CXCR6

Summary

CXCR6 (C-X-C motif chemokine receptor 6, HGNC:16647) is a protein-coding gene on chromosome 3p21.31, encoding C-X-C chemokine receptor type 6 (O00574). Receptor for the C-X-C chemokine CXCL16.

The protein encoded by this gene is a G protein-coupled receptor with seven transmembrane domains that belongs to the CXC chemokine receptor family. This family also includes CXCR1, CXCR2, CXCR3, CXCR4, CXCR5, and CXCR7. This gene, which maps to the chemokine receptor gene cluster, is expressed in several T lymphocyte subsets and bone marrow stromal cells. The encoded protein and its exclusive ligand, chemokine ligand 16 (CCL16), are part of a signalling pathway that regulates T lymphocyte migration to various peripheral tissues (the liver, spleen red pulp, intestine, lungs, and skin) and promotes cell-cell interaction with dendritic cells and fibroblastic reticular cells. CXCR6/CCL16 also controls the localization of resident memory T lymphocytes to different compartments of the lung and maintains airway resident memory T lymphocytes, which are an important first line of defense against respiratory pathogens. The encoded protein serves as an entry coreceptor used by HIV-1 and SIV to enter target cells, in conjunction with CD4.

Source: NCBI Gene 10663 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 33 total
• Druggable target: yes
• MANE Select transcript: NM_006564

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16647
Approved symbol	CXCR6
Name	C-X-C motif chemokine receptor 6
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	TYMSTR, STRL33, BONZO, CD186
Ensembl gene	ENSG00000172215
Ensembl biotype	protein_coding
OMIM	605163
Entrez	10663

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000304552, ENST00000438735, ENST00000457814, ENST00000458629, ENST00000965370

RefSeq mRNA: 4 — MANE Select: NM_006564 NM_001386435, NM_001386436, NM_001386437, NM_006564

CCDS: CCDS2735

Canonical transcript exons

ENST00000304552 — 2 exons

Exon	Start	End
ENSE00001174257	45946461	45948351
ENSE00001523343	45943464	45943540

Expression profiles

Bgee: expression breadth ubiquitous, 164 present calls, max score 81.80.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.7713 / max 304.7808, expressed in 140 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36402	1.2642	107
36404	0.2395	62
36403	0.1481	41
36399	0.0710	11
36401	0.0251	7
36400	0.0233	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	81.80	gold quality
spleen	UBERON:0002106	80.39	gold quality
lymph node	UBERON:0000029	78.01	gold quality
amniotic fluid	UBERON:0000173	77.68	gold quality
gall bladder	UBERON:0002110	77.06	gold quality
vermiform appendix	UBERON:0001154	75.15	gold quality
blood	UBERON:0000178	74.81	gold quality
tonsil	UBERON:0002372	72.47	gold quality
mucosa of transverse colon	UBERON:0004991	72.27	gold quality
granulocyte	CL:0000094	72.22	gold quality
colonic epithelium	UBERON:0000397	72.19	gold quality
rectum	UBERON:0001052	72.09	gold quality
small intestine Peyer’s patch	UBERON:0003454	72.05	gold quality
nasal cavity epithelium	UBERON:0005384	71.95	silver quality
placenta	UBERON:0001987	71.90	gold quality
endothelial cell	CL:0000115	71.83	silver quality
palpebral conjunctiva	UBERON:0001812	71.62	gold quality
small intestine	UBERON:0002108	71.28	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	71.22	gold quality
squamous epithelium	UBERON:0006914	71.18	silver quality
tongue squamous epithelium	UBERON:0006919	70.53	gold quality
caecum	UBERON:0001153	70.13	gold quality
esophagus squamous epithelium	UBERON:0006920	69.63	silver quality
muscle of leg	UBERON:0001383	69.54	gold quality
gastrocnemius	UBERON:0001388	69.14	gold quality
superficial temporal artery	UBERON:0001614	68.93	silver quality
decidua	UBERON:0002450	68.79	silver quality
body of stomach	UBERON:0001161	68.55	gold quality
ileal mucosa	UBERON:0000331	68.34	silver quality
epithelium of nasopharynx	UBERON:0001951	68.23	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-CURD-95	yes	625.39
E-MTAB-8410	yes	14.48
E-ANND-3	yes	9.11

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): STAT3

Literature-anchored findings (GeneRIF, showing 40)

• Chemokine receptor expression on MBP-reactive T cells: CXCR6 is a marker of IFNgamma-producing effector cells. (PMID:12044980)
• CCR1, CCR6, and CXCR6 are preferentially expressed by the low cytokine-producing CD8 and CD4(-)CD8(-) subsets of natural killer T-cells. (PMID:12070001)
• There is an association between CXCR6 genotype and progression from Pneumocystis carinii pneumonia to death in African-Americans with AIDS. (PMID:12761559)
• CXCR6 expression is down-regulated, independent of CCR5 or CD69 expression and of cytokine induction, by T cell activation signals that involve predominantly the Ca(2+)-dependent calcineurin pathway. (PMID:12914753)
• The chemokine domain of SR-PSOX/CXCL16 mediated the adhesion of CXCR6-expressing cells, which was not impaired by treatment with pertussis toxin, and was up-regulated by treatment of SR-PSOX/CXCL16-expressing cells with a metalloprotease inhibitor. (PMID:14634054)
• HIV-2 isolates from aviremic and viremic individuals commonly use as coreceptors CCR5, GPR15, and CXCR6 (PMID:15650194)
• Immunohistochemistry revealed CXCR6 protein predominantly localised in normal colorectal epithelial cells and some scattered stromal cells. No or weak expression was found in cancerous tissue. (PMID:15736401)
• chemokine receptor CXCR6 was overexpressed in Th1 and Tc1 T lymphocytes compared with peripheral blood lymphocytes in Graves disease (PMID:15817921)
• CXCR6 was expressed more frequently on synovial T cells than in peripheral blood (PMID:16200580)
• LPS upregulates CXCR6 mRNA, protein, & surface expression in human aortic smooth muscle cells. Inhibition of TLR4 blocked LPS-mediated CXCR6 expression. LPS stimulated both AP-1 (c-Fos, c-Jun) and NF-kappaB (p50 and p65) activation. (PMID:16870145)
• T cells expressing CCR6, CXCR3, and CXCR6 act coordinately with respective ligands and Th1 inflammatory cytokines in the alveolitic/granuloma phases of the disease. (PMID:17615381)
• Data show that CC chemokine receptor 5 and CXC chemokine receptor 6 expression by lung CD8+ cells correlates with chronic obstructive pulmonary disease severity. (PMID:17640964)
• HIV-1 infected patients with initial viral load suppression due to HAART showed a faster virologic failure in the presence of the CXCR6-3K allele (PMID:17725420)
• Hyperhomocysteinemia up-regulates CXCL16 leading to increased recruitment of CXCR6(+) lymphocytes and scavenging of modified lipids via a potential involvement of a PPAR-gamma-dependent mechanism (PMID:18194461)
• CXCL16 interaction with CXCR6 on T cells, gammadelta T cells, and monocytes leads to forming a specialized immune milieu at the maternofetal interface. (PMID:18250446)
• Expression of the CXCL16-CXCR6-system in human schwannomas of different localization and in malignant peripheral nerve sheath tumors. (PMID:18293410)
• besides CXCL12/CXCR4, CXCL16/CXCR6 might be another important factor involved in PCa bone metastasis. (PMID:18452560)
• it is proposed that CXCR6 may play an important role in the retention of T cells within the lung (PMID:18656707)
• CXCR6 and CXCR3 act coordinately with respective ligands and are involved in the pathophysiology of Juvenile Idiopathic Arthritis-associated inflammatory processes. (PMID:18760678)
• Chemokine C-X-C motif receptor 6 contributes to cell migration during hypoxia. (PMID:19231068)
• data suggest that CXCL16 and CXCR6 may mark cancers arising in an inflammatory milieu and mediate pro-tumorigenic effects of inflammation through effects on cancer cell growth and by inducing the migration and proliferation of tumor-associated leukocytes (PMID:19690611)
• CXCR6 protein was detected in all clinical prostate cancer samples. Both PC3 and LNCap cells expressed CXCR6 mRNA and protein. (PMID:20646641)
• The statistical significance, the replication, and the magnitude of the association demonstrate that CXCR6 is likely involved in the molecular etiology of AIDS and, in particular, in long-term nonprogression. (PMID:20704485)
• CXCR6 has a role in aggressive tumor phenotype in melanoma (PMID:21203549)
• The CXCL16 A181V mutation selectively inhibits monocyte adhesion to CXCR6 but is not associated with human coronary heart disease. (PMID:21233446)
• CXCL16 and CXCR6 are elevated in Systemic sclerosis (SSc) serum and on SSc dermal Endothelial cells, respectively (PMID:21303517)
• High CXCL16/CXCR6 expression may be related to aggressive cancer behavior, and high CXCL16 expression to bone metastases. (PMID:21468586)
• The expressions of CXCL12/CXCR4 and CXCL16/CXCR6 were significantly higher in epithelial ovarian carcinomas than in normal epithelial ovarian tissues or benign epithelial ovarian tumors. Expression of CXCR6 was related to lymph node metastasis. (PMID:21527066)
• CXCL16 and CXCR6 might be involved in the pathophysiology of endometriosis through regulation of the inflammatory response. (PMID:21773780)
• The data supported a role for CCR5, CXCR3, and CXCR6 in the selective recruitment of T cells into renal cell carcinoma tissue and, together with CCR6, in the recruitment of regulatory T cells. (PMID:22079021)
• The results indicated that CXCL16-CXCR6 interactions mediate homing of CD8+ T cells into human skin, and thereby contribute to psoriasis pathogenesis. (PMID:22113484)
• the present review proposes and discusses the possibility to modulate tumor self renewal affecting asymmetric/symmetric cell division targeting specific factors such as CXCR6. (PMID:22678828)
• CXCR6 was found to be abundantly expressed in human meningioma samples of different malignant grades. (PMID:23229614)
• Data suggest that expression of CXCR6 in T-cells and natural killer cells is up-regulated in subjects with metabolic syndrome and correlates with severity of carotid atherosclerosis (i.e., intima-media thickness and plaque index). (PMID:23398954)
• CXCL16 is highly expressed by glial tumor and stroma cells whereas CXCR6 defines a subset of cells with stem cell character. (PMID:23628207)
• CXCL16/CXCR6 interaction may play an important role in modifying the response of pDCs to environmental danger signals (PMID:24302814)
• Our results suggest that the CXCL16/CXCR6 axis appears to be important in the progression of Ewing sarcoma family tumor (PMID:24507753)
• high expression of CXCR6 is positively associated with distant invasion of human hepatocellular carcinoma (HCC) patients. (PMID:25572735)
• Authors present evidence that chemokine receptor CXCR6 and its only natural ligand, CXCL16, are significantly expressed by non-small cell lung cancer (NSCLC) and are involved in the pathobiology of lung cancer. (PMID:25888629)
• The expression level of CXCR6 was increased in gastric cancer. (PMID:25921630)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cxcr6	ENSMUSG00000048521
rattus_norvegicus	Cxcr6	ENSRNOG00000089617

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), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-X-C chemokine receptor type 6 — O00574 (reviewed: O00574)

Alternative names: CDw186, G-protein coupled receptor STRL33, G-protein coupled receptor bonzo

All UniProt accessions (2): A0N0N3, O00574

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the C-X-C chemokine CXCL16. Used as a coreceptor by SIVs and by strains of HIV-2 and m-tropic HIV-1.

Subcellular location. Cell membrane.

Tissue specificity. Expressed in lymphoid tissues and activated T cells.

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

RefSeq proteins (4): NP_001373364, NP_001373365, NP_001373366, NP_006555* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR002235	Chemokine_CXCR6	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (20 total): topological domain 8, transmembrane region 7, sequence variant 2, chain 1, glycosylation site 1, disulfide bond 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00574-F1	82.16	0.51

Functional residue map

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

Disulfide bonds (1): 102–180

Glycosylation sites (1): 16

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 244 (showing top): GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_64, GOCC_CELL_SURFACE, MODULE_128, RIZKI_TUMOR_INVASIVENESS_3D_DN, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MODULE_289, MODULE_171, GOBP_VIRAL_GENOME_REPLICATION, MODULE_123, GOBP_VIRAL_LIFE_CYCLE, SHIN_B_CELL_LYMPHOMA_CLUSTER_3

GO Biological Process (10): inflammatory response (GO:0006954), immune response (GO:0006955), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), viral genome replication (GO:0019079), calcium-mediated signaling (GO:0019722), cell chemotaxis (GO:0060326), chemotaxis (GO:0006935), signal transduction (GO:0007165), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (6): G protein-coupled receptor activity (GO:0004930), coreceptor activity (GO:0015026), C-C chemokine receptor activity (GO:0016493), C-X-C chemokine receptor activity (GO:0016494), C-C chemokine binding (GO:0019957), chemokine receptor activity (GO:0004950)

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	2
chemokine receptor activity	2
chemokine binding	2
defense response	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
signal transduction	1
regulation of biological quality	1
viral process	1
viral life cycle	1
intracellular signaling cassette	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
response to chemical	1
taxis	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
transmembrane signaling receptor activity	1
signaling receptor activity	1
C-C chemokine binding	1
C-X-C chemokine binding	1
G protein-coupled chemoattractant receptor activity	1
cytokine receptor activity	1
chemokine-mediated signaling pathway	1
membrane	1
cell periphery	1
plasma membrane	1
cell surface	1
side of membrane	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1700 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCR6	CXCL16	Q9H2A7	999
CXCR6	CXCL9	Q07325	944
CXCR6	CXCL12	P48061	940
CXCR6	FYCO1	Q9BQS8	930
CXCR6	CXCL10	P02778	911
CXCR6	CCL20	P78556	878
CXCR6	CCL5	P13501	849
CXCR6	CX3CL1	P78423	835
CXCR6	CCR5	P51681	829
CXCR6	CCL3	P10147	817
CXCR6	CXCR3	P49682	777
CXCR6	CD69	Q07108	769
CXCR6	CD8A	P01732	768
CXCR6	GZMA	P12544	741
CXCR6	CCR7	P32248	717

IntAct

5 interactions, top by confidence:

A	B	Type	Score
RAMP1	CXCR6	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CXCR6	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CXCR6	psi-mi:“MI:0915”(physical association)	0.400
CXCR6	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
CXCR6	RAMP3	psi-mi:“MI:0915”(physical association)	0.400

ESM2 similar proteins: A6QNL7, O00574, O18793, O18983, O19024, O54814, O55193, O62743, O97879, O97880, O97882, P32246, P35343, P35407, P35411, P49238, P51675, P51677, P51678, P51683, P56440, P56482, P56483, P56492, P60574, P61757, Q1ZY22, Q2HJ17, Q2KTE1, Q2Y2P0, Q5ECR9, Q64H34, Q6WN98, Q8HZT9, Q95NC2, Q95NC4, Q95NC6, Q95NC7, Q95NC9, Q9BDS6

Diamond homologs: A6QNL7, O00421, O00574, O00590, O08556, O09027, O18793, O35210, O35457, O54814, O55193, O62743, O77590, O97665, O97878, O97879, O97880, O97881, O97882, O97883, O97962, O97975, P25095, P25104, P29089, P29754, P29755, P30555, P32246, P35411, P41597, P43240, P46094, P49238, P51675, P51676, P51677, P51678, P51679, P51680

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
hsa-miR-361-5p	“down-regulates quantity by repression”	CXCR6	“post transcriptional regulation”
hsa-miR-361-5p	“down-regulates quantity by destabilization”	CXCR6	“post transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

258 predictions. Top by Δscore:

Variant	Effect	Δscore
3:45946455:TCACA:T	acceptor_loss	0.9900
3:45946456:CACA:C	acceptor_loss	0.9900
3:45946457:ACAG:A	acceptor_loss	0.9900
3:45946458:CA:C	acceptor_loss	0.9900
3:45946459:A:AT	acceptor_loss	0.9900
3:45946460:G:GC	acceptor_loss	0.9900
3:45946460:GGT:G	acceptor_gain	0.9700
3:45943305:G:GT	donor_gain	0.9500
3:45944813:G:T	donor_gain	0.9500
3:45946459:A:AG	acceptor_gain	0.9400
3:45946460:G:GG	acceptor_gain	0.9400
3:45943317:ATC:A	donor_gain	0.9200
3:45944813:G:GT	donor_gain	0.8800
3:45944789:C:T	donor_gain	0.8600
3:45941060:C:G	donor_gain	0.8400
3:45941343:GCAG:G	donor_gain	0.7900
3:45943444:G:T	acceptor_gain	0.7800
3:45941291:TCTTC:T	donor_gain	0.7400
3:45946457:A:AG	acceptor_gain	0.7200
3:45945420:TTAC:T	donor_gain	0.7100
3:45946459:AG:A	acceptor_gain	0.7100
3:45946460:GG:G	acceptor_gain	0.7100
3:45941293:TTCAG:T	donor_loss	0.7000
3:45941294:TCAG:T	donor_loss	0.7000
3:45941295:CAG:C	donor_loss	0.7000
3:45941296:AG:A	donor_loss	0.7000
3:45941298:G:GA	donor_loss	0.7000
3:45943416:A:AG	acceptor_gain	0.7000
3:45943417:G:GG	acceptor_gain	0.7000
3:45941300:A:C	donor_loss	0.6900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000801105 (3:45943382 T>C,G), RS1001167944 (3:45940976 T>C), RS1001450996 (3:45940582 C>A,G), RS1001481492 (3:45940365 G>A), RS1001494356 (3:45943894 A>G), RS1002363823 (3:45943026 G>A,C), RS1002950390 (3:45946191 T>C), RS1003272454 (3:45948227 A>G), RS1003491524 (3:45943717 A>C), RS1003500236 (3:45941052 C>G), RS1003772492 (3:45941322 G>C), RS1004217691 (3:45945398 G>A), RS1005222941 (3:45947354 C>T), RS1005250297 (3:45940227 G>A), RS1005279959 (3:45939792 C>G)

Disease associations

OMIM: gene MIM:605163 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST90000255_22	Severe COVID-19 infection with respiratory failure (analysis I)	1.000000e-10
GCST90000256_1	Severe COVID-19 infection with respiratory failure (analysis II)	9.000000e-12

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5994 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: gpcr — Chemokine receptors

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
CXCL16	Full agonist	9.0	pKd

ChEMBL bioactivities

67 potent at pChembl≥5 of 89 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	1.995	nM	CHEMBL3979652
7.40	IC50	40	nM	CHEMBL4637126
7.40	IC50	39.81	nM	CHEMBL4637126
7.10	IC50	80	nM	CHEMBL4638895
6.96	IC50	110	nM	CHEMBL4632425
6.92	IC50	120	nM	CHEMBL4647701
6.89	IC50	130	nM	CHEMBL4646569
6.89	IC50	130	nM	CHEMBL4646120
6.85	IC50	140	nM	CHEMBL4645971
6.80	IC50	160	nM	CHEMBL4640388
6.80	IC50	160	nM	CHEMBL4648997
6.77	IC50	170	nM	CHEMBL4641681
6.60	IC50	250	nM	CHEMBL4639692
6.58	IC50	260	nM	CHEMBL4638493
6.57	IC50	270	nM	CHEMBL4640319
6.52	IC50	300	nM	CHEMBL4642230
6.51	IC50	310	nM	CHEMBL4647206
6.46	IC50	350	nM	CHEMBL4645763
6.46	IC50	350	nM	CHEMBL4649351
6.39	IC50	410	nM	CHEMBL4635707
6.39	IC50	410	nM	CHEMBL4647701
6.30	IC50	500	nM	CHEMBL4637126
6.21	IC50	620	nM	CHEMBL4644133
6.21	IC50	610	nM	CHEMBL4639114
6.19	IC50	640	nM	CHEMBL4639996
6.16	IC50	700	nM	CHEMBL4646569
6.10	IC50	790	nM	CHEMBL4640657
6.08	IC50	840	nM	CHEMBL4640101
6.05	IC50	900	nM	CHEMBL4640388
6.05	IC50	900	nM	CHEMBL4648997
6.05	IC50	900	nM	CHEMBL4633183
6.05	IC50	900	nM	CHEMBL4646120
6.03	IC50	930	nM	CHEMBL4632989
6.00	IC50	1000	nM	CHEMBL4638895
5.89	IC50	1300	nM	CHEMBL4647206
5.85	IC50	1400	nM	CHEMBL4645971
5.82	IC50	1500	nM	CHEMBL4638791
5.80	IC50	1600	nM	CHEMBL4645361
5.75	IC50	1800	nM	CHEMBL4648121
5.75	IC50	1800	nM	CHEMBL4649351
5.72	IC50	1900	nM	CHEMBL4632425
5.68	IC50	2100	nM	CHEMBL4646463
5.68	IC50	2100	nM	CHEMBL4637126
5.51	IC50	3100	nM	CHEMBL4636339
5.50	IC50	3200	nM	CHEMBL4641681
5.47	IC50	3400	nM	CHEMBL4637473
5.42	IC50	3800	nM	CHEMBL4645763
5.37	IC50	4300	nM	CHEMBL4635707
5.32	IC50	4800	nM	CHEMBL4639692
5.28	IC50	5300	nM	CHEMBL4644085

PubChem BioAssay actives

67 with measured affinity, of 264 total; 42 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
2-hydroxy-N,N-dimethyl-3-[[2-[[(5-methylfuran-2-yl)-(2-methyloxolan-2-yl)methyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide	1953246: Antagonist activity at CXCR6 (unknown origin)	ic50	0.0020	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-[[4-(trifluoromethyl)-1,3-benzothiazol-2-yl]methyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.0398	uM
N-[(1S,5R)-9-[(4-bromo-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.0800	uM
N-[(1S,5R)-9-[(4-fluoro-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1100	uM
N-[(1R,5S)-9-[2-(2,3-dichloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1200	uM
N-[(1S,5R)-9-[(4-chloro-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1300	uM
N-[(1R,5S)-9-[2-(2,5-dichloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1300	uM
N-[(1S,5R)-9-[2-(2-chloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1400	uM
N-[(1R,5S)-9-[2-(2-bromoanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1600	uM
N-[(1R,5S)-9-[2-(2,4-dichloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1600	uM
N-[(1S,5R)-9-[(5-chloro-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.1700	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-[(4-methyl-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.2500	uM
N-[(1S,5R)-9-[(7-chloro-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.2600	uM
N-[(1S,5R)-9-[(6-chloro-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.2700	uM
N-[(1S,5R)-9-(1,3-benzothiazol-2-ylmethyl)-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.3000	uM
N-[(1R,5S)-9-[2-(3,5-dichloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.3100	uM
N-[(1R,5S)-9-[2-(3-bromoanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.3500	uM
N-[(1R,5S)-9-[2-(3,4-dichloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.3500	uM
N-[(1R,5S)-9-[2-(3-chloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.4100	uM
N-[(1S,5R)-9-[2-(2,5-dimethylanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.6100	uM
N-[(1R,5S)-9-[2-(2-fluoroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.6200	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-[2-oxo-2-[2-(trifluoromethyl)anilino]ethyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.6400	uM
3,4,5-trimethoxy-N-[(1R,5S)-9-[2-(2-methylanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.7900	uM
N-[(1R,5S)-9-[2-(3-fluoroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.8400	uM
N-[(1S,5R)-9-(1-benzothiophen-2-ylmethyl)-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.9000	uM
N-[(1R,5S)-9-[2-(2-cyanoanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	0.9300	uM
N-[(1R,5S)-9-[2-(4-chloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	1.5000	uM
ethyl 2-[[2-[(1R,5S)-3-[(3,4,5-trimethoxybenzoyl)amino]-9-azabicyclo[3.3.1]nonan-9-yl]acetyl]amino]benzoate	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	1.6000	uM
3,4,5-trimethoxy-N-[(1R,5S)-9-[2-(3-methylanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	1.8000	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-[2-(2-methoxyanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	2.1000	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-[(4-methoxy-1,3-benzothiazol-2-yl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	3.1000	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-(naphthalen-2-ylmethyl)-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	3.4000	uM
N-[(1R,5S)-9-[2-(4-chloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-1,3-benzodioxole-5-carboxamide	1651022: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay	ic50	5.3000	uM
3,4,5-trimethoxy-N-[(1S,5R)-9-[2-(3-methoxyanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	5.8000	uM
N-[(1R,5S)-9-[2-(4-fluoroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	5.8000	uM
N-[(1S,5R)-9-(2-anilino-2-oxoethyl)-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	5.8000	uM
N-[(1S,5R)-9-[2-(4-chloroanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]-4-methoxybenzamide	1651022: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of forskolin-induced cAMP accumulation by DiscoveRx cell based assay	ic50	5.9000	uM
3,4,5-trimethoxy-N-[(1R,5S)-9-(quinolin-2-ylmethyl)-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	6.7000	uM
N-[(1S,5R)-9-[(2-chlorophenyl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	6.8000	uM
N-[(1S,5R)-9-(1,3-benzoxazol-2-ylmethyl)-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	6.9000	uM
N-[(1S,5R)-9-[(3-chlorophenyl)methyl]-9-azabicyclo[3.3.1]nonan-3-yl]-3,4,5-trimethoxybenzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	9.5000	uM
3,4,5-trimethoxy-N-[(1R,5S)-9-[2-(4-methylanilino)-2-oxoethyl]-9-azabicyclo[3.3.1]nonan-3-yl]benzamide	1651020: Antagonist activity at Prolink-tagged human CXCR6 receptor assessed as inhibition of CXCL16-induced beta-arrestin recruitment by DiscoveRx cell based assay	ic50	9.5000	uM

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Nickel	increases expression	2
triphenyl phosphate	affects expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
Aripiprazole	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Benzene	increases expression	1
Methotrexate	decreases expression	1
Ozone	affects cotreatment, increases expression	1
Testosterone	decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Paclitaxel	decreases response to substance	1
Antirheumatic Agents	decreases expression	1
beta-Naphthoflavone	decreases expression	1
Endocannabinoids	increases activity, affects binding, decreases reaction	1

ChEMBL screening assays

22 unique, capped per target: 16 binding, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1952673	Binding	Activity at human CXCR6 receptor at 10 uM	γ-Carbolines: a novel class of cannabinoid agonists with high aqueous solubility and restricted CNS penetration. — Bioorg Med Chem Lett
CHEMBL2328612	Functional	Antagonist activity at CXCR6 (unknown origin) assessed as inhibition of calcium flux at 10 uM	1-(4-Phenylpiperazin-1-yl)-2-(1H-pyrazol-1-yl)ethanones as novel CCR1 antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

11 cell lines: 6 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line, 1 undefined cell line type

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

Cellosaurus	Name	Category	Sex
CVCL_1E13	3T3.T4.Bonzo	Transformed cell line	Male
CVCL_B8EF	Abcam HCT 116 CXCR6 KO	Cancer cell line	Male
CVCL_B9GN	Abcam A-549 CXCR6 KO	Cancer cell line	Male
CVCL_C4TU	Chem-5 CXCR6	Undefined cell line type
CVCL_D2ES	Abcam MCF-7 CXCR6 KO	Cancer cell line	Female
CVCL_KV05	cAMP Hunter CHO-K1 CXCR6 Gi	Spontaneously immortalized cell line	Female
CVCL_KW81	PathHunter CHO-K1 CXCR6 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ42	PathHunter HEK 293 CXCR6 beta-arrestin	Transformed cell line	Female
CVCL_LA17	PathHunter U2OS CXCR6 Total GPCR Internalization	Cancer cell line	Female
CVCL_S493	GHOST(3).CXCR6	Cancer cell line	Female

Clinical trials (associated diseases)

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