluoro-2-pyridinyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	166 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
USRE47267, Compound 170	IC50	166 nM	US-RE47267
methyl (2S)-1-[2-hydroxy-3-[[2-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]benzoyl]pyrrolidine-2-carboxylate	IC50	171 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
N-(4-fluorophenyl)-6-[[2-(2H-tetrazol-5-yl)phenyl]methylsulfanyl]pyridine-3-carboxamide	IC50	173 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-[2-(2,3-dihydro-1,4-benzodioxin-6-yl)-2-oxoethyl]sulfanyl-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	194 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-[2-(3-chlorophenyl)-2-oxoethyl]sulfanyl-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	210 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-(2,1,3-benzoxadiazol-5-ylmethylsulfanyl)-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	216 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
N-(4-fluorophenyl)-6-[[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]methylsulfanyl]pyridine-3-carboxamide	IC50	275 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
[2-[[5-[[4-(trifluoromethoxy)phenyl]carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	278 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
[2-[[5-[(5-fluoro-2-pyridinyl)carbamoyl]-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	294 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-(3,4-dihydro-2H-1,5-benzodioxepin-6-ylmethylsulfanyl)-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	350 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
3-[(2-hydroxy-1-methyl-2H-pyridin-3-yl)amino]-4-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]cyclobutane-1,2-dione	IC50	384 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[2-[2-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanyl]ethyl]phenyl]boronic acid	IC50	387 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-benzylsulfanyl-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	393 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
2-hydroxy-N,N-dimethyl-3-[[2-[[(5-methylfuran-2-yl)-[(2S)-oxolan-2-yl]methyl]amino]-3,4-dioxocyclobutyl]amino]benzamide	IC50	483 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
2-hydroxy-N-methyl-3-[[2-[[(R)-(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]-N-(2,2,2-trifluoroethyl)benzamide	IC50	508 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
[2-[[5-(pyridin-4-ylcarbamoyl)-2-pyridinyl]sulfanylmethyl]phenyl]boronic acid	IC50	520 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
6-[2-(5-bromo-2,3-dihydro-1-benzofuran-7-yl)-2-oxoethyl]sulfanyl-N-(4-fluorophenyl)pyridine-3-carboxamide	IC50	529 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
N-(4-fluorophenyl)-6-(oxolan-2-ylmethylsulfanyl)pyridine-3-carboxamide	IC50	542 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
methyl (2S)-1-[2-fluoro-3-[[2-[[(5-methylfuran-2-yl)-[(2R)-thiolan-2-yl]methyl]amino]-3,4-dioxocyclobutyl]amino]benzoyl]pyrrolidine-2-carboxylate	IC50	552 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
methyl 2-[[2-[2-hydroxy-3-[[2-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-3,4-dioxocyclobutyl]amino]phenyl]-2-oxoethyl]amino]acetate	IC50	580 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
2-methyl-2-[[7-(3-phenylpropoxy)-1-benzothiophene-6-carbonyl]amino]propanoic acid	IC50	600 nM	US-8980938: CXCR2 inhibitors
N-(4-fluorophenyl)-6-[2-[2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethylsulfanyl]pyridine-3-carboxamide	IC50	611 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators
3-[[(5-methylfuran-2-yl)-(thiolan-2-yl)methyl]amino]-4-[(2-oxo-1H-pyridin-3-yl)amino]cyclobutane-1,2-dione	IC50	652 nM	US-9388149: Disubstituted 3,4-diamino-3-cyclobutene-1,2-dione compounds for use in the treatment of chemokine-mediated diseases
4-[[5-[(4-fluorophenyl)carbamoyl]-2-pyridinyl]sulfanyl]butylboronic acid	IC50	689 nM	US-8981106: Pyrimidinecarboxamides as CXCR2 modulators

ChEMBL bioactivities

1410 potent at pChembl≥5 of 1462 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.31	IC50	0.049	nM	NAVARIXIN ANHYDROUS
10.31	Kd	0.049	nM	CHEMBL218115
10.31	Kd	0.049	nM	NAVARIXIN ANHYDROUS
10.30	Kd	0.05012	nM	NAVARIXIN ANHYDROUS
10.22	Ki	0.06	nM	NAVARIXIN ANHYDROUS
10.00	IC50	0.1	nM	CHEMBL4442431
9.92	IC50	0.12	nM	CHEMBL577075
9.80	IC50	0.1585	nM	CHEMBL4066904
9.70	IC50	0.1995	nM	CHEMBL4098864
9.70	IC50	0.1995	nM	CHEMBL4082136
9.62	IC50	0.24	nM	CHEMBL4128926
9.61	Ki	0.2455	nM	CHEMBL4562140
9.60	IC50	0.2512	nM	CHEMBL4072270
9.60	IC50	0.2512	nM	CHEMBL4062361
9.60	IC50	0.2512	nM	CHEMBL4060139
9.50	IC50	0.3162	nM	CHEMBL3818984
9.50	IC50	0.3162	nM	CHEMBL3818853
9.50	IC50	0.3162	nM	CHEMBL3819480
9.50	IC50	0.3162	nM	CHEMBL4077201
9.40	IC50	0.3981	nM	CHEMBL3819163
9.40	IC50	0.3981	nM	CHEMBL3818581
9.40	IC50	0.3981	nM	CHEMBL3817901
9.40	IC50	0.3981	nM	CHEMBL4070506
9.40	IC50	0.3981	nM	CHEMBL4086957
9.40	IC50	0.3981	nM	CHEMBL4066818
9.30	IC50	0.5012	nM	CHEMBL3819295
9.30	IC50	0.5012	nM	CHEMBL3817901
9.30	IC50	0.5012	nM	CHEMBL3819569
9.30	IC50	0.5012	nM	CHEMBL3818793
9.30	IC50	0.5012	nM	CHEMBL3819512
9.30	IC50	0.5012	nM	CHEMBL3818277
9.30	IC50	0.5012	nM	CHEMBL3818827
9.30	IC50	0.5012	nM	CHEMBL3819221
9.30	IC50	0.5012	nM	CHEMBL4066510
9.30	IC50	0.5012	nM	CHEMBL4088551
9.30	IC50	0.5012	nM	CHEMBL4103349
9.30	IC50	0.5012	nM	CHEMBL4082031
9.22	Ki	0.6	nM	CHEMBL396573
9.20	IC50	0.631	nM	CHEMBL3818458
9.20	IC50	0.631	nM	CHEMBL3818216
9.20	IC50	0.631	nM	CHEMBL4098979
9.20	IC50	0.631	nM	CHEMBL4079102
9.19	Ki	0.6457	nM	NAVARIXIN ANHYDROUS
9.15	IC50	0.7	nM	LADARIXIN
9.10	IC50	0.7943	nM	CHEMBL3819542
9.10	IC50	0.7943	nM	CHEMBL3818917
9.10	IC50	0.7943	nM	CHEMBL3818820
9.10	IC50	0.7943	nM	CHEMBL4089421
9.10	Ki	0.8	nM	CHEMBL246318
9.00	IC50	1	nM	REPARIXIN

PubChem BioAssay actives

1141 with measured affinity, of 1765 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
3-[[2-[[(1R)-1-(furan-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide	1915498: Binding affinity to human CXCR2 assessed as dissociation constant incubated for 6 to 24 hrs by radioligand binding assay	kd	<0.0001	uM
2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide	2012283: Displacement of [3H]Sch527123 from human CXCR2 assessed as dissociation constant measured every 30 secs for 48 hrs by radioligand binding assay	kd	<0.0001	uM
sodium methylsulfonyl-[(2R)-2-[4-(trifluoromethylsulfonyloxy)phenyl]propanoyl]azanide	1513652: Inhibition of CXCR2 (unknown origin)	ic50	0.0001	uM
3-[[2-(2,2-diethylhydrazinyl)-3,4-dioxocyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide	1528063: Antagonist activity at CXCR2 (unknown origin)	ic50	0.0001	uM
1-(3-tert-butylsulfonyl-4-cyano-2-hydroxyphenyl)-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0002	uM
1-[4-chloro-3-(4-fluorooxan-4-yl)sulfonyl-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0002	uM
1-[4-cyano-2-hydroxy-3-(4,4,4-trifluoro-2-methylbutan-2-yl)sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0002	uM
N-[2-[(2,3-difluorophenyl)methylsulfanyl]-6-[(2R,3S)-3,4-dihydroxybutan-2-yl]oxypyrimidin-4-yl]azetidine-1-sulfonamide	2012282: Binding affinity to NanoLuc fused Snap CXCR2 (unknown origin) expressed in HEK293 cell membrane assessed as inhibition constant using furimazine as substrate incubated with substrate for 5 mins and measured every 15 secs for 60 mins by luminescence based NanoBRET fluorescent binding assay	ki	0.0002	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494745: Displacement of [125I]IL-8 from human recombinant CXCR2 receptor after 60 mins by scintillation counting analysis	ic50	0.0002	uM
1-[4-chloro-2-hydroxy-3-[(1R,3R)-3-hydroxycyclopentyl]sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0003	uM
1-[4-chloro-2-hydroxy-3-[2-(oxetan-3-yl)propan-2-ylsulfonyl]phenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0003	uM
1-[4-chloro-3-(4-ethyloxan-4-yl)sulfonyl-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0003	uM
1-[(1R)-2-chlorocyclopent-2-en-1-yl]-3-[4-chloro-2-hydroxy-3-(4-hydroxy-2-methylbutan-2-yl)sulfonylphenyl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0003	uM
1-(4-chloro-3-cyclobutylsulfonyl-2-hydroxyphenyl)-3-(2-chloro-3-fluorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0003	uM
1-(4-chloro-3-cyclohexylsulfonyl-2-hydroxyphenyl)-3-(2-chloro-3-fluorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0003	uM
1-(4-chloro-3-cyclopentylsulfonyl-2-hydroxyphenyl)-3-(2-chloro-3-fluorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0003	uM
1-[4-chloro-3-(1,1-difluoroethylsulfonyl)-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0004	uM
1-(4-chloro-2-hydroxy-3-propan-2-ylsulfonylphenyl)-3-(2-methylcyclopent-2-en-1-yl)urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0004	uM
1-(2-chloro-3-fluorophenyl)-3-(4-chloro-2-hydroxy-3-propan-2-ylsulfonylphenyl)urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0004	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-[(2-methyl-2-azaspiro[3.3]heptan-6-yl)sulfonyl]phenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0004	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-[(3-methyl-3-azaspiro[5.5]undecan-9-yl)sulfonyl]phenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0004	uM
1-[4-chloro-3-(1-cyclobutylpiperidin-4-yl)sulfonyl-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0004	uM
1-[4-chloro-2-hydroxy-3-[2-(oxan-4-yl)propan-2-ylsulfonyl]phenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0005	uM
1-[4-chloro-2-hydroxy-3-(4-methyloxan-4-yl)sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0005	uM
1-[(1R)-2-chlorocyclopent-2-en-1-yl]-3-[4-chloro-3-(4-fluorooxan-4-yl)sulfonyl-2-hydroxyphenyl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0005	uM
1-[4-chloro-2-hydroxy-3-(1,1,1-trifluoro-2-methylpropan-2-yl)sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0005	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-(1-methylpiperidin-4-yl)sulfonylphenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-[4-chloro-2-hydroxy-3-(oxolan-3-ylsulfonyl)phenyl]-3-(2,3-dichlorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-[(3S)-1-methylpyrrolidin-3-yl]sulfonylphenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-[(4S)-1-methylazepan-4-yl]sulfonylphenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-(4-chloro-3-ethylsulfonyl-2-hydroxyphenyl)-3-(2,3-dichlorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-(piperidine-1-carbonyl)phenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-(3-tert-butylsulfonyl-4-chloro-2-hydroxyphenyl)-3-(2-chloro-3-fluorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0005	uM
1-(4-chloro-2-hydroxy-3-piperazin-1-ylsulfonylphenyl)-3-(2,3-dichlorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0006	uM
1-[4-chloro-3-[1-(2-fluoroethyl)piperidin-4-yl]sulfonyl-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0006	uM
1-(4-chloro-2-hydroxy-3-propan-2-ylsulfonylphenyl)-3-(2,3-dichlorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0006	uM
1-[4-chloro-3-(1-fluoro-2-methylpropan-2-yl)sulfonyl-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0006	uM
3-[[2-[[(1R)-1-(4-butan-2-ylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide	307569: Displacement of [125I]IL8 from human CXCR2 expressed in CHO cells by SPA	ki	0.0006	uM
[4-[(2R)-1-(methanesulfonamido)-1-oxopropan-2-yl]phenyl] trifluoromethanesulfonate	2033688: Antagonist activity at CXCR2 (unknown origin)	ic50	0.0007	uM
1-[4-chloro-3-(3-fluorooxolan-3-yl)sulfonyl-2-hydroxyphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0008	uM
1-[4-chloro-2-hydroxy-3-(4-methylpiperazin-1-yl)sulfonylphenyl]-3-(2,3-dichlorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0008	uM
1-[4-chloro-2-hydroxy-3-(oxan-4-ylsulfonyl)phenyl]-3-(2,3-dichlorophenyl)urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0008	uM
3-[[3,4-dioxo-2-[[(1R)-1-(4-pentan-3-ylfuran-2-yl)propyl]amino]cyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide	307569: Displacement of [125I]IL8 from human CXCR2 expressed in CHO cells by SPA	ki	0.0008	uM
1-(2-chloro-3-fluorophenyl)-3-[4-chloro-2-hydroxy-3-(4-methylpiperazin-1-yl)sulfonylphenyl]urea	1308335: Antagonist activity at human recombinant Gal4-VP16 fused-CXCR2 assessed as inhibition of CXCL1-mediated lactamase reporter gene expression after overnight incubation	ic50	0.0008	uM
1-[4-chloro-2-hydroxy-3-[(3S)-3-methyloxolan-3-yl]sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0010	uM
3-[[2-[[(1R)-1-(4-ethylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide	307569: Displacement of [125I]IL8 from human CXCR2 expressed in CHO cells by SPA	ki	0.0010	uM
3-[[3,4-dioxo-2-[[(1R)-1-(4-propan-2-ylfuran-2-yl)propyl]amino]cyclobuten-1-yl]amino]-2-hydroxy-N,N-dimethylbenzamide	307569: Displacement of [125I]IL8 from human CXCR2 expressed in CHO cells by SPA	ki	0.0010	uM
(2R)-2-[[2-amino-5-[(2,3-difluorophenyl)methylsulfanyl]-[1,3]thiazolo[4,5-d]pyrimidin-7-yl]amino]propan-1-ol	295328: Antagonistic activity against human CXCR2 in neutrophils assessed as blockade of GROalpha stimulated calcium mobilisation by FLIPR	kd	0.0010	uM
1-[4-chloro-2-hydroxy-3-(3-pyrrolidin-1-ylcyclobutyl)sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0010	uM
1-[4-chloro-2-hydroxy-3-[(3R)-3-methyloxolan-3-yl]sulfonylphenyl]-3-[(1R)-2-methylcyclopent-2-en-1-yl]urea	1455186: Antagonist activity at TEV protease cleavage site linked GAL4-VP16-fused recombinant human CXCR2 expressed in cells assessed as inhibition of TEV protease tagged human CXCL1-stimulated beta-arrestin recruitment by CCF4-AM-fluorescence based FRET assay	ic50	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Lipopolysaccharides	affects cotreatment, decreases expression, decreases reaction, increases expression, affects response to substance	5
Benzo(a)pyrene	affects methylation, decreases expression, increases expression	4
Aflatoxin B1	increases methylation, decreases expression, increases expression	4
SB 225002	decreases reaction, affects binding, decreases activity	3
Calcium	affects transport, affects binding, increases activity, increases uptake, increases abundance	3
sodium arsenite	affects expression, affects methylation	2
Estradiol	affects expression, affects cotreatment, decreases expression	2
Nickel	decreases expression, increases expression	2
Nicotine	decreases expression, increases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
lipoteichoic acid	decreases expression	1
ferrous sulfate	decreases expression	1
oleandrin	increases expression	1
1-nitropyrene	decreases expression	1
nicotinamide N-oxide	affects binding, decreases activity	1
S-(1,2-dichlorovinyl)cysteine	decreases expression, affects response to substance, increases expression, affects cotreatment	1
lipoarabinomannan	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
SB 203580	decreases reaction, decreases expression	1
2-aminoethoxydiphenyl borate	increases activity, decreases reaction	1
monomethylarsonous acid	affects localization	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
doramapimod	decreases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
N-(3-(aminosulfonyl)-4-chloro-2-hydroxyphenyl)-N’-(2,3-dichlorophenyl)urea	affects binding, decreases activity	1
reparixin	decreases activity, affects binding	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1

ChEMBL screening assays

272 unique, capped per target: 201 binding, 71 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003796	Binding	Displacement of [125I]IL8 from human CXCR1/2 expressed in CHO cells at 10 uM	Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists. — Bioorg Med Chem Lett
CHEMBL3386571	Functional	Antagonist activity at CXCR1/CXCR2 in human PMNs assessed as inhibition of CXCL8-induced intracellular Ca2+ release by fluorescence based calcium flux assay	Discovery of 2-[5-(4-Fluorophenylcarbamoyl)pyridin-2-ylsulfanylmethyl]phenylboronic Acid (SX-517): Noncompetitive Boronic Acid Antagonist of CXCR1 and CXCR2. — J Med Chem

Cellosaurus cell lines

9 cell lines: 3 cancer cell line, 3 transformed cell line, 3 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1AD	Abcam THP-1 CXCR2 KO	Cancer cell line	Male
CVCL_D9CR	Ubigene HEK293 CXCR2 KO	Transformed cell line	Female
CVCL_F1WI	293-IL-8RB	Transformed cell line	Female
CVCL_KT03	CHO-K1 (+Galpha16) AequoScreen CXCR2	Spontaneously immortalized cell line	Female
CVCL_KV01	cAMP Hunter CHO-K1 CXCR2 Gi	Spontaneously immortalized cell line	Female
CVCL_KW78	PathHunter CHO-K1 CXCR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ41	PathHunter HEK 293 CXCR2 beta-arrestin	Transformed cell line	Female
CVCL_LA13	PathHunter U2OS CXCR2 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZK10	Tango CXCR2-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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