CCR3

Summary

CCR3 (C-C motif chemokine receptor 3, HGNC:1604) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor type 3 (P51677). G protein-coupled receptor (GPCR) that plays a key role in the immune system by regulating the migration and activation of white blood cells in response to chemokines.

The protein encoded by this gene is a receptor for C-C type chemokines. It belongs to family 1 of the G protein-coupled receptors. This receptor binds and responds to a variety of chemokines, including eotaxin (CCL11), eotaxin-3 (CCL26), MCP-3 (CCL7), MCP-4 (CCL13), and RANTES (CCL5). It is highly expressed in eosinophils and basophils, and is also detected in TH1 and TH2 cells, as well as in airway epithelial cells. This receptor may contribute to the accumulation and activation of eosinophils and other inflammatory cells in the allergic airway. It is also known to be an entry co-receptor for HIV-1. This gene and seven other chemokine receptor genes form a chemokine receptor gene cluster on the chromosomal region 3p21. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 1232 — RefSeq curated summary.

At a glance

• GWAS associations: 29
• Clinical variants (ClinVar): 61 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_178329

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1604
Approved symbol	CCR3
Name	C-C motif chemokine receptor 3
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CC-CKR-3, CKR3, CD193
Ensembl gene	ENSG00000183625
Ensembl biotype	protein_coding
OMIM	601268
Entrez	1232

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 7 protein_coding, 2 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000357422, ENST00000395940, ENST00000395942, ENST00000452454, ENST00000457243, ENST00000475150, ENST00000484025, ENST00000545097, ENST00000682778, ENST00000684109, ENST00000954508

RefSeq mRNA: 4 — MANE Select: NM_178329 NM_001164680, NM_001837, NM_178328, NM_178329

CCDS: CCDS2738, CCDS54574

Canonical transcript exons

ENST00000395940 — 2 exons

Exon	Start	End
ENSE00001523313	46265148	46266706
ENSE00001784949	46242460	46242538

Expression profiles

Bgee: expression breadth broad, 100 present calls, max score 85.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.5738 / max 335.9586, expressed in 165 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36439	0.7692	50
36435	0.2156	36
36438	0.1876	31
36436	0.1366	24
36437	0.1009	17
36426	0.0945	53
36427	0.0693	31

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	85.78	gold quality
blood	UBERON:0000178	82.66	gold quality
oocyte	CL:0000023	81.32	gold quality
hindlimb stylopod muscle	UBERON:0004252	80.16	gold quality
monocyte	CL:0000576	73.81	gold quality
mononuclear cell	CL:0000842	73.49	gold quality
leukocyte	CL:0000738	73.32	gold quality
gall bladder	UBERON:0002110	65.26	gold quality
vermiform appendix	UBERON:0001154	64.32	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	63.47	gold quality
biceps brachii	UBERON:0001507	62.76	silver quality
granulocyte	CL:0000094	62.31	gold quality
bone marrow	UBERON:0002371	62.20	gold quality
caecum	UBERON:0001153	60.59	gold quality
bone marrow cell	CL:0002092	59.72	silver quality
muscle of leg	UBERON:0001383	59.15	gold quality
triceps brachii	UBERON:0001509	58.82	silver quality
deltoid	UBERON:0001476	58.72	silver quality
rectum	UBERON:0001052	58.65	gold quality
muscle organ	UBERON:0001630	57.64	gold quality
gastrocnemius	UBERON:0001388	57.58	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	56.86	gold quality
decidua	UBERON:0002450	56.55	gold quality
muscle tissue	UBERON:0002385	54.60	gold quality
skeletal muscle tissue	UBERON:0001134	54.02	gold quality
spleen	UBERON:0002106	53.14	gold quality
smooth muscle tissue	UBERON:0001135	52.84	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
duodenum	UBERON:0002114	52.42	gold quality
skin of leg	UBERON:0001511	52.30	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	4.06

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): GATA1, NFKB1, RELA

miRNA regulators (miRDB)

31 targeting CCR3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-543	99.52	69.03	2595
HSA-MIR-6083	99.47	68.73	2393
HSA-MIR-5580-5P	99.38	66.96	1139
HSA-MIR-3911	99.38	66.95	1087
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6504-5P	99.26	65.95	1487
HSA-MIR-3064-5P	99.26	66.13	1497
HSA-MIR-3085-3P	99.26	66.16	1490
HSA-MIR-296-3P	99.21	66.56	474
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-6792-5P	98.39	68.16	1330
HSA-MIR-147A	98.33	66.40	795
HSA-MIR-6881-3P	98.04	68.24	1777
HSA-MIR-3977	98.00	68.17	1500
HSA-MIR-4423-3P	97.98	69.66	912
HSA-MIR-3190-3P	97.61	66.95	1406
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-4670-3P	97.37	68.35	1378
HSA-MIR-6841-5P	97.19	67.29	409
HSA-MIR-335-5P	97.10	68.12	1022

Literature-anchored findings (GeneRIF, showing 40)

• agonistic effect of truncated leukotactin-1 on receptor activity (PMID:11832479)
• Alanine scanning mutagenesis of CCR3 reveals that the three intracellular loops are essential for functional receptor expression. (PMID:11920572)
• bronchial expression up-regulated in exacerbations of chronic bronchitis (PMID:11991282)
• demonstrated that CCR3 is absent from the testes (PMID:11994538)
• downstream promoter element dependent, general transcription control mechanism is conserved between Drosophila and human genes (PMID:12079287)
• CCR3 is expressed by dendritic cells (DCs) differentiated from blood monocytes, DCs that emigrate from skin (epidermal and dermal DCs), and DCs derived from CD34+ hemopoietic precursors in bone marrow, umbilical cord blood, and leukapheresis collection. (PMID:12218106)
• results suggest that expression of chemokine receptor 3(CCR3) and its ligand eotaxin/CCL11 plays a role in the recruitment and retention of CD30(+) malignant T cells to the skin (PMID:12393570)
• This protein mobilizes to the surface of human mast cells and potentiates immunoglobulin E-dependent generation of interleukin 13. (PMID:12654630)
• Eosinophil CCR3 expression between atopic individuals does not correlate with atopy or serum IgE levels, nor is the status of macrophage-inflammatory protein-1alpha-highly responsive donors associated with increased chemattractant receptor expression. (PMID:12794150)
• 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)
• Ligation of CCR3 by eotaxin/chemokine ligand (CCL) 11 induces apoptosis in IL-2- and IL-4-stimulated primary CD19+ B cell cultures (approximately 40% apoptotic cells) as well as B cell lines, but has no effect on chemotaxis or cell adhesion. (PMID:12902471)
• Single nucleotide polymorphism is not associated with atopic dermatitis in Japanese. (PMID:14581140)
• the two N-terminal motifs of eotaxin must cooperate with other regions to successfully bind and activate CCR3 (PMID:14733956)
• examination of the role of epidermal growth factor receptor in CCR3 signaling (PMID:15219825)
• multiple residues on multiple extracellular domains of hCCR3 are important for coreceptor activity for HIV-1. (PMID:15476879)
• the restoration of CRTH2(chemoattractant receptor-homologous molecule expressed on Th2 cells)/CCR3 expression may be an indicator for optimal recovery after septic shock (PMID:15507393)
• The mouse transcription factor GATA-1 binds to transgenic human CCR3 exon 1. The 1.6-kb CCR3 promoter element, that includes exon 1, is a strong promoter in vivo. (PMID:15807893)
• Up-regulation of CCR3 by airway smooth muscle cells in asthmatic subjects might be partly responsible for the increased smooth muscle mass and the airway hyperresponsiveness in these patients. (PMID:16081847)
• CCR5 and CCR3 receptors are expressed on the head region of human spermatozoon (PMID:16174786)
• Epithelial CCR3 participates in key functions for wound repair (PMID:16920975)
• Chemokine (C-C-motif) receptor 3 (CCR3), playing an important role in endometrium related metabolic pathways, may influence the onset of menarche. (PMID:17146638)
• This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan. (PMID:17845580)
• The genetic association between CCR3 polymorphisms and the number of circulating eosinophils was revealed;it was more pronounced when the CCR3 polymorphisms were paired with polymorphisms in IL5RA. (PMID:17983872)
• The allergen-induced levels of beta(c) mRNA and CCR3 mRNA in sputum-derived cells were inhibited by TPI ASM8, with no significant effects on the cell surface protein expression of CCR3 and beta(c). (PMID:18244953)
• infiltrated neutrophils from patients with chronic inflammatory lung diseases and rheumatoid arthritis highly express CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 (PMID:19017998)
• Some CNS-tropic strains of HIV-1 utilize CCR5 as a co-receptor but do not need CCR3, while for other isolates both CCR3 and CCR5 may be required. (PMID:19218218)
• Signals evoked via the FPR caused unidirectional down-regulation of CCR3-mediated chemotaxis but not respiratory burst in human eosinophils. (PMID:19414538)
• the eosinophil/mast cell chemokine receptor CCR3 is specifically expressed in choroidal neovascular endothelial cells in humans with age-related macular degeneration (PMID:19525930)
• Investigated the regions 2q12 (IL18RAP) and 3p21 (CCR3)in regards to celiac disease risk in the Spanish population.Two SNPs, rs917997 (2q12) and rs6441961 (3p21), were genotyped; Assoc’n was found w/rs6441961, a non-sign. result was obtained for rs917997. (PMID:19542083)
• These results suggest that CCR3 may be used as a surrogate co-receptor by subtype B while FPRL1 may be used as a surrogate co-receptor by subtypes A and C HIV-1. (PMID:19553323)
• CENP-B binding stimulated the cross-talk between CCR3 and epidermal growth factor receptor (EGFR) in human pulmonary artery smooth muscle cells. (PMID:19714638)
• Our data support the notion that CCR3, CCR7, and CXCR4 are increasingly expressed in tumor cells from PTC and that CXCR4 expression in PTC could be a potential marker for enhanced tumor aggressiveness. (PMID:19731977)
• CCR3 genetic polymorphisms may contribute to the development of the aspirin exacerbated respiratory disease phenotype and may be used as a genetic marker for differentiating between the two major aspirin hypersensitivity phenotypes. (PMID:20022477)
• The present data are of interest with regard to the potential use of AZD3778 in allergic rhinitis and to the relative importance of eosinophil actions to the symptomatology of allergic rhinitis. (PMID:20144207)
• Data show that both plasma eotaxin level and expression of CCR3 on CD4+ T cells were higher in allergic patients than controls in different types of allergy. (PMID:20306659)
• data support the role of DCs in differential regulation of CCR3 and CCR4 on CD4+ T cells from HDM-sensitive and non-atopic asthmatics after Der p 1 exposure. (PMID:20364559)
• interaction of eotaxins and CCR3 regulates the Th2-dominant tumor environment, which is closely related to the development of cutaneous T-cell lymphoma (PMID:20505746)
• CCR3 is differentially expressed on inflammatory cells in rheumatoid arthritis, while eotaxin-2, a potent CCR3 agonist, is differentially expressed in active disease. (PMID:20659406)
• The T17C chemokine receptor 3 polymorphism appears to be associated with asthma BHR and disease severity but not with atopy. (PMID:20726325)
• GATA-1 controls CCR3 transcription by interacting dynamically with multiple GATA sites in the regulatory region of the CCR3 gene. (PMID:21041734)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	ccr11.1	ENSDARG00000070755
danio_rerio	ccr2	ENSDARG00000079829
danio_rerio	cabz01093075.1	ENSDARG00000086616
danio_rerio	ccr8.1	ENSDARG00000095789
danio_rerio	si:ch211-207g17.3	ENSDARG00000105363
danio_rerio	si:cabz01093077.1	ENSDARG00000105467
mus_musculus	Ccr3	ENSMUSG00000035448
rattus_norvegicus	Ccr3	ENSRNOG00000006736

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), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor type 3 — P51677 (reviewed: P51677)

Alternative names: Eosinophil eotaxin receptor

All UniProt accessions (3): P51677, Q8TDP4, Q8TDP5

UniProt curated annotations — full annotation on UniProt →

Function. G protein-coupled receptor (GPCR) that plays a key role in the immune system by regulating the migration and activation of white blood cells in response to chemokines. Selectively interacts with eosinophil-attracting chemokines such as eotaxin/CCL11, eotaxin-2/CCL24 and eotaxin-3/CCL26. Ligand binding triggers intracellular signaling that leads to chemotaxis of immune cells. Mechanistically, signals through GNA14 or GNA16 to induce stimulation of phospholipase Cbeta/PLCB2 and subsequently chemotaxis. Alternatively, transduces signal via GNAI1 resulting in elevated intracellular calcium levels and activation of the PI3K/AKT pathway. May also act as a possible functional receptor for NARS1. (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.

Subunit / interactions. Monomer. Homooligomer. Interacts with GNAI1. (Microbial infection) Interacts with HIV-1 protein Tat. (Microbial infection) Interacts with Kaposi virus protein vCCL2; this interaction promotes activation and chemotaxis of eosinophils. (Microbial infection) Interacts with HSRV major surface glycoprotein G; this interaction mediates virus infection of human airway epithelial cells.

Subcellular location. Cell membrane.

Tissue specificity. In eosinophils as well as trace amounts in neutrophils and monocytes.

Miscellaneous. Overexpression of CCR3 together with its ligands appears to be a characteristic of ulcerative colitis (UC). The production of CCR3 ligands by human colonic epithelial cells suggests further that the epithelium can play a role in modulating pathological T-cell-mediated mucosal inflammation.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P51677-1	1	yes
P51677-2	2

RefSeq proteins (4): NP_001158152, NP_001828, NP_847898, NP_847899* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR002238	Chemokine_CCR3	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (45 total): helix 15, topological domain 8, transmembrane region 7, sequence conflict 5, sequence variant 3, turn 3, chain 1, disulfide bond 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
7X9Y	ELECTRON MICROSCOPY	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51677-F1	83.72	0.59

Antibody-complex structures (SAbDab): 1 — 7X9Y

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): 106–183

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

ID	Pathway
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-162582	Signal Transduction
R-HSA-372790	Signaling by GPCR
R-HSA-373076	Class A/1 (Rhodopsin-like receptors)
R-HSA-375276	Peptide ligand-binding receptors
R-HSA-388396	GPCR downstream signalling
R-HSA-500792	GPCR ligand binding

MSigDB gene sets: 179 (showing top): GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOCC_CELL_SURFACE, GAURNIER_PSMD4_TARGETS, MORF_RAD51L3, GOBP_ADENYLATE_CYCLASE_MODULATING_G_PROTEIN_COUPLED_RECEPTOR_SIGNALING_PATHWAY, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, MODULE_289, MORF_CTSB, MORF_IL4, GOBP_BLOOD_VESSEL_MORPHOGENESIS

GO Biological Process (17): positive regulation of endothelial cell proliferation (GO:0001938), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cellular defense response (GO:0006968), cell adhesion (GO:0007155), adenylate cyclase-modulating G protein-coupled receptor signaling pathway (GO:0007188), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), positive regulation of angiogenesis (GO:0045766), cell chemotaxis (GO:0060326), chemokine-mediated signaling pathway (GO:0070098), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), cellular response to cytokine stimulus (GO:0071345)

GO Molecular Function (5): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (4): cytoplasm (GO:0005737), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

Category	Pathways
Signaling by GPCR	2
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
G protein-coupled receptor signaling pathway	4
defense response	2
cellular process	2
signal transduction	2
chemokine binding	2
cellular anatomical structure	2
endothelial cell proliferation	1
regulation of endothelial cell proliferation	1
positive regulation of epithelial cell proliferation	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
adenylate cyclase activity	1
phospholipase C activator activity	1
regulation of biological quality	1
intracellular signaling cassette	1
angiogenesis	1
regulation of angiogenesis	1
positive regulation of vasculature development	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
G protein-coupled receptor activity	1
response to cytokine	1
G protein-coupled chemoattractant receptor activity	1
cytokine receptor activity	1
chemokine-mediated signaling pathway	1
chemokine receptor activity	1
C-C chemokine binding	1
transmembrane signaling receptor activity	1
binding	1
intracellular anatomical structure	1
membrane	1

Protein interactions and networks

STRING

1720 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR3	CCL11	P50877	999
CCR3	CCL26	Q9Y258	999
CCR3	CCL24	O00175	999
CCR3	CCL5	P13501	999
CCR3	CCL7	P80098	996
CCR3	CCL3	P10147	996
CCR3	CCL4	P13236	996
CCR3	CCL2	P13500	995
CCR3	CCL13	Q99616	995
CCR3	CCL8	P78388	991
CCR3	CCL22	O00626	986
CCR3	CCR5	P51681	981
CCR3	CCR1	P32246	977
CCR3	CXCL10	P02778	975
CCR3	CCL3L1	P16619	971

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CCR3	CCL11	psi-mi:“MI:0915”(physical association)	0.400
CCL11	CCR3	psi-mi:“MI:0915”(physical association)	0.400
CCR3	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP1	CCR3	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CCR3	psi-mi:“MI:0915”(physical association)	0.400
CCR3	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CCR3	psi-mi:“MI:0915”(physical association)	0.400
CCR3	RAMP3	psi-mi:“MI:0915”(physical association)	0.400
CCR3	PRKCA	psi-mi:“MI:0914”(association)	0.350

BioGRID (10): FGR (Affinity Capture-Western), HCK (Affinity Capture-Western), CCL5 (Reconstituted Complex), CCL7 (Reconstituted Complex), CCL2 (Reconstituted Complex), CCL11 (Reconstituted Complex), CCR3 (Reconstituted Complex), CCR3 (Reconstituted Complex), PRKCA (Affinity Capture-MS), C10orf35 (Affinity Capture-MS)

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, F5HF62, O00590, O08556, O08707, O09027, O18793, O54689, O54814, O55193, O62743, O97571, O97665, O97878, O97879, O97880, O97881, O97882, O97883, O97962, O97975, P21109, P25025, P32246, P35344, P35411, P41597, P46094, P49238, P51675, P51676, P51677, P51678, P51679, P51680, P51681, P51682, P51683, P51684, P51685

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
CCL11	up-regulates	CCR3	binding
CCR3	up-regulates	ERK1/2
CCR3	up-regulates	p38
CCL5	up-regulates	CCR3	binding
NfKb-p65/p50	“up-regulates quantity by expression”	CCR3	“transcriptional regulation”
CCL11	“up-regulates activity”	CCR3	binding
CCR3	“up-regulates activity”	p38
CCR3	“up-regulates activity”	ERK1/2

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	6
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1586 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46208280:A:AC	donor_gain	1.0000
3:46208281:C:CC	donor_gain	1.0000
3:46208281:CT:C	donor_gain	1.0000
3:46208281:CTCT:C	donor_gain	1.0000
3:46208281:CTCTG:C	donor_gain	1.0000
3:46245395:G:GT	donor_gain	1.0000
3:46264479:T:G	donor_gain	1.0000
3:46163861:GG:G	donor_gain	0.9900
3:46163862:GG:G	donor_gain	0.9900
3:46204320:TTCTC:T	acceptor_gain	0.9900
3:46204322:CTC:C	acceptor_gain	0.9900
3:46204324:CCT:C	acceptor_loss	0.9900
3:46204325:C:CC	acceptor_gain	0.9900
3:46204325:CTA:C	acceptor_loss	0.9900
3:46208275:CACTT:C	donor_loss	0.9900
3:46208276:ACTTA:A	donor_loss	0.9900
3:46208277:CTTAC:C	donor_loss	0.9900
3:46208278:TTA:T	donor_loss	0.9900
3:46208279:TA:T	donor_loss	0.9900
3:46208280:ACT:A	donor_gain	0.9900
3:46208281:CTC:C	donor_gain	0.9900
3:46242401:GGA:G	acceptor_gain	0.9900
3:46244024:GA:G	donor_gain	0.9900
3:46244026:G:GG	donor_gain	0.9900
3:46244052:G:GT	donor_gain	0.9900
3:46244121:A:AG	donor_gain	0.9900
3:46263563:G:GT	donor_gain	0.9900
3:46264456:GTCC:G	donor_gain	0.9900
3:46163861:GGGTA:G	donor_loss	0.9800
3:46163862:GGTA:G	donor_loss	0.9800

AlphaMissense

2322 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:46265618:A:C	S154R	0.995
3:46265620:C:A	S154R	0.995
3:46265620:C:G	S154R	0.995
3:46265455:G:C	W99C	0.992
3:46265455:G:T	W99C	0.992
3:46265630:T:A	W158R	0.989
3:46265630:T:C	W158R	0.989
3:46265705:T:A	C183S	0.986
3:46265706:G:C	C183S	0.986
3:46265383:C:A	N75K	0.985
3:46265383:C:G	N75K	0.985
3:46265513:A:C	S119R	0.985
3:46265515:C:A	S119R	0.985
3:46265515:C:G	S119R	0.985
3:46265474:T:A	C106S	0.983
3:46265475:G:C	C106S	0.983
3:46265919:C:A	P254H	0.982
3:46265919:C:G	P254R	0.981
3:46266027:C:A	A290D	0.979
3:46266080:T:C	F308L	0.978
3:46266082:C:A	F308L	0.978
3:46266082:C:G	F308L	0.978
3:46265421:C:G	P88R	0.975
3:46265707:C:G	C183W	0.975
3:46265490:G:A	G111E	0.974
3:46265421:C:A	P88Q	0.973
3:46265453:T:A	W99R	0.973
3:46265453:T:C	W99R	0.973
3:46265790:C:G	P211R	0.973
3:46265912:T:A	W252R	0.973

dbSNP variants (sampled 300 via entrez): RS1000071842 (3:46229633 T>A), RS1000079016 (3:46247544 A>G), RS1000182626 (3:46224332 C>T), RS1000184298 (3:46244136 A>G), RS1000284988 (3:46231127 G>C), RS1000314360 (3:46259736 G>A), RS1000317671 (3:46217616 C>T), RS1000363301 (3:46217235 T>C), RS1000368687 (3:46236860 G>A), RS1000444392 (3:46230729 C>T), RS1000468241 (3:46224653 C>T), RS1000493626 (3:46243810 G>A,C), RS1000565480 (3:46243538 G>C), RS1000655088 (3:46238413 G>A,T), RS1000775215 (3:46237236 A>G)

Disease associations

OMIM: gene MIM:601268 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST000157_5	Celiac disease	3.000000e-07
GCST000612_32	Celiac disease	3.000000e-17
GCST001691_2	Monocyte chemoattractant protein-1 levels	7.000000e-09
GCST001762_308	Obesity-related traits	7.000000e-09
GCST001804_1	Behcet’s disease	4.000000e-13
GCST002520_6	Celiac disease	4.000000e-08
GCST002665_3	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2.000000e-13
GCST002912_1	Narcolepsy with cataplexy	6.000000e-06
GCST003043_90	Inflammatory bowel disease	4.000000e-08
GCST003045_10	Ulcerative colitis	9.000000e-10
GCST003045_18	Ulcerative colitis	1.000000e-08
GCST003654_6	Bone mineral density (Ward’s triangle area)	3.000000e-06
GCST004133_35	Ulcerative colitis	2.000000e-06
GCST004618_6	White blood cell count (basophil)	1.000000e-19
GCST004625_67	Monocyte count	4.000000e-25
GCST004631_61	Basophil percentage of white cells	4.000000e-20
GCST004634_22	Basophil percentage of granulocytes	2.000000e-16
GCST005523_14	Celiac disease	1.000000e-20
GCST005528_28	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	2.000000e-07
GCST005977_30	Monocyte count	7.000000e-14
GCST008489_15	Celiac disease	3.000000e-08
GCST008644_24	Celiac disease and Rheumatoid arthritis	2.000000e-11
GCST011569_1	Pancreatic beta-cell glucose sensitivity	7.000000e-07
GCST012073_4	Behcet’s disease	9.000000e-10
GCST90002379_38	Basophil count	3.000000e-72
GCST90002380_138	Basophil percentage of white cells	2.000000e-66
GCST90002381_146	Eosinophil count	1.000000e-13
GCST90002382_564	Eosinophil percentage of white cells	3.000000e-12
GCST90010715_7	Arthritis (juvenile idiopathic)	3.000000e-11

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0007785	femoral neck bone mineral density
EFO:0005090	basophil count
EFO:0005091	monocyte count
EFO:0007992	basophil percentage of leukocytes
EFO:0007995	basophil percentage of granulocytes
EFO:0006842	diabetes mellitus biomarker
EFO:0004842	eosinophil count
EFO:0007991	eosinophil percentage of leukocytes

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3473 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 139 (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
CHEMBL3670800	LAZUCIRNON	2	54
CHEMBL2105686	CENICRIVIROC MESYLATE	1	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 (25 total), top 25:

Ligand	Action	Affinity	Parameter
CCL13	Full agonist	10.3	pIC50
CCL11	Full agonist	10.0	pKi
CCL24	Full agonist	9.4	pIC50
CCL5	Full agonist	9.3	pKi
CCL7	Full agonist	9.2	pKi
RO116-9132/238	Antagonist	9.0	pIC50
CCL26	Full agonist	8.9	pIC50
CCL15	Full agonist	8.6	pIC50
CCL18	Antagonist	8.5	pIC50
banyu (I)	Inverse agonist	8.5	pKi
lazucirnon	Antagonist	8.49	pKi
RO320-2947/001	Antagonist	8.4	pIC50
SB328437	Antagonist	8.4	pKi
RO330-0802/001	Antagonist	8.3	pIC50
[125I]CCL11 (human)	Antagonist	8.3	pKd
[3H]banyu (I)	Inverse agonist	8.3	pKd
Met-Ckβ7	Antagonist	8.2	pIC50
AZD3778	Antagonist	8.2	pKi
BMS compound 87b	Antagonist	8.1	pKi
YM-355179	Antagonist	8.1	pIC50
GW766994	Antagonist	8.0	pIC50
CCL2	Full agonist	7.8	pKi
RO116-4875/608	Antagonist	7.2	pIC50
UCB35625	Antagonist	7.03	pIC50

Binding affinities (BindingDB)

61 measured of 61 human assays (61 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-[6-methyl-4-(pyrrolidine-1-carbonyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	KI	0.9 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N-ethyl-N,6-dimethylpyridine-4-carboxamide	KI	1.7 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,6-dimethyl-N-propan-2-ylpyridine-4-carboxamide	KI	2.3 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-6-cyclopropyl-N,N-dimethylpyridine-4-carboxamide	KI	2.3 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	3.2 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N-(cyclopropylmethyl)-6-methylpyridine-4-carboxamide	KI	3.5 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
N-butan-2-yl-2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-6-methylpyridine-4-carboxamide	KI	4 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N-dimethyl-6-propan-2-ylpyridine-4-carboxamide	KI	4.1 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N-cyclobutyl-6-methylpyridine-4-carboxamide	KI	4.2 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-6-methyl-N-(2-methylpropyl)pyridine-4-carboxamide	KI	4.3 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N-(2,2-difluoroethyl)-6-methylpyridine-4-carboxamide	KI	4.6 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxo-N-[4-(pyrrolidine-1-carbonyl)-2-pyridinyl]pyrrolidine-2-carboxamide	KI	4.7 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
CHEMBL2058071	IC50	4.9 nM
N-butan-2-yl-2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,6-dimethylpyridine-4-carboxamide	KI	5.2 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-bromo-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	5.8 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-[6-methyl-4-(morpholine-4-carbonyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	KI	6 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
(2R)-N-[4-(azetidine-1-carbonyl)-6-methyl-2-pyridinyl]-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carboxamide	KI	6.8 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-ethylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	7.9 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-6-ethynyl-N,N-dimethylpyridine-4-carboxamide	KI	7.9 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
CHEMBL2057751	IC50	8 nM
1-{(S)-1-[3-(4-Chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-8-ylmethyl]-2-hydroxy-propyl}-3-(3,4,5-trimethoxy-phenyl)-urea	IC50	8.2 nM
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-6-ethyl-N,N-dimethylpyridine-4-carboxamide	KI	8.3 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N-dimethylpyridine-4-carboxamide	KI	8.5 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,6-dimethylpyridine-4-carboxamide	KI	10.4 nM	US-10213421
1-{(R)-2-[3-(4-Chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-1-methyl-ethyl}-3-(3,4,5-trimethoxy-phenyl)-urea	IC50	11 nM
1-{(S)-1-[3-(4-Chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-8-ylmethyl]-2-hydroxy-propyl}-3-(3-methanesulfonyl-phenyl)-urea	IC50	12 nM
2-[[(2R)-1-[1-[(3,4-dichlorophenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	17.8 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-[4-(morpholine-4-carbonyl)-2-pyridinyl]-5-oxopyrrolidine-2-carboxamide	KI	19.1 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
CHEMBL258996	IC50	20 nM
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N-methylpyridine-4-carboxamide	KI	23.4 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
CHEMBL2058073	IC50	30 nM
CHEMBL2058072	IC50	31 nM
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-(4-methoxy-2-pyridinyl)-5-oxopyrrolidine-2-carboxamide	KI	46.5 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
CHEMBL2057755	IC50	51 nM
2-[[(2R)-1-[1-[(4-chloro-3,5-dimethylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	61.3 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
CHEMBL2057759	IC50	63 nM
1-{(R)-2-[3-(4-Chloro-benzyl)-8-aza-bicyclo[3.2.1]oct-8-yl]-1-methyl-ethyl}-3-(3-methanesulfonyl-phenyl)-urea	IC50	65 nM
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-(4-methyl-2-pyridinyl)-5-oxopyrrolidine-2-carboxamide	KI	67.5 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-(6-methyl-2-pyridinyl)-5-oxopyrrolidine-2-carboxamide	KI	69.6 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[(4-fluoro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	70.3 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
6-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N-methylpyridine-2-carboxamide	KI	72 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
2-[[(2R)-1-[1-[[4-chloro-3-(trifluoromethyl)phenyl]methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-N,N,6-trimethylpyridine-4-carboxamide	KI	87.2 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
1-Adamantan-1-yl-3-{3-[4-(4-fluoro-benzyl)-piperidin-1-yl]-propyl}-urea	IC50	90 nM
(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-N-(4-ethyl-2-pyridinyl)-5-oxopyrrolidine-2-carboxamide	KI	197 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
1-((1R,2S)-3-{adamantan-1-ylmethyl-[3-(4-fluoro-phenyl)-propyl]-amino}-2-hydroxy-1-methyl-propyl)-3-[3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-urea	IC50	211 nM
N-{(3-exo)-8-[(6-Fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-(1H-imidazol-1-yl)benzamide	IC50	217 nM
N-{(3-exo)-8-[(6-Fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-(1H-pyrrol-1-yl)benzamide	IC50	221 nM
2-[[(2R)-1-[1-[(4-chloro-3-methylphenyl)methyl]piperidin-4-yl]-5-oxopyrrolidine-2-carbonyl]amino]-6-methoxy-N,N-dimethylpyridine-4-carboxamide	KI	232 nM	US-8742115: Co-crystals and salts of CCR3-inhibitors
N-{(3-exo)-8-[(6-Fluoro-2-naphthyl)methyl]-8-azabicyclo[3.2.1]oct-3-yl}-2-piperidin-1-ylbenzamide	IC50	279 nM
CHEMBL2057752	IC50	310 nM

ChEMBL bioactivities

1305 potent at pChembl≥5 of 1334 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL363840
10.96	IC50	0.011	nM	CHEMBL257074
10.89	IC50	0.013	nM	CHEMBL254930
10.89	IC50	0.013	nM	CHEMBL437031
10.82	IC50	0.015	nM	CHEMBL365820
10.80	IC50	0.016	nM	CHEMBL2113074
10.70	IC50	0.02	nM	CHEMBL257293
10.70	IC50	0.02	nM	CHEMBL270582
10.70	IC50	0.02	nM	CHEMBL427728
10.68	IC50	0.021	nM	CHEMBL404122
10.52	IC50	0.03	nM	CHEMBL195433
10.47	IC50	0.034	nM	CHEMBL250689
10.42	IC50	0.038	nM	CHEMBL399495
10.41	IC50	0.039	nM	CHEMBL250689
10.40	IC50	0.04	nM	CHEMBL399495
10.38	IC50	0.042	nM	CHEMBL382108
10.35	IC50	0.045	nM	CHEMBL2113077
10.30	IC50	0.05	nM	CHEMBL401879
10.30	IC50	0.05	nM	CHEMBL402983
10.22	IC50	0.06	nM	CHEMBL3706810
10.22	IC50	0.06	nM	CHEMBL256068
10.19	IC50	0.064	nM	CHEMBL258156
10.17	IC50	0.068	nM	CHEMBL249854
10.12	IC50	0.075	nM	CHEMBL251079
10.05	IC50	0.09	nM	CHEMBL195790
10.00	IC50	0.1	nM	CHEMBL195555
10.00	IC50	0.1	nM	CHEMBL250056
10.00	IC50	0.1	nM	CHEMBL429846
10.00	IC50	0.1	nM	CHEMBL270146
10.00	IC50	0.1	nM	CHEMBL270147
9.92	IC50	0.12	nM	CHEMBL518571
9.82	IC50	0.15	nM	CHEMBL505914
9.74	IC50	0.18	nM	CHEMBL461445
9.70	Ki	0.1995	nM	CHEMBL2158790
9.70	IC50	0.2	nM	CHEMBL254095
9.70	IC50	0.2	nM	CHEMBL398548
9.70	IC50	0.2	nM	CHEMBL251837
9.70	IC50	0.2	nM	CHEMBL428071
9.70	IC50	0.2	nM	CHEMBL255398
9.64	IC50	0.23	nM	CHEMBL464902
9.60	IC50	0.25	nM	CHEMBL277131
9.52	IC50	0.3	nM	CHEMBL2113077
9.52	IC50	0.3	nM	CHEMBL399495
9.52	IC50	0.3	nM	CHEMBL437396
9.52	IC50	0.3	nM	CHEMBL252035
9.52	IC50	0.3	nM	CHEMBL429323
9.52	IC50	0.304	nM	CHEMBL272068
9.52	IC50	0.3	nM	CHEMBL429604
9.50	Ki	0.3162	nM	CHEMBL2207654
9.44	IC50	0.364	nM	CHEMBL370082

PubChem BioAssay actives

1253 with measured affinity, of 1636 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
1-[(2R,3S)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-3-hydroxybutan-2-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	313941: Antagonist activity at human CCR3 receptor assessed as inhibition of chemotaxis in eosinophil	ic50	<0.0001	uM
1-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R,3S)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-3-hydroxybutan-2-yl]urea	313941: Antagonist activity at human CCR3 receptor assessed as inhibition of chemotaxis in eosinophil	ic50	<0.0001	uM
1-[3,5-bis(1-methyltetrazol-5-yl)phenyl]-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-(3-acetylphenyl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-(1H-indol-5-yl)urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-(3-acetyl-4-fluorophenyl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-(3,5-diacetylphenyl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-(1H-indazol-5-yl)urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	<0.0001	uM
1-[(2R,3S)-4-[cyclopropylmethyl-[3-(4-fluorophenyl)propyl]amino]-3-hydroxybutan-2-yl]-3-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]urea	313941: Antagonist activity at human CCR3 receptor assessed as inhibition of chemotaxis in eosinophil	ic50	<0.0001	uM
1-[(2R,3S)-4-[ethyl-[3-(4-fluorophenyl)propyl]amino]-3-hydroxybutan-2-yl]-3-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]urea	313941: Antagonist activity at human CCR3 receptor assessed as inhibition of chemotaxis in eosinophil	ic50	<0.0001	uM
1-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]-3-[3-(1-methyltetrazol-5-yl)-5-propan-2-ylphenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]-3-[3-methyl-5-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]-3-[3-(1-methyltetrazol-5-yl)-5-propan-2-ylphenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]-3-[3-methyl-5-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[(2R,4S)-4-(dimethylamino)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]-3-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[(3R)-1-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]hexan-3-yl]-3-[3-(2-hydroxypropan-2-yl)-5-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-[3-acetyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	<0.0001	uM
1-(4-chloro-1,3-benzothiazol-2-yl)-3-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	0.0001	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-(1H-indazol-6-yl)urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	0.0001	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-[3-(5-methyltetrazol-1-yl)phenyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	0.0001	uM
1-[(3S,4S)-1-acetyl-4-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]piperidin-3-yl]-3-(5-acetyl-4-methyl-1,3-thiazol-2-yl)urea	310949: Antagonist activity at CCR3 assessed as eotaxin-induced chemotaxis in human eosinophils	ic50	0.0001	uM
1-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-[(3S,4R)-3-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]piperidin-4-yl]urea	310949: Antagonist activity at CCR3 assessed as eotaxin-induced chemotaxis in human eosinophils	ic50	0.0001	uM
1-(5-acetyl-4-methyl-1,3-thiazol-2-yl)-3-[(3S,4S)-4-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]piperidin-3-yl]urea	310949: Antagonist activity at CCR3 assessed as eotaxin-induced chemotaxis in human eosinophils	ic50	0.0001	uM
1-[3,5-bis(1,2-oxazol-3-yl)phenyl]-3-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
2-[3-[[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]carbamoylamino]-5-(1-methyltetrazol-5-yl)phenyl]-2-methylpropanoic acid	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-[3,5-di(pyrazol-1-yl)phenyl]-3-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-[3-bromo-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]pentan-2-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-(3,5-diacetylphenyl)-3-[(2R,4R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-hydroxybutan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-[(3R)-1-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]pentan-3-yl]-3-[3-(2-hydroxypropan-2-yl)-5-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-[3,5-di(pyrazol-1-yl)phenyl]-3-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0001	uM
1-[6-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-3,5-dimethyl-2-oxo-1,3-oxazinan-5-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	412221: Binding affinity to CCR3 receptor	ic50	0.0001	uM
1-[6-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-3,5-dimethyl-2-oxo-1,3-oxazinan-5-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea;hydrochloride	412221: Binding affinity to CCR3 receptor	ic50	0.0001	uM
1-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]-4-oxobutan-2-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0002	uM
1-[(2R,3S)-4-[ethyl-[3-(4-fluorophenyl)propyl]amino]-3-hydroxybutan-2-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	313937: Displacement of [125I] eotaxin from human CCR3 receptor in CHO cells	ic50	0.0002	uM
1-[(2R,3S)-4-[3-(4-fluorophenyl)propyl-propylamino]-3-hydroxybutan-2-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	313937: Displacement of [125I] eotaxin from human CCR3 receptor in CHO cells	ic50	0.0002	uM
1-[(2R,3S)-4-[ethyl-[(2S)-4-(4-fluorophenyl)butan-2-yl]amino]-3-hydroxybutan-2-yl]-3-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]urea	313937: Displacement of [125I] eotaxin from human CCR3 receptor in CHO cells	ic50	0.0002	uM
1-(3,5-diacetylphenyl)-3-[(2R)-4-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]butan-2-yl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0002	uM
1-[(5R,6S)-6-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]-3-methyl-2-oxo-1,3-oxazinan-5-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	412221: Binding affinity to CCR3 receptor	ic50	0.0002	uM
1-[6-[[ethyl-[3-(4-fluorophenyl)propyl]amino]methyl]-3,5-dimethyl-2-oxo-1,3-oxazinan-5-yl]-3-[3-(1-methyltetrazol-5-yl)phenyl]urea	412221: Binding affinity to CCR3 receptor	ic50	0.0002	uM
(2S)-2-[4-[[4-(3,4-dichloro-2-methylphenoxy)piperidin-1-yl]methyl]piperidin-1-yl]-3-(4-fluorophenyl)-2-methylpropanoic acid	695625: Binding affinity to human CCR3 expressed in CHOK1 cells by radioligand displacement assay	ki	0.0002	uM
1-[(1R,2S)-2-[[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]methyl]cyclohexyl]-3-[4-(1-methyltetrazol-5-yl)phenyl]urea	242778: Inhibition of eotaxin-induced chemotaxis of human eosinophils	ic50	0.0003	uM
1-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R,3S)-4-[3-(4-fluorophenyl)propylamino]-3-hydroxybutan-2-yl]urea	313937: Displacement of [125I] eotaxin from human CCR3 receptor in CHO cells	ic50	0.0003	uM
1-[3-ethyl-5-(1-methyltetrazol-5-yl)phenyl]-3-[(2R,3S)-4-[3-(4-fluorophenyl)propyl-methylamino]-3-hydroxybutan-2-yl]urea	313937: Displacement of [125I] eotaxin from human CCR3 receptor in CHO cells	ic50	0.0003	uM
2-[3-[3-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]propylcarbamoylamino]-5-(1-methyltetrazol-5-yl)phenyl]-2-methylpropanoic acid	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0003	uM
1-[3-[(3S)-3-[(4-fluorophenyl)methyl]piperidin-1-yl]propyl]-3-[3-(1-methyltetrazol-5-yl)-5-propan-2-ylphenyl]urea	317908: Antagonist activity at human CCR3 receptor in human eosinophil assessed as inhibition of eotaxin-induced chemotaxis	ic50	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aspirin	increases expression, affects response to substance	3
Ozone	affects expression, increases abundance, affects cotreatment, increases expression	2
Plant Extracts	decreases reaction, increases abundance, decreases expression	2
Tretinoin	increases expression	2
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
triphenyl phosphate	affects expression	1
proanthocyanidin	decreases expression	1
oxophenylarsine	decreases expression, decreases reaction	1
zinc sulfide	affects cotreatment, decreases expression	1
1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione	affects binding, decreases reaction, increases activity	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
SB 203580	affects binding, decreases reaction, increases activity	1
antileukinate	affects binding, decreases reaction	1
SB 297006	affects binding, decreases reaction, increases activity	1
lipopolysaccharide, E. coli O26-B6	decreases expression	1
Aripiprazole	affects cotreatment, increases expression	1
Wortmannin	decreases expression, decreases reaction	1
Alitretinoin	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects expression	1
Benzo(a)pyrene	increases methylation	1
Butyrates	increases expression	1
Cadmium	affects cotreatment, decreases expression	1
Cannabinoids	decreases expression, decreases reaction, increases abundance	1
Dexamethasone	decreases expression	1
Emodin	affects binding, decreases reaction, increases activity	1
Indomethacin	decreases expression	1
Selenium	affects cotreatment, decreases expression	1

ChEMBL screening assays

175 unique, capped per target: 107 binding, 68 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001499	Binding	Inhibition of CCR3 at 10 uM	Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. — Bioorg Med Chem Lett
CHEMBL1055679	Functional	Antagonist activity at human CCR3 expressed in mouse B300-19 cells assessed as inhibition of eotaxin-induced calcium flux	Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists. — Bioorg Med Chem

Cellosaurus cell lines

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

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

Cellosaurus	Name	Category	Sex
CVCL_1D96	HOS-CD4-CCR3	Cancer cell line	Female
CVCL_1E08	GHOST(3).R3/X4/R5	Cancer cell line	Female
CVCL_1E14	3T3.T4.CCR3	Transformed cell line	Male
CVCL_1R20	NP-2/CCR3	Cancer cell line	Male
CVCL_1R26	NP-2/CD4/CCR3	Cancer cell line	Male
CVCL_6337	AML14.3D10/CCCKR3 Clone 16	Cancer cell line	Male
CVCL_B8CM	Abcam HCT 116 CCR3 KO	Cancer cell line	Male
CVCL_B9EV	Abcam A-549 CCR3 KO	Cancer cell line	Male
CVCL_D2E4	Abcam MCF-7 CCR3 KO	Cancer cell line	Female
CVCL_E4JZ	HEK293 CCR3	Transformed cell line	Female

Clinical trials (associated diseases)

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