CXCR3

Summary

CXCR3 (C-X-C motif chemokine receptor 3, HGNC:4540) is a protein-coding gene on chromosome Xq13.1, encoding C-X-C chemokine receptor type 3 (P49682). Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway.

This gene encodes a G protein-coupled receptor with selectivity for three chemokines, termed CXCL9/Mig (monokine induced by interferon-g), CXCL10/IP10 (interferon-g-inducible 10 kDa protein) and CXCL11/I-TAC (interferon-inducible T cell a-chemoattractant). Binding of chemokines to this protein induces cellular responses that are involved in leukocyte traffic, most notably integrin activation, cytoskeletal changes and chemotactic migration. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. One of the isoforms (CXCR3-B) shows high affinity binding to chemokine, CXCL4/PF4 (PMID:12782716).

Source: NCBI Gene 2833 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 46 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001504

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4540
Approved symbol	CXCR3
Name	C-X-C motif chemokine receptor 3
Location	Xq13.1
Locus type	gene with protein product
Status	Approved
Aliases	CKR-L2, CMKAR3, IP10-R, MigR, CD183
Ensembl gene	ENSG00000186810
Ensembl biotype	protein_coding
OMIM	300574
Entrez	2833

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000373691, ENST00000373693

RefSeq mRNA: 2 — MANE Select: NM_001504 NM_001142797, NM_001504

CCDS: CCDS14416, CCDS48135

Canonical transcript exons

ENST00000373693 — 2 exons

Exon	Start	End
ENSE00001461244	71615919	71617459
ENSE00001817013	71618438	71618511

Expression profiles

Bgee: expression breadth ubiquitous, 126 present calls, max score 91.12.

FANTOM5 (CAGE): breadth broad, TPM avg 3.5106 / max 336.1751, expressed in 225 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
199561	3.2756	220
199562	0.2196	71
199560	0.0154	7

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	91.12	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.85	silver quality
lymph node	UBERON:0000029	80.32	gold quality
blood	UBERON:0000178	76.32	gold quality
cervix squamous epithelium	UBERON:0006922	75.51	gold quality
spleen	UBERON:0002106	74.15	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	74.12	gold quality
inferior olivary complex	UBERON:0002127	73.96	gold quality
nasal cavity epithelium	UBERON:0005384	72.99	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	72.84	gold quality
vena cava	UBERON:0004087	71.90	gold quality
vermiform appendix	UBERON:0001154	71.54	gold quality
caecum	UBERON:0001153	71.46	gold quality
triceps brachii	UBERON:0001509	71.44	gold quality
cervix epithelium	UBERON:0004801	70.41	gold quality
mucosa of transverse colon	UBERON:0004991	70.23	gold quality
body of tongue	UBERON:0011876	69.31	gold quality
biceps brachii	UBERON:0001507	69.16	gold quality
bone marrow	UBERON:0002371	69.09	gold quality
lateral nuclear group of thalamus	UBERON:0002736	69.01	gold quality
duodenum	UBERON:0002114	68.98	gold quality
cartilage tissue	UBERON:0002418	68.73	gold quality
gluteal muscle	UBERON:0002000	68.46	gold quality
small intestine Peyer’s patch	UBERON:0003454	68.45	gold quality
medulla oblongata	UBERON:0001896	68.40	gold quality
tongue squamous epithelium	UBERON:0006919	68.40	gold quality
pharyngeal mucosa	UBERON:0000355	68.31	gold quality
substantia nigra pars compacta	UBERON:0001965	68.19	gold quality
cerebellar vermis	UBERON:0004720	68.13	gold quality
olfactory bulb	UBERON:0002264	68.12	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 6.

Experiment	Marker?	Max mean expression
E-HCAD-1	yes	20.81
E-MTAB-8498	yes	13.19
E-CURD-122	yes	12.68
E-CURD-120	yes	10.49
E-CURD-46	yes	9.07
E-CURD-112	yes	4.44
E-ANND-3	no	2.78

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HAND2, TBX21

miRNA regulators (miRDB)

31 targeting CXCR3, 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-4283	100.00	66.42	2097
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4487	99.96	64.58	1252
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-4663	99.62	65.33	957
HSA-MIR-1290	99.59	69.90	2079
HSA-MIR-6165	99.44	67.12	1389
HSA-MIR-1276	99.36	68.18	1642
HSA-MIR-6770-5P	98.97	66.76	1853
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-6810-5P	98.29	66.21	975
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-4749-5P	92.16	62.26	179

Literature-anchored findings (GeneRIF, showing 40)

• chemokine/CXCR3 activity (PMID:11559369)
• downregulation following T cell-endothelial cell contact (PMID:11739530)
• Graves’ disease is associated with an altered CXCR3 expression in thyroid-derived compared to peripheral blood t lymphocytes (PMID:11966764)
• Expression of CXCR3 on CD4+ and CD8+ T cells was significantly reduced after 3 months of interferon beta-1a treatment in multiple sclerosis. (PMID:11990865)
• These findings suggest that the CXCR3/CXCL10 axis may be involved in the T cell recruitment that occurs in peripheral airways of smokers with COPD and that these T cells may have a type-1 profile. (PMID:12016104)
• Most Natural killer t-cells express receptors for extralymphoid tissue or inflammation-related chemokines (CCR2, CCR5, and CXCR3), while few NKT cells express lymphoid tissue-homing chemokine receptors (CCR7 and CXCR5). (PMID:12070001)
• Expression of CXCR3 ligands (MIG, IP-10, and ITAC) in the bronchoalveolar lavage fluid of transplantation recipients is associated with persistent recruitment of mononuclear cells, a pivotal event in the pathogenesis of bronchiolitis obliterans syndrome. (PMID:12097412)
• Gene expression is predictive for the individual response of children with chronic allograft nephropathy to mycophenolate mofetil. (PMID:12270371)
• Significant increase in surface CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients. (PMID:12356205)
• migration of murine and human IFN-producing cells to CXCR3 ligands in vitro requires engagement of CXCR4 by CXCL12 (PMID:12444109)
• Activation of the CXCR3 receptor in proximal tubular cells might disturb natriuresis during inflammatory and ischemic kidney disease via early growth response gene-1-mediated imbalance of reactive oxygen species. (PMID:12517959)
• CXCR3-Mig-coexpressing lymphoma cells were abundant in high MALT of the stomach and thyroid, but rare in other subtypes (PMID:12688353)
• CXCR3-targeting chemokines control T-cell migration via PTX-sensitive, phospholipase C pathways and phosphatidylinositol kinases other than class I PI3Kgamma. (PMID:12750173)
• alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth (PMID:12782716)
• Data suggest that in oral lichen planus, the presence of CCL5 and CXCL10 in the cytolytic granules of tissue-infiltrating CD8(+)T cells expressing CCR5 and CXCR3 reveals a potential self-recruiting mechanism involving activated effector cytotoxic T cells (PMID:12819030)
• eosinophil responses mediated by chemokines acting at CCR3 may be regulated by two distinct mechanisms: the antagonistic effects of CXCR3 ligands and the sequestration of CCL11 by CXCR3-expressing cells (PMID:12884299)
• Targenic of cxcr3 and/or ICOS may have clinical application in the prevention and treatment of chronic allograft nephropathy. (PMID:12919091)
• Ligands control plasmacytoid dendritic cell responsiveness to the constitutive chemokine (SDF-1)/CXCL12. (PMID:12953097)
• In vitro chemotaxis induced by this chemokine is not necessarily predictive of its in vivo lymphocyte-recruiting activity. (PMID:12960247)
• CXCR3 functions broadly–on recently activated as well as fully differentiated CD4+ T cells and on cells that participate in the germinal center reaction as well as on those that infiltrate peripheral inflammatory sites. (PMID:12960302)
• In restinosis, increased plasma concentrations of IP10 were accompanied by a compensatory decrease in the CXCR3 expression on lymphocytes, but not monocytes, suggesting that a high plasma concentration of IP10 strongly induces monocytes signaling. (PMID:14578618)
• Data demonstrate a significant age-dependent difference in the response of osteoblasts to CXCR3 and CXCR5 activation. (PMID:14618028)
• CXCR3-ligation preferentially augments ongoing Th1 over Th2 responses and suggest that reduced capacity of allergic individuals to respond to CXCR3 ligands promotes the maintenance of human allergic disorders (PMID:14657006)
• interstitial CXCR3 may play an important role during progressive loss of renal function (PMID:14742268)
• Mig and IP-10 may be involved in the recruitment of natural killer cells or other phenomena in the human endometrium. (PMID:15126579)
• Intracellular domains of CXCR3 mediate CXCL9, CXCL10, and CXCL11 function (PMID:15150261)
• autocrine activation of CXCR3 expressed by epithelial cells may contribute to airway inflammation and remodeling in obstructive lung disease by regulating cell migration. (PMID:15155273)
• plays an important role in lymphocyte trafficking to CSF during HIV-1 infection (PMID:15181567)
• CXCR3-deficient mice demonstrated increased mortality with progressive interstitial fibrosis, and a reduced early burst of IFN-g, upon injury. CXCR3 deficiency results a deficiency in lung NK cells. (PMID:15254596)
• The CXCR3 ligands IP-10/CXCL10 & Mig/CXCL9 revealed a proproliferative effect but did not influence apoptosis of mesangial cells, suggesting involvement in processes involved in renal inflammation, regeneration and glomerular homeostasis. (PMID:15265234)
• CXCR3 and CCR4 were heterogeneously expressed in peripheral T-cell lymphomas. (PMID:15328188)
• CXCR3 is the principal inflammatory chemokine receptor involved in Behcet’s disease (PMID:15501397)
• A splice variant of CXCR3 despite its severe structural changes still localizes to the cell surface and mediates functional activity of CXCL11. (PMID:15528361)
• LMP1-mediated p38/SAPK2 activation induces expression of the chemokine IP-10 and regulates transcript stability (PMID:15578697)
• Once induced in memory B cells, CXCR3 expression remains part of the individual cellular memory (PMID:15687242)
• studies suggest that IRBP and S-Ag can initiate innate and, in sensitive individuals, adaptive immune response by attracting iDCs and T and B cells expressing CXCR3 and CXCR5 (PMID:15713799)
• These data indicate that IFN-gamma mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation. (PMID:15725351)
• Marked up-regulation of IP-10 may predict the initial graft injury and the onset of delayed graft function in kidney transplantation. (PMID:15808644)
• CXCR3/IP-10 signaling is associated with the pathogenesis of human myasthenia gravis. (PMID:15843529)
• recruitment of T cells expressing Cxcr3 into the invasive margin of colorectal cancer. (PMID:15856455)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	cxcr3.1	ENSDARG00000007358
danio_rerio	cxcr3.3	ENSDARG00000070669
mus_musculus	Cxcr3	ENSMUSG00000050232
rattus_norvegicus	Cxcr3	ENSRNOG00000003305

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), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451)

Protein

Protein identifiers

C-X-C chemokine receptor type 3 — P49682 (reviewed: P49682)

Alternative names: CKR-L2, G protein-coupled receptor 9, Interferon-inducible protein 10 receptor

All UniProt accessions (1): P49682

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for the C-X-C chemokine CXCL9, CXCL10 and CXCL11 and mediates the proliferation, survival and angiogenic activity of human mesangial cells (HMC) through a heterotrimeric G-protein signaling pathway. Binds to CCL21. Probably promotes cell chemotaxis response. Upon activation by PF4, induces activated T-lymphocytes migration mediated via downstream Ras/extracellular signal-regulated kinase (ERK) signaling. Receptor for the C-X-C chemokine CXCL4 and also mediates the inhibitory activities of CXCL9, CXCL10 and CXCL11 on the proliferation, survival and angiogenic activity of human microvascular endothelial cells (HMVEC) through a cAMP-mediated signaling pathway. Does not promote cell chemotaxis respons. Interaction with CXCL4 or CXCL10 leads to activation of the p38MAPK pathway and contributes to inhibition of angiogenesis. Overexpression in renal cancer cells down-regulates expression of the anti-apoptotic protein HMOX1 and promotes apoptosis. Mediates the activity of CXCL11.

Subunit / interactions. Homomer. Forms heteromers with ACKR4. Interacts with PF4/CXCL4. Interacts with PF4/CXCL4.

Subcellular location. Cell membrane Cell membrane.

Tissue specificity. Isoform 1 and isoform 2 are mainly expressed in heart, kidney, liver and skeletal muscle. Isoform 1 is also expressed in placenta. Isoform 2 is expressed in endothelial cells. Expressed in T-cells (at protein level).

Post-translational modifications. Sulfation on Tyr-27 and Tyr-29 is essential for CXCL10 binding and subsequent signal transduction induction. N-glycosylated.

Miscellaneous. Due to exon skipping.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P49682-1	1, CXCR3-A	yes
P49682-2	2, CXCR3-B
P49682-3	3, CXCR3-alt

RefSeq proteins (2): NP_001136269, NP_001495* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR004070	Chemokine_CXCR3	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (62 total): mutagenesis site 17, helix 10, topological domain 8, transmembrane region 7, turn 4, modified residue 2, glycosylation site 2, splice variant 2, sequence variant 2, sequence conflict 2, strand 2, chain 1, region of interest 1, compositionally biased region 1, disulfide bond 1

Structure

Experimental structures (PDB)

15 structures.

PDB	Method	Resolution (Å)
8HNM	ELECTRON MICROSCOPY	2.94
9P0M	ELECTRON MICROSCOPY	2.95
8HNL	ELECTRON MICROSCOPY	2.98
8K2W	ELECTRON MICROSCOPY	3
8HNK	ELECTRON MICROSCOPY	3.01
8XYK	ELECTRON MICROSCOPY	3.03
8Y0N	ELECTRON MICROSCOPY	3.07
9P0L	ELECTRON MICROSCOPY	3.1
8XYI	ELECTRON MICROSCOPY	3.16
8K2X	ELECTRON MICROSCOPY	3.2
8XXZ	ELECTRON MICROSCOPY	3.3
9P0K	ELECTRON MICROSCOPY	3.5
8Y0H	ELECTRON MICROSCOPY	3.53
8HNN	ELECTRON MICROSCOPY	3.6
8XXY	ELECTRON MICROSCOPY	3.68

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P49682-F1	80.35	0.45

Antibody-complex structures (SAbDab): 7 — 8HNK, 8HNL, 8HNM, 8HNN, 8K2W, 8K2X, 8XXZ

Functional residue map

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

Post-translational modifications (2): 27, 29

Disulfide bonds (1): 124–203

Glycosylation sites (2): 22, 32

Mutagenesis-validated functional residues (17):

Position	Phenotype
1–16	reduces binding to cxcl10 and cxcl11, and reduces cxcl10- and cxcl11-induced chemotaxis and activation. does not affect
4	does not affect binding to cxcl9, cxcl10 and cxcl11 or activation.
21	reduces slightly cxcl9-, cxcl10- and cxcl11-induced chemotaxis.
27–29	abolishes binding to cxcl10 and cxcl11 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis.
27	reduces sulfation and cxcl9-, cxcl10- and cxcl11-induced chemotaxis. abolishes binding to cxcl10. abolishes sulfation, b
29	reduces sulfation, binding to cxcl10 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis. abolishes sulfation, binding to
112	abolishes binding to cxcl10 and cxcl11. reduces cxcl9-, cxcl10- and cxcl11-induced chemotaxis.
112	abolishes binding to cxcl10 and cxcl11 and cxcl10- and cxcl11-induced chemotaxis. reduces cxcl9-induced chemotaxis.
197	abolishes binding to cxcl10 and cxcl11 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis. reduces ligand-induced recepto
212	abolishes cxcl10-induced chemotaxis. reduces cxcl9- and cxcl11-induced chemotaxis. does not affect binding to cxcl10 and
216	reduces cxcl9-, cxcl10- and cxcl11-induced chemotaxis. does not affect binding to cxcl10 and cxcl11 or receptor internal
278	abolishes binding to cxcl10 and cxcl11 and cxcl11-induced chemotaxis. reduces cxcl9 and cxcl10-induced chemotaxis.
278	abolishes binding to cxcl10 and cxcl11 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis.
282	reduces binding to cxcl10 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis. abolishes binding to cxcl11.
282	reduces binding to cxcl10 and cxcl11 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis.
293	reduces binding to cxcl10 and cxcl9- and cxcl11-induced chemotaxis. abolishes binding to cxcl11 and cxcl10-induced chemo
293	abolishes binding to cxcl10 and cxcl11 and cxcl9-, cxcl10- and cxcl11-induced chemotaxis.

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-9942503	Differentiation of naive CD4+ T cells to T helper 1 cells (Th1 cells)

MSigDB gene sets: 335 (showing top): GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, PEREZ_TP63_TARGETS, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOCC_CELL_SURFACE, RACCACAR_AML_Q6, GOBP_REGULATION_OF_LEUKOCYTE_MIGRATION, GOBP_POSITIVE_REGULATION_OF_TRANSMEMBRANE_TRANSPORT, GOBP_MONOATOMIC_CATION_TRANSPORT, GOLDRATH_ANTIGEN_RESPONSE, GOBP_LEUKOCYTE_CHEMOTAXIS, GOBP_POSITIVE_REGULATION_OF_RELEASE_OF_SEQUESTERED_CALCIUM_ION_INTO_CYTOSOL

GO Biological Process (26): angiogenesis (GO:0001525), negative regulation of endothelial cell proliferation (GO:0001937), regulation of leukocyte migration (GO:0002685), apoptotic process (GO:0006915), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cell adhesion (GO:0007155), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), adenylate cyclase-activating G protein-coupled receptor signaling pathway (GO:0007189), positive regulation of cytosolic calcium ion concentration (GO:0007204), positive regulation of cell population proliferation (GO:0008284), T cell chemotaxis (GO:0010818), negative regulation of angiogenesis (GO:0016525), calcium-mediated signaling (GO:0019722), regulation of cell adhesion (GO:0030155), positive regulation of angiogenesis (GO:0045766), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of chemotaxis (GO:0050921), positive regulation of release of sequestered calcium ion into cytosol (GO:0051281), cell chemotaxis (GO:0060326), negative regulation of execution phase of apoptosis (GO:1900118), positive regulation of execution phase of apoptosis (GO:1900119), signal transduction (GO:0007165), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (9): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-X-C chemokine receptor activity (GO:0016494), chemokine binding (GO:0019956), C-C chemokine binding (GO:0019957), C-X-C chemokine binding (GO:0019958), signaling receptor activity (GO:0038023), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (5): cytoplasm (GO:0005737), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chemokine binding	3
cellular anatomical structure	3
signal transduction	2
angiogenesis	2
regulation of angiogenesis	2
chemokine receptor activity	2
blood vessel morphogenesis	1
anatomical structure formation involved in morphogenesis	1
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
negative regulation of epithelial cell proliferation	1
regulation of immune system process	1
regulation of cell migration	1
leukocyte migration	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
G protein-coupled receptor activity	1
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	1
adenylate cyclase activator activity	1
regulation of biological quality	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
lymphocyte chemotaxis	1
T cell migration	1
negative regulation of blood vessel morphogenesis	1
intracellular signaling cassette	1
cell adhesion	1
regulation of cellular process	1
positive regulation of vasculature development	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1

Protein interactions and networks

STRING

2178 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CXCR3	CXCL10	P02778	999
CXCR3	CXCL11	O14625	999
CXCR3	CXCL9	Q07325	999
CXCR3	CCL5	P13501	996
CXCR3	CXCL12	P48061	996
CXCR3	CCL2	P13500	995
CXCR3	PF4	P02776	995
CXCR3	CXCL8	P10145	994
CXCR3	CCL21	O00585	992
CXCR3	CCL3	P10147	992
CXCR3	CCL4	P13236	985
CXCR3	CCL20	P78556	983
CXCR3	PF4V1	P10720	977
CXCR3	CX3CL1	P78423	975
CXCR3	CXCL13	O43927	966

IntAct

31 interactions, top by confidence:

A	B	Type	Score
CXCR3	CLDN19	psi-mi:“MI:0915”(physical association)	0.560
CXCR3	TMEM14A	psi-mi:“MI:0915”(physical association)	0.560
C2CD2L	CXCR3	psi-mi:“MI:0915”(physical association)	0.560
CXCR3	CXCR4	psi-mi:“MI:0915”(physical association)	0.510
CXCR3	CXCR4	psi-mi:“MI:2364”(proximity)	0.510
CXCR4	CXCR3	psi-mi:“MI:2364”(proximity)	0.510
CXCR3	CXCR3	psi-mi:“MI:2364”(proximity)	0.460
CXCR3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
CXCR3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CXCR3	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	CXCR3	psi-mi:“MI:0915”(physical association)	0.400
CXCR3	GHDC	psi-mi:“MI:0914”(association)	0.350
CXCR3	RIMOC1	psi-mi:“MI:0914”(association)	0.350
Arrb2	CXCR3	psi-mi:“MI:2364”(proximity)	0.270
ACKR4	CXCR3	psi-mi:“MI:2364”(proximity)	0.270
TMEM14A	CXCR3	psi-mi:“MI:0915”(physical association)	0.000
C2CD2L	CXCR3	psi-mi:“MI:0915”(physical association)	0.000
CLDN19	CXCR3	psi-mi:“MI:0915”(physical association)	0.000
CXCR3	TMEM14A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (13): FATE1 (Two-hybrid), CXCL10 (Reconstituted Complex), PF4 (Reconstituted Complex), CXCL9 (Reconstituted Complex), CXCL11 (Reconstituted Complex), CXCR3 (Two-hybrid), CXCR3 (Two-hybrid), CXCR3 (Two-hybrid), CXCL9 (Reconstituted Complex), CXCL13 (Reconstituted Complex), CXCR3 (Affinity Capture-MS), USP35 (Affinity Capture-Western), CXCR3 (Affinity Capture-Western)

ESM2 similar proteins: A0T2N3, F7EQ49, O08878, O70526, O88410, O88855, P30411, P46093, P46663, P48146, P49220, P49681, P49682, P49684, P50132, P51680, P51686, P56484, P79960, P97583, Q15722, Q1JQB3, Q1WLP9, Q28642, Q2TAD5, Q3BCU0, Q3T181, Q4KLH9, Q4VA82, Q56UD9, Q5KSK8, Q5MD61, Q61125, Q7SZP9, Q867B2, Q8BMP4, Q8BUD0, Q8HZN9, Q8HZP1, Q8HZP2

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

3 interactions.

A	Effect	B	Mechanism
CXCL10	“up-regulates activity”	CXCR3	binding
CXCL9	“up-regulates activity”	CXCR3	binding
CXCL11	“up-regulates activity”	CXCR3	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	7
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

252 predictions. Top by Δscore:

Variant	Effect	Δscore
X:71618433:CTTA:C	donor_loss	1.0000
X:71618434:TTACC:T	donor_loss	1.0000
X:71618435:TACC:T	donor_loss	1.0000
X:71618436:ACC:A	donor_loss	1.0000
X:71617455:CTCAC:C	acceptor_gain	0.9900
X:71618432:ACTT:A	donor_loss	0.9900
X:71618436:A:AC	donor_gain	0.9900
X:71618437:C:CC	donor_gain	0.9900
X:71618437:CCT:C	donor_gain	0.9900
X:71617457:CAC:C	acceptor_gain	0.9800
X:71617459:CCT:C	acceptor_loss	0.9800
X:71617460:C:A	acceptor_loss	0.9800
X:71617461:T:C	acceptor_loss	0.9800
X:71618431:CACTT:C	donor_loss	0.9800
X:71617458:AC:A	acceptor_gain	0.9600
X:71617459:CC:C	acceptor_gain	0.9600
X:71617600:T:TA	donor_gain	0.9600
X:71617456:TCAC:T	acceptor_gain	0.9400
X:71617457:CACC:C	acceptor_gain	0.9400
X:71617462:G:GC	acceptor_gain	0.9100
X:71617460:C:CC	acceptor_gain	0.9000
X:71617548:CT:C	donor_gain	0.8900
X:71617470:G:T	acceptor_gain	0.8800
X:71617601:C:A	donor_gain	0.8700
X:71617469:C:CT	acceptor_gain	0.8600
X:71617562:T:TA	donor_gain	0.8600
X:71617701:CCC:C	acceptor_gain	0.8600
X:71617702:CCC:C	acceptor_gain	0.8600
X:71617476:G:T	acceptor_loss	0.8400
X:71618436:AC:A	donor_gain	0.8400

AlphaMissense

2337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:71617034:G:C	S146R	0.996
X:71617034:G:T	S146R	0.996
X:71617036:T:G	S146R	0.996
X:71616680:A:C	F264L	0.995
X:71616680:A:T	F264L	0.995
X:71616682:A:G	F264L	0.995
X:71617121:C:A	W117C	0.995
X:71617121:C:G	W117C	0.995
X:71616864:C:G	C203S	0.992
X:71616865:A:T	C203S	0.992
X:71616497:G:C	F325L	0.991
X:71616497:G:T	F325L	0.991
X:71616499:A:G	F325L	0.991
X:71617101:C:G	C124S	0.989
X:71617102:A:T	C124S	0.989
X:71616946:A:G	W176R	0.988
X:71616946:A:T	W176R	0.988
X:71617070:G:C	N134K	0.988
X:71617070:G:T	N134K	0.988
X:71617101:C:T	C124Y	0.987
X:71616663:G:T	P270H	0.986
X:71617123:A:G	W117R	0.986
X:71617123:A:T	W117R	0.986
X:71616863:G:C	C203W	0.985
X:71617273:C:G	G67R	0.985
X:71617273:C:T	G67R	0.985
X:71616864:C:T	C203Y	0.984
X:71616865:A:G	C203R	0.984
X:71617259:G:C	N71K	0.983
X:71617259:G:T	N71K	0.983

dbSNP variants (sampled 300 via entrez): RS1003951195 (X:71619088 C>T), RS1004086764 (X:71618592 C>G,T), RS1004470882 (X:71617658 T>C), RS1005095693 (X:71615500 G>T), RS1005472899 (X:71620010 C>G), RS1006089840 (X:71619603 A>T), RS1007308532 (X:71620151 C>G), RS1008119303 (X:71619887 G>A), RS1008601986 (X:71616268 G>A,C), RS1009155275 (X:71617558 C>T), RS1009637143 (X:71618925 A>G), RS1013992532 (X:71616480 A>G), RS1014090102 (X:71615453 C>T), RS1015033758 (X:71616619 C>T), RS1015169579 (X:71617253 C>A,T)

Disease associations

OMIM: gene MIM:300574 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): intellectual disability (MONDO:0001071)

Orphanet (1): NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4441 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 85 (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
CHEMBL523900	MELETIMIDE	2	85

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 (18 total), top 18:

Ligand	Action	Affinity	Parameter
CXCL11	Full agonist	10.5	pKi
CXCL10	Full agonist	9.8	pKi
NBI-74330	Antagonist	8.8	pKi
ACT-660602	Antagonist	8.57	pIC50
ACT-777991	Antagonist	8.34	pKd
CXCL9	Full agonist	8.3	pKi
AMG487	Antagonist	8.1	pIC50
CCL11	Antagonist	7.2	pKi
CCL13	Full agonist	7.2	pKi
duramycin	Antagonist	7.0	pIC50
CCL20	Full agonist	6.8	pKi
CCL7	Antagonist	6.6	pKi
CXCL12α	Full agonist	6.4	pKi
CCL5	Full agonist	6.4	pKi
dioscin	Antagonist	6.3	pIC50
CCL19	Full agonist	5.9	pKi
hypoglaucin A	Antagonist	5.7	pIC50
kallstroemin D	Antagonist	5.5	pIC50

Binding affinities (BindingDB)

672 measured of 683 human assays (683 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(4-chloropyrazol-1-yl)ethanone	IC50	0.1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(5-methylpyrazol-1-yl)ethanone	IC50	0.1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-[6-(2-aminoethyl)-1H-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3,5-dimethyl-1,2,4-triazol-1-yl)ethanone	IC50	0.1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-chloro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	IC50	0.2 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-c]pyridin-1-ylethanone	IC50	0.2 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-methylpyrazol-1-yl)ethanone	IC50	0.2 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-4-[4-(1H-imidazo[4,5-b]pyridin-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone	IC50	0.3 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[2-[(2R)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-3,3-difluoroindol-2-one	IC50	0.3 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(5,6-difluoro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	0.4 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(6-methyl-3-pyridinyl)ethanone	IC50	0.4 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(5-chloro-4-methyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	0.5 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-fluoro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	0.5 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazol-1-ylethanone	IC50	0.5 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-{(R)-4-[4-(2-Cyclopropyl-pyrimidin-5-yl)-2-trifluoromethyl-thiazol-5-yl]-2-methyl-piperazin-1-yl}-2-(3-isopropyl-[1,2,4]triazol-1-yl)-ethanone	IC50	0.7 nM	US-10047080
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[2-(2-propylpyrimidin-5-yl)-3,4-dihydro-1H-isoquinolin-8-yl]piperazin-1-yl]ethanone	IC50	0.85 nM	US-9951063: 8-(piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinoline derivatives
2-[3-(1-Hydroxy-ethyl)-[1,2,4]triazol-1-yl]-1-{(R)-2-methyl-4-[2-trifluoromethyl-4-(2-trifluoromethyl-pyrimidin-5-yl)-thiazol-5-yl]-piperazin-1-yl}-ethanone	IC50	0.9 nM	US-10047080
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[2-(6-methyl-3-pyridinyl)-3,4-dihydro-1H-isoquinolin-8-yl]piperazin-1-yl]ethanone	IC50	0.97 nM	US-9951063: 8-(piperazin-1-yl)-1,2,3,4-tetrahydro-isoquinoline derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-ethylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-2-methyl-4-[4-(4-methyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-tert-butyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(4,5-difluoro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2S,6R)-4-[4-(6-chloro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2,6-dimethylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-bromo-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-chloro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
3-[2-[(2R)-4-[4-(6-chloro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-1,3-benzoxazol-2-one	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[4-(6-methyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-tert-butyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(5-chloro-6-methyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[4-(6-propan-2-yl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(5-chloro-6-fluoro-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[4-[6-(trifluoromethyl)-1H-benzimidazol-2-yl]-1,3-thiazol-5-yl]piperazin-1-yl]ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-[5-chloro-6-(trifluoromethyl)-1H-benzimidazol-2-yl]-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-ethyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[4-(6-phenyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[2-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-3H-indol-2-one	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
3-[2-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-oxoethyl]-1H-imidazo[4,5-b]pyridin-2-one	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrazolo[5,4-b]pyridin-1-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-(3-chloropyrrolo[2,3-b]pyridin-1-yl)ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-ethyl-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-chloro-1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-[6-(hydroxymethyl)-1H-benzimidazol-2-yl]-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-cyclopropyl-1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-[6-(2-hydroxyethoxy)-1H-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-(6-acetyl-1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
1-[(2R)-4-[4-[6-(1-hydroxyethyl)-1H-benzimidazol-2-yl]-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
methyl 2-[5-[(3R)-4-(2-imidazo[4,5-b]pyridin-3-ylacetyl)-3-methylpiperazin-1-yl]-2-(trifluoromethyl)-1,3-thiazol-4-yl]-3H-benzimidazole-5-carboxylate	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-imidazo[4,5-b]pyridin-3-yl-1-[(2R)-2-methyl-4-[4-(7H-purin-8-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]piperazin-1-yl]ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives
2-(benzimidazol-1-yl)-1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]ethanone	IC50	1 nM	US-9266876: 4-(benzoimidazol-2-yl)-thiazole compounds and related aza derivatives

ChEMBL bioactivities

2602 potent at pChembl≥5 of 2625 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL3924716
10.00	IC50	0.1	nM	CHEMBL3944008
10.00	IC50	0.1	nM	CHEMBL3905581
9.70	IC50	0.2	nM	CHEMBL1681882
9.70	IC50	0.2	nM	CHEMBL3898933
9.70	IC50	0.2	nM	CHEMBL3949279
9.70	IC50	0.2	nM	CHEMBL3912920
9.70	IC50	0.1995	nM	CHEMBL3937630
9.52	IC50	0.3	nM	CHEMBL3116468
9.52	IC50	0.3	nM	CHEMBL3899279
9.52	IC50	0.3	nM	CHEMBL3909429
9.52	IC50	0.3	nM	CHEMBL472288
9.52	IC50	0.3	nM	CHEMBL1921863
9.52	IC50	0.3	nM	CHEMBL1921866
9.50	Ki	0.3162	nM	CHEMBL5288978
9.50	Ki	0.3162	nM	CHEMBL1681882
9.40	Ki	0.4	nM	CHEMBL1921858
9.40	IC50	0.4	nM	CHEMBL3116476
9.40	IC50	0.4	nM	CHEMBL3894522
9.40	IC50	0.4	nM	CHEMBL3970456
9.40	IC50	0.4	nM	CHEMBL256589
9.40	IC50	0.4	nM	CHEMBL1077831
9.40	IC50	0.4	nM	CHEMBL1921865
9.30	IC50	0.5	nM	CHEMBL3971111
9.30	IC50	0.5	nM	CHEMBL3986477
9.30	IC50	0.5	nM	CHEMBL3982804
9.22	IC50	0.6	nM	CHEMBL1077831
9.15	IC50	0.7	nM	CHEMBL403036
9.15	IC50	0.7	nM	CHEMBL5784337
9.10	IC50	0.8	nM	CHEMBL3116487
9.10	IC50	0.8	nM	CHEMBL1921858
9.10	IC50	0.8	nM	CHEMBL254083
9.10	Ki	0.7943	nM	CHEMBL1921858
9.10	IC50	0.8	nM	CHEMBL1077831
9.10	IC50	0.8	nM	CHEMBL1921864
9.07	IC50	0.85	nM	CHEMBL6012115
9.05	IC50	0.9	nM	CHEMBL5931191
9.05	IC50	0.9	nM	CHEMBL578187
9.05	IC50	0.9	nM	CHEMBL570665
9.05	IC50	0.9	nM	CHEMBL578192
9.05	IC50	0.9	nM	CHEMBL576097
9.05	IC50	0.9	nM	CHEMBL1921868
9.05	IC50	0.9	nM	CHEMBL1921879
9.01	IC50	0.97	nM	CHEMBL5748953
9.00	IC50	1	nM	CHEMBL3116486
9.00	IC50	1	nM	CHEMBL3967981
9.00	IC50	1	nM	CHEMBL3975264
9.00	IC50	1	nM	CHEMBL3974991
9.00	IC50	1	nM	CHEMBL3905608
9.00	IC50	1	nM	CHEMBL3914293

PubChem BioAssay actives

1633 with measured affinity, of 2133 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
5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-ethylpyridine-3-carboxamide	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0002	uM
1-[(2S)-4-[4-(1H-benzimidazol-2-yl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-pyrrolo[2,3-b]pyridin-1-ylethanone	1953215: Antagonist activity at CXCR3 (unknown origin) assessed as reduction in CXCL10 induced calcium flux by FLIPR method	ic50	0.0002	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-methylpyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0003	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-(2-hydroxypropyl)pyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0003	uM
5-[5-[(2R,5S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-5-ethyl-2-methylpiperazin-1-yl]-6-methylpyrazin-2-yl]-N-ethyl-1,3,4-oxadiazol-2-amine	1953221: Displacement of [125I]-CXCL10 from CXCR3 in human PBMC cells	ki	0.0003	uM
5-chloro-6-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-ethylpyridine-3-carboxamide	577822: Antagonist activity at human CXCR3	ic50	0.0003	uM
(2S)-1-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-4-[3-chloro-5-(1H-imidazol-2-yl)-2-pyridinyl]-2-ethylpiperazine	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0003	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]pyrazine-2-carboxamide	707874: Binding affinity to CXCR3	ki	0.0004	uM
5-chloro-6-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)pyrazin-2-amine	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0004	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-(2-hydroxyethyl)pyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0004	uM
N-[(1R)-1-[1-(4-ethoxyphenyl)-4-phenylimidazol-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamide	315706: Displacement of [125I]IP10 from human recombinant CXCR3 receptor expressed in IL2-activated human PBMC	ic50	0.0004	uM
N-(2-ethylsulfonylethyl)-2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-[(1R)-1-[4-oxo-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidin-2-yl]ethyl]acetamide	468556: Antagonist activity against human CXCR3 expressed in human PBMC assessed as inhibition of cell migration in response to IP10 in buffer	ic50	0.0004	uM
N-[(1R)-1-[1-(4-cyanophenyl)-4-phenylimidazol-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamide	315706: Displacement of [125I]IP10 from human recombinant CXCR3 receptor expressed in IL2-activated human PBMC	ic50	0.0007	uM
(2-amino-6-chloro-3-pyridinyl)-[4-[(2S)-4-[3-chloro-5-[5-(ethylamino)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-2-ethylpiperazin-1-yl]piperidin-1-yl]methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0008	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-(2,2,2-trifluoroethyl)pyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0008	uM
N-[(1R)-1-[3-(4-cyanophenyl)quinolin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamide	313782: Displacement of [125I]IP-10 from CXCR3 receptor expressed in human PBMC in RPMI-1640 buffer supplemented with 0.5% BSA	ic50	0.0008	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-cyclopropylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-[(1,1-dioxothian-4-yl)methyl]-2-[3-fluoro-4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0009	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-methoxyimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0009	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-cyclopropylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0009	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-cyclopropylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-[(1,1-dioxothian-4-yl)methyl]-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0009	uM
5-[(3S)-4-[1-(2-amino-6-chloropyridine-3-carbonyl)piperidin-4-yl]-3-ethylpiperazin-1-yl]-6-chloro-N-propan-2-ylpyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0009	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-[2-(trifluoromethylsulfonylamino)ethyl]pyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0009	uM
[4-[(2S)-4-[6-amino-3-chloro-5-[5-(ethylamino)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-2-ethylpiperazin-1-yl]piperidin-1-yl]-(2-amino-6-chloro-3-pyridinyl)methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0010	uM
N-[(1R)-1-[3-(4-ethoxyphenyl)-4-oxoquinazolin-2-yl]ethyl]-2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-(pyridin-3-ylmethyl)acetamide	315706: Displacement of [125I]IP10 from human recombinant CXCR3 receptor expressed in IL2-activated human PBMC	ic50	0.0010	uM
N-[(1R)-1-[3-(4-ethoxyphenyl)-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-2-[4-fluoro-3-(trifluoromethyl)phenyl]-N-(1-propan-2-ylpiperidin-4-yl)acetamide	468547: Displacement of [125I]-1P10 from human CXCR3 expressed in PBMC after 2 hrs in RPMI buffer by scintillation counting	ic50	0.0010	uM
N-[(1R)-1-[3-(4-ethoxyphenyl)-4-oxopyrido[2,3-d]pyrimidin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[4-fluoro-3-(trifluoromethyl)phenyl]acetamide	468547: Displacement of [125I]-1P10 from human CXCR3 expressed in PBMC after 2 hrs in RPMI buffer by scintillation counting	ic50	0.0010	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-ethylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0011	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-cyclopropylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-[(1,1-dioxothian-4-yl)methyl]-2-[4-(trifluoromethoxy)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0011	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-cyclopropylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-[(1,1-dioxothian-4-yl)methyl]-2-[3-(trifluoromethoxy)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0011	uM
5-[(3S)-4-[1-(4-chlorobenzoyl)piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-cyclopropyl-6-methylpyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0011	uM
(2-amino-6-chloro-3-pyridinyl)-[4-[(2S)-2-ethyl-4-[5-[5-(ethylamino)-1,3,4-oxadiazol-2-yl]-3-methylpyrazin-2-yl]piperazin-1-yl]piperidin-1-yl]methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0012	uM
5-[(3S)-4-[1-(2-amino-6-chloropyridine-3-carbonyl)piperidin-4-yl]-3-ethylpiperazin-1-yl]-6-chloro-N-cyclopropylpyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0012	uM
(4-chlorophenyl)-[4-[(2S)-2-ethyl-4-[5-[5-(ethylamino)-1,3,4-oxadiazol-2-yl]-3-methylpyrazin-2-yl]piperazin-1-yl]piperidin-1-yl]methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0012	uM
(2S)-4-[3-chloro-5-(4,5-dihydro-1H-imidazol-2-yl)-2-pyridinyl]-1-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-2-ethylpiperazine	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0013	uM
[4-[(2S)-4-[6-amino-5-(5-amino-1,3,4-oxadiazol-2-yl)-3-chloropyrazin-2-yl]-2-ethylpiperazin-1-yl]piperidin-1-yl]-(2-amino-6-chloro-3-pyridinyl)methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0013	uM
(2S)-1-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-4-[3-chloro-5-(furan-2-yl)-2-pyridinyl]-2-ethylpiperazine	1953221: Displacement of [125I]-CXCL10 from CXCR3 in human PBMC cells	ki	0.0013	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-cyclopropylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-[(1,1-dioxothian-4-yl)methyl]-2-[4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0013	uM
5-[(2R,5S)-4-[1-(4-chlorobenzoyl)piperidin-4-yl]-5-ethyl-2-methylpiperazin-1-yl]-N-cyclopropyl-6-methylpyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0013	uM
2-hydroxy-N,N-dimethyl-3-[[2-[[(5-methylfuran-2-yl)-(2-methyloxolan-2-yl)methyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide	1953216: Antagonist activity at CXCR3 (unknown origin)	ic50	0.0013	uM
2-[5-chloro-6-[(3S)-4-[1-[(4-chloro-2-fluorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-3-pyridinyl]-1,3,4-oxadiazole	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0014	uM
N-[1-[3-(4-cyanophenyl)-8-(dimethylamino)imidazo[1,2-a]pyrazin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0014	uM
3-amino-6-chloro-5-[(3S)-4-[1-[(4-chlorophenyl)methyl]piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-[(3R)-2-oxooxolan-3-yl]pyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0015	uM
(2-amino-6-chloro-3-pyridinyl)-[4-[(2S)-2-ethyl-4-[5-[5-(ethylamino)-1,3,4-oxadiazol-2-yl]-3-(trifluoromethyl)pyrazin-2-yl]piperazin-1-yl]piperidin-1-yl]methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0015	uM
5-[(3S)-4-[1-(2-amino-6-chloropyridine-3-carbonyl)piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-methyl-6-(trifluoromethyl)pyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0015	uM
5-[(3S)-4-[1-(2-amino-6-chloropyridine-3-carbonyl)piperidin-4-yl]-3-ethylpiperazin-1-yl]-N-tert-butyl-6-chloropyrazine-2-carboxamide	631980: Displacement of [125I]CXCL10 from human CXCR3 expressed in mouse BA/F3 cells	ic50	0.0015	uM
3-chloro-N-[2-[4-(2-imidazo[4,5-b]pyridin-3-ylacetyl)piperazin-1-yl]phenyl]benzamide	1874442: Antagonist activity at recombinant human CXCR3 expressed in human CHO-K1 cells co-expressing Galpha15 incubated for 10 mins by Fluo-4AM dye based FLIPR assay	ic50	0.0016	uM
N-[(1R)-1-[3-(4-cyanophenyl)-8-methylimidazo[1,2-a]pyrazin-2-yl]ethyl]-N-(2-ethylsulfonylethyl)-2-[3-fluoro-4-(trifluoromethyl)phenyl]acetamide	449699: Displacement of [125I]IP10 from CXCR3 receptor expressed in PBMC	ic50	0.0016	uM
(4-chlorophenyl)-[4-[(2S,5R)-2-ethyl-4-[5-(1H-imidazol-2-yl)-3-methylpyrazin-2-yl]-5-methylpiperazin-1-yl]piperidin-1-yl]methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0016	uM
1-[(2R)-4-[4-(1H-benzimidazol-2-yl)-2-(trifluoromethyl)-1,3-thiazol-5-yl]-2-methylpiperazin-1-yl]-2-imidazo[4,5-b]pyridin-3-ylethanone	1874442: Antagonist activity at recombinant human CXCR3 expressed in human CHO-K1 cells co-expressing Galpha15 incubated for 10 mins by Fluo-4AM dye based FLIPR assay	ic50	0.0016	uM
[4-[(2S)-4-[6-amino-3-chloro-5-[5-(methylamino)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-2-ethylpiperazin-1-yl]piperidin-1-yl]-(2-amino-6-chloro-3-pyridinyl)methanone	1067007: Binding affinity to human CXCR3 receptor	ic50	0.0016	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Calcium	affects binding, increases activity, increases uptake, increases abundance, increases expression (+1 more)	3
Nickel	increases expression	2
Asbestos, Serpentine	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
nickel chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, decreases expression, affects response to substance, increases expression	1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
abrine	increases expression	1
pevonedistat	affects expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Arsenic Trioxide	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Dichloroacetic Acid	increases expression	1
Dinitrochlorobenzene	increases expression	1
Diuron	decreases expression	1
Ethinyl Estradiol	affects cotreatment, increases expression	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression, affects cotreatment	1
Methyl Methanesulfonate	decreases expression	1
Nicotine	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Taurine	decreases expression	1

ChEMBL screening assays

193 unique, capped per target: 113 binding, 80 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003787	Functional	Antagonist activity at human CXCR3 expressed in CHO cells assessed as inhibition of ITAC-stimulated [35S]GTPgammaS binding pretreated 30 mins before ITAC challenge	Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists. — Bioorg Med Chem Lett
CHEMBL1003792	Binding	Displacement of [125I]ITAC from CXCR3 in PHA/IL-2 activated human PBMC pretreated 30 mins before [125I]ITAC challenge after 1 hr by liquid scintillation counter	Synthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

14 cell lines: 9 cancer cell line, 4 spontaneously immortalized cell line, 1 factor-dependent cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8ED	Abcam HCT 116 CXCR3 KO	Cancer cell line	Male
CVCL_B9GL	Abcam A-549 CXCR3 KO	Cancer cell line	Male
CVCL_D2ER	Abcam MCF-7 CXCR3 KO	Cancer cell line	Female
CVCL_E6MT	Genomeditech Ba/F3 H_CXCR3	Factor-dependent cell line
CVCL_E7UK	BOWES CXCR3 clone #1	Cancer cell line	Female
CVCL_E7UL	BOWES CXCR3 clone #2	Cancer cell line	Female
CVCL_E7UM	BOWES CXCR3 clone #3	Cancer cell line	Female
CVCL_KA15	CHO-K1/Galpha15/CXCR3	Spontaneously immortalized cell line	Female
CVCL_KV02	cAMP Hunter CHO-K1 CXCR3 Gi	Spontaneously immortalized cell line	Female
CVCL_KW79	PathHunter CHO-K1 CXCR3 beta-arrestin	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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