CCR2

Summary

CCR2 (C-C motif chemokine receptor 2, HGNC:1603) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor type 2 (P41597). Key functional receptor for CCL2 but can also bind CCL7, and CCL12.

The protein encoded by this gene is a receptor for monocyte chemoattractant protein-1, a chemokine which specifically mediates monocyte chemotaxis. Monocyte chemoattractant protein-1 is involved in monocyte infiltration in inflammatory diseases such as rheumatoid arthritis as well as in the inflammatory response against tumors. The encoded protein mediates agonist-dependent calcium mobilization and inhibition of adenylyl cyclase. This protein can also be a coreceptor with CD4 for HIV-1 infection. This gene is located in the chemokine receptor gene cluster region of chromosome 3.

Source: NCBI Gene 729230 — RefSeq curated summary.

At a glance

• GWAS associations: 19
• Clinical variants (ClinVar): 60 total — 5 pathogenic
• Phenotypes (HPO): 4
• Druggable target: yes — 17 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001123396

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1603
Approved symbol	CCR2
Name	C-C motif chemokine receptor 2
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CC-CKR-2, CKR2, MCP-1-R, CD192, FLJ78302
Ensembl gene	ENSG00000121807
Ensembl biotype	protein_coding
OMIM	601267
Entrez	729230

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000400888, ENST00000421659, ENST00000445132, ENST00000465202, ENST00000908302, ENST00000963442

RefSeq mRNA: 2 — MANE Select: NM_001123396 NM_001123041, NM_001123396

CCDS: CCDS43078, CCDS46813

Canonical transcript exons

ENST00000445132 — 2 exons

Exon	Start	End
ENSE00001623822	46357477	46360940
ENSE00001839982	46354111	46354177

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 97.73.

FANTOM5 (CAGE): breadth broad, TPM avg 3.0017 / max 264.1607, expressed in 213 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36448	1.7934	164
36443	0.5969	107
36449	0.1850	66
36447	0.1205	57
36445	0.0739	26
36446	0.0717	31
36444	0.0695	29
36442	0.0489	24
36441	0.0419	23

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	97.73	gold quality
mononuclear cell	CL:0000842	97.51	gold quality
leukocyte	CL:0000738	97.40	gold quality
granulocyte	CL:0000094	94.01	gold quality
blood	UBERON:0000178	89.47	gold quality
bone marrow cell	CL:0002092	87.16	gold quality
vermiform appendix	UBERON:0001154	83.29	gold quality
spleen	UBERON:0002106	81.01	gold quality
lymph node	UBERON:0000029	80.29	gold quality
trabecular bone tissue	UBERON:0002483	78.71	gold quality
bone marrow	UBERON:0002371	78.04	gold quality
caecum	UBERON:0001153	76.12	gold quality
parietal pleura	UBERON:0002400	75.31	gold quality
rectum	UBERON:0001052	74.40	gold quality
pleura	UBERON:0000977	73.54	gold quality
gall bladder	UBERON:0002110	71.80	gold quality
smooth muscle tissue	UBERON:0001135	71.23	gold quality
right coronary artery	UBERON:0001625	70.72	gold quality
duodenum	UBERON:0002114	70.49	gold quality
mucosa of transverse colon	UBERON:0004991	70.29	gold quality
visceral pleura	UBERON:0002401	70.19	gold quality
ileal mucosa	UBERON:0000331	69.52	gold quality
upper leg skin	UBERON:0004262	69.32	gold quality
palpebral conjunctiva	UBERON:0001812	68.19	gold quality
upper lobe of left lung	UBERON:0008952	67.27	gold quality
skin of hip	UBERON:0001554	67.26	gold quality
upper lobe of lung	UBERON:0008948	66.87	gold quality
small intestine Peyer’s patch	UBERON:0003454	66.21	gold quality
small intestine	UBERON:0002108	66.15	gold quality
lung	UBERON:0002048	65.78	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9067	yes	12.89
E-ANND-3	yes	8.89
E-MTAB-9801	yes	5.82
E-GEOD-110499	no	644.58

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AR, CEBPA, CEBPG, CREB3, FOXC1, FOXM1, NFKB1, NR3C1, PPARG, RELA, ZNF160

Literature-anchored findings (GeneRIF, showing 40)

• Association of CCR2 genotype with disease progression of HIV infection (PMID:11709782)
• genotypes and their relative contribution to human immunodeficiency virus type 1 (HIV-1) seroconversion, early HIV-1 RNA concentration in plasma, and later disease progression (PMID:11752157)
• CCR2 641 allele homozygosity implicated in natural resistance to HIV-1 transmission through heterosexual contact (PMID:11873083)
• The frequencies of CCR2 mutation associated with the development of clinical symptoms upon infection with human immunodeficiency virus type 1 (HIV-1) were determined in a cohort of individuals from Moscow. (PMID:11898620)
• 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 CCR2B in aiway epithelial cells after injury enhances cell migration and proliferation (PMID:12078856)
• May be a new candidate for a susceptibility locus for bone mass in middle-aged men and postmenopausal women (PMID:12079277)
• Electrostatic potential maps of human and primate CCR2b all display the dipolar characteristics of CCR2b with the negative pole located in the extracellular part and a strong positive pole in the cytoplasmic part. (PMID:12192431)
• Results show that high ambient glucose does not affect mesangial monocyte chemoattractant protein-1 release and decreases its chemokine receptor 2 (CCR2) receptor expression. (PMID:12399623)
• C-C chemokine receptor 2 and C-C chemokine receptor 5 genotypes in patients treated for chronic hepatitis C virus infection. (PMID:12403355)
• Val64Ile polymorphism in the C-C chemokine receptor 2 is associated with reduced coronary artery calcification. (PMID:12426226)
• Polymorphism is associated with myocardial infarct. (PMID:12469616)
• The specific distribution and regulation of chemokine receptors CXCR1, CXCR4, CCR5, and CCR2b in endometrial epithelium and blastocyst suggest a role for these receptors in the apposition and adhesion phases of human implantation. (PMID:12651900)
• CCR2 genotype seems to predispose patients for myocardial infarction before the age of 65 years; the higher prevalence of heart failure in gene carriers with the rare alle might be a consequence of myocardial infarction (PMID:12719858)
• activation of CCR5 and CCR2 is induced by conformational changes in the conserved TXP motif in transmembrane helix 2 (PMID:12837756)
• females with the VI genotype were seven times more prone to suffer from myocardial infarction before 50 years than those with the VV genotype (PMID:12853162)
• The calculation of the congruence revealed that 92.0% of individuals exhibited the same genotype for both CCR2-64I and CCR5-59653T polymorphisms. Our results confirm that linkage between CCR5-59653T and CCR2-64I alleles is not absolute. (PMID:12884524)
• Polymorphisms of CCR2 and CCR5 do not seem to be involved in susceptibility to systemic lupus erythematosis (PMID:12913933)
• Angiotensin II significantly stimulated superoxide formation in monocytes, as well as the chemotactic response to MCP-1 with the increased expression of monocyte chemoattractant protein 1 receptor determined by RT-PCR and western blotting analysis (PMID:13678532)
• A PCR-based genotyping method was used to determine the genetic variation at the CCR5 gene and an automated real-time Pyrosequencing technology was employed for the analysis of G right curved arrow A point mutation at the CCR2 gene (PMID:14533004)
• The presence of the CCR2-64I allele in a Japanese population seems to provide protection against the development of multiple sclerosis. (PMID:14644039)
• Our findings suggest a limited role for CCL2/CCR2 in early active multiple sclerosis (PMID:15257681)
• A decreased frequency and an absence of homozygous for the polymorphism CCR2-64I were found. (PMID:15465089)
• The impact of CCR2 on neuropathogenesis may involve alterations in inflammatory responses within the CNS rather than a direct impact on viral entry or replication. (PMID:15579296)
• Did not support previous findings of an association between CCR2 gene variability and the risk of sarcoidosis; however, linkage disequilibrium showed positive results and suggests susceptibility gene in surrounding chromosomal region. (PMID:15750046)
• Frequency distribution of CCR2-64I mutations in Brazilian Amazon region (PMID:15754978)
• subclinical clotting activation may cause an increased CCR2 gene and protein expression on uremic peripheral blood mononuclear cells, contributing to hemodialysis-related chronic microinflammation (PMID:15976001)
• These data suggest that the regulation of the CCL2 and CXCL10 expression exhibit significant differences in their mechanisms, and also demonstrate that the alveolar epithelium contributes to the cytokine milieu of the lung. (PMID:16033640)
• Genetic variation in CC-chemokine receptor-2 (CCR2) and -5 (CCR5), and their common haplotypes, acting through inflammatory responses, may affect atherosclerosis and risk of coronary heart disease (CHD). (PMID:16055130)
• The results indicate that pulmonary CCR2+ T cells and MCP-1 contribute to the pathogenesis of pediatric ILD and might provide a novel target for therapeutic strategies. (PMID:16095529)
• potential autocrine regulation of key profibrotic properties via a CCL2/CCR2 loop in early-stage diffuse cutaneous systemic sclerosis (PMID:16320328)
• These data suggest that fibrogenic processes in Mo regulated by MCP-1/CCR2 may be novel, therapeutic targets for combating organ fibrosis. (PMID:16415174)
• results of the present study provide no evidence that either CCR5-Delta32 or CCR2-64I is associated with hypertension (PMID:16461193)
• the risk of acute rejection in renal transplantation may be associated with genetic variation in the chemokine receptor genes CCR5-59029 and CCR2V641 in Turkey (PMID:16598837)
• Our data suggest that elevated serum MCP-1 levels and increased monocyte CCR2, CD36, CD68 expression correlate with poor blood glucose control and potentially contribute to increased recruitment of monocytes to the vessel wall in diabetes mellitus. (PMID:16631114)
• Double immunofluorescense staining demonstrated that cellular sources of MCP-1/CCL2 and IP-10/CXCL10 were hypertrophic astrocytes and that both astrocytes and microglia/macrophages expressed CCR2 and CXCR3. (PMID:16733654)
• The mRNA expressions of CCR2 of all post-kidney transplant patients were significantly higher than controls. (PMID:16781696)
• In atherogenesis, oxidized lipid-driven activation of macrophage PPARgamma in the intima may result in a proadhesive chemokine receptor switch-CCR2 off. (PMID:16908772)
• evaluated the possible relation between CCR2 and CCR5 alleles and blood pressure (BP) levels in hypertensive (PMID:17060059)
• Results suggest that CCR2 may contribute to prostate cancer development. (PMID:17216598)

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	Ccr2	ENSMUSG00000049103
rattus_norvegicus	Ccr2	ENSRNOG00000063127

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), 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), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor type 2 — P41597 (reviewed: P41597)

Alternative names: Monocyte chemoattractant protein 1 receptor

All UniProt accessions (2): E9PH76, P41597

UniProt curated annotations — full annotation on UniProt →

Function. Key functional receptor for CCL2 but can also bind CCL7, and CCL12. Also transduces signaling mediated by CCL13. Its binding with CCL2 on monocytes and macrophages mediates chemotaxis and migration induction through the activation of the PI3K cascade, the small G protein Rac and lamellipodium protrusion. Also acts as a receptor for the beta-defensin DEFB106A/DEFB106B. Regulates the expression of T-cell inflammatory cytokines and T-cell differentiation, promoting the differentiation of T-cells into T-helper 17 cells (Th17) during inflammation. Facilitates the export of mature thymocytes by enhancing directional movement of thymocytes to sphingosine-1-phosphate stimulation and up-regulation of S1P1R expression; signals through the JAK-STAT pathway to regulate FOXO1 activity leading to an increased expression of S1P1R. Plays an important role in mediating peripheral nerve injury-induced neuropathic pain. Increases NMDA-mediated synaptic transmission in both dopamine D1 and D2 receptor-containing neurons, which may be caused by MAPK/ERK-dependent phosphorylation of GRIN2B/NMDAR2B. Mediates the recruitment of macrophages and monocytes to the injury site following brain injury. (Microbial infection) Alternative coreceptor with CD4 for HIV-1 infection.

Subunit / interactions. Interacts with ARRB1. Interacts (via extracellular N-terminal region) with beta-defensin DEFB106A/DEFB106B; this interaction may preferentially require specific tyrosine sulfation on CCR2. Interacts with NUP85; the interaction is required for CCR2 clusters formation on the cell membrane and CCR2 signaling. Interacts with GNAI1. (Microbial infection) Binds to HIV-1 Tat. (Microbial infection) Interacts with Kaposi virus protein vCCL2.

Subcellular location. Cell membrane.

Tissue specificity. Expressed by monocytes and IL2-activated NK cells. Abundantly expressed on CD14+/CD16- monocytes and weakly on CD14+/CD16+ monocytes, type 2 dendritic cells (DCs) and plasmacytoid DCs (at protein level).

Post-translational modifications. N-glycosylated. Sulfation increases the affinity for both monomeric and dimeric CCL2 with stronger binding to the monomeric form. Binding of sulfated CCR2 to CCL2 promotes conversion of CCL2 from dimer to monomer.

Disease relevance. Polycystic lung disease (PCLUD) [MIM:219600] An autosomal recessive disease characterized by pulmonary alveolar proteinosis, marked peribronchovascular and parenchymal lymphocytosis, peribronchiolar pulmonary fibrosis, progressive diffuse parenchymal lung cyst formation and enlargement, progressive obstructive airflow limitation, and recurrent secondary infections. Additional features may include digital clubbing, allergies, and atopic dermatitis. The disease is caused by variants affecting the gene represented in this entry.

Induction. Up-regulated by CREB3. In NK cells, induced by IL2.

Polymorphism. Variations in CCR2 are associated with relative resistance to immunodeficiency virus type 1 (resistance to HIV-1) [MIM:609423].

Miscellaneous. Mutagenesis of Leu-316 to Thr as well as Phe-320 to Asp decrease interaction with NUP85.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P41597-1	A	yes
P41597-2	B

RefSeq proteins (2): NP_001116513, NP_001116868* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR002237	Chemokine_CCR2	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (51 total): helix 14, sequence variant 10, topological domain 8, transmembrane region 7, turn 3, modified residue 2, strand 2, chain 1, region of interest 1, glycosylation site 1, disulfide bond 1, splice variant 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
7P8X	X-RAY DIFFRACTION	1.4
6GPX	X-RAY DIFFRACTION	2.7
5T1A	X-RAY DIFFRACTION	2.81
7XA3	ELECTRON MICROSCOPY	2.9
6GPS	X-RAY DIFFRACTION	3.3
2MLO	SOLUTION NMR
2MLQ	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P41597-F1	78.28	0.53

Antibody-complex structures (SAbDab): 1 — 7XA3

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): 26, 139

Disulfide bonds (1): 113–190

Glycosylation sites (1): 14

Function

Pathways and Gene Ontology

Reactome pathways

16 pathways

ID	Pathway
R-HSA-1461957	Beta defensins
R-HSA-380108	Chemokine receptors bind chemokines
R-HSA-418594	G alpha (i) signalling events
R-HSA-6783783	Interleukin-10 signaling
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-1461973	Defensins
R-HSA-162582	Signal Transduction
R-HSA-168249	Innate Immune System
R-HSA-168256	Immune System
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-449147	Signaling by Interleukins
R-HSA-500792	GPCR ligand binding
R-HSA-6803157	Antimicrobial peptides

MSigDB gene sets: 590 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GOBP_POSITIVE_REGULATION_OF_SYNAPTIC_TRANSMISSION_GLUTAMATERGIC, GOBP_REGULATION_OF_LEUKOCYTE_PROLIFERATION, ZHAN_LATE_DIFFERENTIATION_GENES_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_MYELOID_CELL_HOMEOSTASIS, GOBP_REGULATION_OF_T_CELL_CHEMOTAXIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM

GO Biological Process (60): blood vessel remodeling (GO:0001974), dendritic cell chemotaxis (GO:0002407), monocyte chemotaxis (GO:0002548), regulation of T cell cytokine production (GO:0002724), positive regulation of T-helper 1 type immune response (GO:0002827), negative regulation of type 2 immune response (GO:0002829), intracellular calcium ion homeostasis (GO:0006874), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), humoral immune response (GO:0006959), cellular defense response (GO:0006968), negative regulation of adenylate cyclase activity (GO:0007194), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), response to wounding (GO:0009611), regulation of vascular endothelial growth factor production (GO:0010574), positive regulation of T cell chemotaxis (GO:0010820), negative regulation of angiogenesis (GO:0016525), cytokine-mediated signaling pathway (GO:0019221), sensory perception of pain (GO:0019233), calcium-mediated signaling (GO:0019722), cellular homeostasis (GO:0019725), hemopoiesis (GO:0030097), positive regulation of type II interferon production (GO:0032729), positive regulation of interleukin-2 production (GO:0032743), positive regulation of tumor necrosis factor production (GO:0032760), monocyte extravasation (GO:0035696), T-helper 17 cell chemotaxis (GO:0035705), negative regulation of eosinophil degranulation (GO:0043310), regulation of T cell differentiation (GO:0045580), positive regulation of alpha-beta T cell proliferation (GO:0046641), homeostasis of number of cells within a tissue (GO:0048873), regulation of inflammatory response (GO:0050727), positive regulation of inflammatory response (GO:0050729), positive regulation of T cell activation (GO:0050870), positive regulation of synaptic transmission, glutamatergic (GO:0051968), cell chemotaxis (GO:0060326), leukocyte adhesion to vascular endothelial cell (GO:0061756), chemokine-mediated signaling pathway (GO:0070098)

GO Molecular Function (11): chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), CCR2 chemokine receptor binding (GO:0031727), chemokine (C-C motif) ligand 2 binding (GO:0035715), chemokine (C-C motif) ligand 12 binding (GO:0035716), chemokine (C-C motif) ligand 7 binding (GO:0035717), identical protein binding (GO:0042802), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), cytokine binding (GO:0019955)

GO Cellular Component (9): fibrillar center (GO:0001650), cytoplasm (GO:0005737), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020), dendrite (GO:0030425), neuronal cell body (GO:0043025), perikaryon (GO:0043204), perinuclear region of cytoplasm (GO:0048471)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Immune System	2
Signaling by GPCR	2
Defensins	1
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signaling by Interleukins	1
Antimicrobial peptides	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1
Innate Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
C-C chemokine binding	4
leukocyte chemotaxis	2
defense response	2
chemokine binding	2
protein binding	2
tissue remodeling	1
dendritic cell migration	1
mononuclear cell migration	1
myeloid leukocyte migration	1
T cell cytokine production	1
regulation of T cell mediated immunity	1
regulation of cytokine production involved in immune response	1
positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains	1
regulation of T-helper 1 type immune response	1
T-helper 1 type immune response	1
regulation of type 2 immune response	1
type 2 immune response	1
negative regulation of immune response	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
immune response	1
adenylate cyclase activity	1
negative regulation of catalytic activity	1
regulation of adenylate cyclase activity	1
regulation of biological quality	1
cell surface receptor signaling pathway via STAT	1
response to stress	1
regulation of cytokine production	1
vascular endothelial growth factor production	1
T cell chemotaxis	1
regulation of T cell chemotaxis	1
positive regulation of lymphocyte chemotaxis	1
positive regulation of T cell migration	1
angiogenesis	1
regulation of angiogenesis	1

Protein interactions and networks

STRING

3236 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR2	CCL2	P13500	999
CCR2	CCL5	P13501	999
CCR2	CCL3	P10147	997
CCR2	CCL4	P13236	997
CCR2	CXCL12	P48061	997
CCR2	CCL7	P80098	997
CCR2	CXCL10	P02778	996
CCR2	CCL11	P50877	996
CCR2	CCL8	P78388	996
CCR2	CXCL8	P10145	995
CCR2	CX3CL1	P78423	994
CCR2	CCL13	Q99616	992
CCR2	CXCL1	P09341	988
CCR2	CCL20	P78556	988
CCR2	CCR5	P51681	983

IntAct

53 interactions, top by confidence:

A	B	Type	Score
MET	SRC	psi-mi:“MI:0914”(association)	0.790
SRC	MET	psi-mi:“MI:0914”(association)	0.790
CCR2	POTEE	psi-mi:“MI:0915”(physical association)	0.590
CCR2	SRC	psi-mi:“MI:2364”(proximity)	0.420
CCR2	MET	psi-mi:“MI:2364”(proximity)	0.420
CCR2	RAMP1	psi-mi:“MI:0915”(physical association)	0.400
RAMP2	CCR2	psi-mi:“MI:0915”(physical association)	0.400
CCR2	RAMP2	psi-mi:“MI:0915”(physical association)	0.400
RAMP3	CCR2	psi-mi:“MI:0915”(physical association)	0.400
ARL6IP5	CCR2	psi-mi:“MI:0915”(physical association)	0.370
APP	CCR2	psi-mi:“MI:0915”(physical association)	0.370
ATP2B1	CCR2	psi-mi:“MI:0915”(physical association)	0.370
B3GAT3	CCR2	psi-mi:“MI:0915”(physical association)	0.370
CACYBP	CCR2	psi-mi:“MI:0915”(physical association)	0.370
CD59	CCR2	psi-mi:“MI:0915”(physical association)	0.370
CD81	CCR2	psi-mi:“MI:0915”(physical association)	0.370
CDIP1	CCR2	psi-mi:“MI:0915”(physical association)	0.370
EMC10	CCR2	psi-mi:“MI:0915”(physical association)	0.370
CLPTM1	CCR2	psi-mi:“MI:0915”(physical association)	0.370
DMWD	CCR2	psi-mi:“MI:0915”(physical association)	0.370
S1PR5	CCR2	psi-mi:“MI:0915”(physical association)	0.370
ERGIC3	CCR2	psi-mi:“MI:0915”(physical association)	0.370
GPR161	CCR2	psi-mi:“MI:0915”(physical association)	0.370
WLS	CCR2	psi-mi:“MI:0915”(physical association)	0.370
GOT1	CCR2	psi-mi:“MI:0915”(physical association)	0.370
HMOX2	CCR2	psi-mi:“MI:0915”(physical association)	0.370
HERPUD1	CCR2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (42): POTEE (Affinity Capture-MS), ARL6IP5 (Two-hybrid), APP (Two-hybrid), ATP2B1 (Two-hybrid), B3GAT3 (Two-hybrid), CACYBP (Two-hybrid), CD59 (Two-hybrid), CD81 (Two-hybrid), CDIP1 (Two-hybrid), EMC10 (Two-hybrid), CLPTM1 (Two-hybrid), DMWD (Two-hybrid), S1PR5 (Two-hybrid), ERGIC3 (Two-hybrid), GPR161 (Two-hybrid)

ESM2 similar proteins: A1A5S3, A6QNL7, F5HDK1, F5HF62, O00421, O18982, O97663, O97664, P09703, P34997, P35350, P35351, P35374, P35411, P41597, P46090, P46091, P49238, P49685, P50052, P51675, P51676, P56412, P69332, P69333, P70658, Q01035, Q07FZ4, Q0II78, Q0VDU3, Q14330, Q28929, Q2KTE1, Q3T0E9, Q4R613, Q75ZH0, Q7ZXJ7, Q83207, Q89609, Q8K1Z6

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

4 interactions.

A	Effect	B	Mechanism
JAK2	“up-regulates activity”	CCR2	phosphorylation
CCL2	“up-regulates activity”	CCR2	binding
CCL3	“up-regulates activity”	CCR2	binding
CCR2	“up-regulates activity”	ERK1/2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 46 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
adenylate cyclase-activating G protein-coupled receptor signaling pathway	5	12.8×	7e-03
protein localization to plasma membrane	5	12.3×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	0
Uncertain significance	38
Likely benign	6
Benign	4

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
3061925	NM_001123396.4(CCR2):c.641_646del (p.Pro214_Leu215del)	Pathogenic
3061926	NM_001123396.4(CCR2):c.182T>G (p.Met61Arg)	Pathogenic
3061927	NM_001123396.4(CCR2):c.887C>A (p.Thr296Asn)	Pathogenic
3061928	NM_001123396.4(CCR2):c.59_60insAC (p.Thr21fs)	Pathogenic
3061929	NM_001123396.4(CCR2):c.356T>G (p.Leu119Arg)	Pathogenic

SpliceAI

270 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46357474:CAGAA:C	acceptor_loss	1.0000
3:46357475:A:AG	acceptor_gain	1.0000
3:46357475:A:C	acceptor_loss	1.0000
3:46357476:G:GA	acceptor_gain	1.0000
3:46357476:G:GT	acceptor_loss	1.0000
3:46357476:GA:G	acceptor_gain	1.0000
3:46357476:GAAC:G	acceptor_gain	1.0000
3:46357476:GAACA:G	acceptor_gain	1.0000
3:46358590:G:GT	donor_gain	1.0000
3:46354174:GCTG:G	donor_gain	0.9900
3:46357476:GAA:G	acceptor_gain	0.9900
3:46354178:G:GG	donor_gain	0.9800
3:46354178:GTGA:G	donor_loss	0.9800
3:46354179:T:G	donor_loss	0.9800
3:46359586:G:GG	donor_gain	0.9800
3:46354182:GTT:G	donor_gain	0.9700
3:46357468:T:TA	acceptor_gain	0.9500
3:46354173:AGCTG:A	donor_gain	0.9400
3:46354174:GCTGG:G	donor_gain	0.9400
3:46357473:A:AG	acceptor_gain	0.9400
3:46357474:C:G	acceptor_gain	0.9400
3:46354175:CTG:C	donor_gain	0.9200
3:46354859:TAG:T	acceptor_gain	0.9100
3:46354861:G:T	acceptor_gain	0.9100
3:46354182:G:C	donor_loss	0.9000
3:46354860:A:T	acceptor_gain	0.9000
3:46357477:AACAG:A	acceptor_gain	0.9000
3:46357478:ACAGA:A	acceptor_gain	0.9000
3:46359566:G:GT	donor_gain	0.9000
3:46354180:GAGTT:G	donor_gain	0.8900

AlphaMissense

2361 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:46358008:A:C	S161R	0.992
3:46358010:T:A	S161R	0.992
3:46358010:T:G	S161R	0.992
3:46358020:T:A	W165R	0.990
3:46358020:T:C	W165R	0.990
3:46357776:C:A	N83K	0.978
3:46357776:C:G	N83K	0.978
3:46358168:C:G	P214R	0.978
3:46357694:G:A	G56D	0.973
3:46358095:T:A	C190S	0.973
3:46358096:G:C	C190S	0.973
3:46357778:T:C	L84P	0.971
3:46358188:T:C	C221R	0.970
3:46358300:C:A	P258H	0.970
3:46357845:G:C	W106C	0.969
3:46357845:G:T	W106C	0.969
3:46357790:A:C	D88A	0.968
3:46357693:G:C	G56R	0.967
3:46357864:T:A	C113S	0.966
3:46357865:G:C	C113S	0.966
3:46358095:T:C	C190R	0.966
3:46358422:T:C	C299R	0.966
3:46358300:C:G	P258R	0.965
3:46357791:T:A	D88E	0.964
3:46357791:T:G	D88E	0.964
3:46358461:T:C	F312L	0.963
3:46358463:C:A	F312L	0.963
3:46358463:C:G	F312L	0.963
3:46358096:G:A	C190Y	0.962
3:46358168:C:A	P214Q	0.961

dbSNP variants (sampled 300 via entrez): RS1000130725 (3:46359261 T>C), RS1000199976 (3:46354122 G>C), RS1000908711 (3:46357393 T>C), RS1001267279 (3:46355467 G>C), RS1002239525 (3:46357433 C>T), RS1002676850 (3:46357087 C>G,T), RS1002841311 (3:46360350 C>T), RS1003016095 (3:46353615 TA>T,TAA), RS1003277914 (3:46354815 T>C), RS1003332112 (3:46356694 T>C,G), RS1003355536 (3:46353290 G>A), RS1003420442 (3:46352314 C>T), RS1003651330 (3:46358829 A>G), RS1004245965 (3:46360343 G>A), RS1004374514 (3:46356331 A>C)

Disease associations

OMIM: gene MIM:601267 | disease phenotypes: MIM:219600, MIM:609423

GenCC curated gene-disease

Mondo (2): cystic disease of lung (MONDO:0009060), susceptibility to HIV infection (MONDO:0004951)

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0002719	Recurrent infections
HP:0004876	Spontaneous neonatal pneumothorax
HP:0005948	Multiple pulmonary cysts

GWAS associations

19 associations (top):

Study	Trait	p-value
GCST000612_32	Celiac disease	3.000000e-17
GCST001762_308	Obesity-related traits	7.000000e-09
GCST002520_6	Celiac disease	4.000000e-08
GCST002665_3	Cerebrospinal fluid levels of Alzheimer’s disease-related proteins	2.000000e-13
GCST003043_90	Inflammatory bowel disease	4.000000e-08
GCST003045_10	Ulcerative colitis	9.000000e-10
GCST003045_18	Ulcerative colitis	1.000000e-08
GCST004133_35	Ulcerative colitis	2.000000e-06
GCST004608_73	Granulocyte percentage of myeloid white cells	2.000000e-25
GCST004609_109	Monocyte percentage of white cells	1.000000e-33
GCST004625_70	Monocyte count	1.000000e-11
GCST005523_14	Celiac disease	1.000000e-20
GCST005977_30	Monocyte count	7.000000e-14
GCST008489_15	Celiac disease	3.000000e-08
GCST009159_6	Blood protein levels	2.000000e-11
GCST010730_3	Rheumatoid arthritis	3.000000e-08
GCST90002393_236	Monocyte count	5.000000e-10
GCST90002393_237	Monocyte count	2.000000e-13
GCST90002394_243	Monocyte percentage of white cells	8.000000e-12

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0005091	monocyte count
EFO:0004747	protein measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C563237	Cystic Disease Of Lung (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4015 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

17 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 171,352 (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
CHEMBL11359	CISPLATIN	4
CHEMBL18442	PLERIXAFOR	4	11,099
CHEMBL193	NIFEDIPINE	4	74,353
CHEMBL633	AMIODARONE	4	29,704
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL2110727	CENICRIVIROC	3	2,137
CHEMBL2178578	VERCIRNON	3	349
CHEMBL38380	FASUDIL	3	11,953
CHEMBL2029422	PF-4136309	2
CHEMBL2178573	ILACIRNON	2	433
CHEMBL2204263	JNJ-41443532	2	32
CHEMBL3305901	MK-0812	2	27
CHEMBL397647	JNJ-17166864 CATION	2	36
CHEMBL4457723	BMS-741672	2	2
CHEMBL4594419	BMS-813160	2	57
CHEMBL541388	FASUDIL HYDROCHLORIDE	2	2,474
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 (31 total), top 25:

Ligand	Action	Affinity	Parameter
CCL2	Full agonist	10.2	pIC50
plozalizumab	Binding	9.72	pEC50
BMS-681	Antagonist	9.15	pIC50
vMIP-II	Antagonist	9.1	pIC50
BMS-741672	Antagonist	8.96	pIC50
compound 39 [PMID: 31742400]	Antagonist	8.8	pKi
MC148R	Antagonist	8.8	pIC50
CCL7	Full agonist	8.7	pIC50
CCL13	Full agonist	8.7	pIC50
CCL8	Full agonist	8.6	pIC50
AZD2423	Negative	8.59	pIC50
BMS-753426	Antagonist	8.57	pIC50
CCL26	Antagonist	8.5	pIC50
RS-136270	Antagonist	8.5	pIC50
INCB3284	Antagonist	8.43	pIC50
PF-04634817	Antagonist	8.43	pIC50
MK-0812	Antagonist	8.35	pIC50
ilacirnon	Antagonist	8.3	pIC50
INCB8761	Antagonist	8.28	pIC50
INCB3344	Antagonist	8.0	pIC50
CCL11	Partial agonist	7.7	pIC50
GSK Compound 34	Antagonist	7.6	pKi
TAK-779	Antagonist	7.2	pKi
vCCL4	Full agonist	7.1	pIC50
JNJ-27141491	Antagonist	7.02	pIC50

Binding affinities (BindingDB)

367 measured of 369 human assays (369 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
[5-[(3-methoxyoxan-4-yl)amino]-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[7-(trifluoromethyl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone	IC50	2 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
[5-(oxan-4-ylamino)-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[7-(trifluoromethyl)-3,4-dihydro-1H-isoquinolin-2-yl]methanone	IC50	3 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
[2-ethyl-5-[(3-methoxyoxan-4-yl)amino]-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	IC50	4 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
2-[1-[(E)-3-(3,5-difluorophenyl)prop-2-enoyl]piperidin-4-yl]-2-[[4-(1H-indol-3-yl)cyclohexyl]amino]acetamide	IC50	5 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
2-[[4-(1H-indol-3-yl)cyclohexyl]amino]-2-[1-[(E)-3-(3,4,5-trifluorophenyl)prop-2-enoyl]piperidin-4-yl]acetamide	IC50	5 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
[(2R,3aR,6aR)-2-[[(3S,4S)-3-ethyloxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	6 nM	US-8906911: Chemokine receptor antagonists
2-[(1S,4S)-5-[(2R,3aR,6aR)-2-(4-phenylpiperidin-1-yl)-2,3,4,5,6,6a-hexahydro-1H-pentalene-3a-carbonyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(trifluoromethyl)benzonitrile	KI	8 nM	US-8906911: Chemokine receptor antagonists
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methyloxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	10 nM	US-8906911: Chemokine receptor antagonists
N-{5-chloro-2-[(1H-imidazol-4-ylmethyl)thio]-phenyl}-1-benzofuran-2-sulfonamide	IC50	10 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[5-[(3-methoxyoxan-4-yl)amino]-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	IC50	11 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
N-[5-chloro-2-(methylsulfinyl)phenyl]-1-benzofuran-2-sulfonamide	IC50	11 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-[[(3S,4R)-3-methyloxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	12 nM	US-8906911: Chemokine receptor antagonists
[(2R,3aR,6aR)-2-[[(3S,4R)-3-ethyloxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	13 nM	US-8906911: Chemokine receptor antagonists
2-[1-[(E)-3-(3,5-difluorophenyl)prop-2-enoyl]piperidin-4-yl]-2-[[4-(1H-indol-3-yl)cyclohexyl]amino]acetamide	IC50	13 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
[5-[(3-methoxyoxan-4-yl)amino]-2-phenyl-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	IC50	14 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
4-chloro-N-[5-chloro-2-(methylsulfinyl)phenyl]-3-(trifluoromethyl)benzenesulfonamide	IC50	14 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-(4-phenylpiperidin-1-yl)-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	15 nM	US-8906911: Chemokine receptor antagonists
N-(2-{[(6-aminopyridin-2-yl)methyl]sulfonyl}-5-chlorophenyl)-1-benzofuran-2-sulfonamide	IC50	15 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[2-cyclopropyl-5-[(3-methoxyoxan-4-yl)amino]-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	IC50	16 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
2-[(1S,4S)-5-[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]-methylamino]-2,3,4,5,6,6a-hexahydro-1H-pentalene-3a-carbonyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(trifluoromethyl)benzonitrile	KI	16 nM	US-8906911: Chemokine receptor antagonists
N-{5-chloro-2-[(1H-pyrazol-3-ylmethyl)thio]phenyl}-1-benzofuran-2-sulfonamide	IC50	16 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-chloro-3-(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	17 nM	US-8906911: Chemokine receptor antagonists
N-{5-chloro-2-[(trifluoromethyl)sulfinyl]phenyl}-1-benzofuran-2-sulfonamide	IC50	19 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
CHEMBL1922813	IC50	19 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
2-[(1S,4S)-5-[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalene-3a-carbonyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]-4-(trifluoromethyl)benzonitrile	IC50	19.8 nM	US-8906911: Chemokine receptor antagonists
[5-[(3-methoxyoxan-4-yl)amino]-2-propyl-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	IC50	20 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
2-[[4-(1H-indol-3-yl)cyclohexyl]amino]-2-[1-[(E)-3-(3,4,5-trifluorophenyl)prop-2-enoyl]piperidin-4-yl]acetic acid	IC50	20 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
N-[5-chloro-2-(thiophen-2-ylsulfonylamino)phenyl]-1-benzofuran-2-sulfonamide	IC50	20 nM	US-9603834: 1,2- bis-sulfonamide derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]-methylamino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-chloro-3-(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	21 nM	US-8906911: Chemokine receptor antagonists
CHEMBL1922822	IC50	21 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
N-{5-chloro-2-[(pyridin-3-ylmethyl)thio]phenyl}-1-benzofuran-2-sulfonamide	IC50	22 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
N-{2-[(3-aminobenzyl)sulfonyl]-5-fluorophenyl}-1-benzofuran-2-sulfonamide	IC50	22 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
N-{2-[(3-aminobenzyl)sulfonyl]-5-chlorophenyl}-1-benzofuran-2-sulfonamide	IC50	23 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
CHEMBL1922814	IC50	23 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
[5-[(3-methoxyoxan-4-yl)amino]-2-methyl-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-3a-yl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	IC50	24 nM	US-8822460: Fused cyclopentyl antagonists of CCR2
2-[[4-(1H-pyrrolo[3,2-b]pyridin-3-yl)cyclohexyl]amino]-2-[1-[(E)-3-(3,4,5-trifluorophenyl)prop-2-enoyl]piperidin-4-yl]acetamide	IC50	25 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
4-chloro-N-[5-chloro-2-(methylthio)phenyl]-2-fluorobenzenesulfonamide	IC50	25 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
N-(2-{[(5-amino-1H-pyrazol-3-yl)methyl]thio}-5-chlorophenyl)-1-benzofuran-2-sulfonamide	IC50	25 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
CHEMBL1922789	IC50	25 nM	US-8921559: 4-substituted-cyclohexylamino-4-piperidinyl-acetamide antagonists of CCR2
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[2,5-bis(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	IC50	25.9 nM	US-8906911: Chemokine receptor antagonists
N-[5-chloro-2-(methylthio)phenyl]-1-benzofuran-2-sulfonamide	IC50	26 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
N-[2-(benzylsulfinyl)-5-chlorophenyl]-1-benzofuran-2-sulfonamide	IC50	27 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-[[(3S,4R)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[5-(trifluoromethyl)pyridazin-3-yl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	28 nM	US-8906911: Chemokine receptor antagonists
N-(2-{[(6-aminopyridin-2-yl)methyl]sulfinyl}-5-chlorophenyl)-1-benzofuran-2-sulfonamide	IC50	28 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-fluoro-3-(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	29 nM	US-8906911: Chemokine receptor antagonists
N-{5-chloro-2-[(pyridin-2-ylmethyl)sulfinyl]-phenyl}-1-benzofuran-2-sulfonamide	IC50	29 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
N-{5-chloro-2-[(pyridin-2-ylmethyl)sulfonyl]-phenyl}-1-benzofuran-2-sulfonamide	IC50	29 nM	US-9663460: Sulfur derivatives as chemokine receptor modulators
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]-methylamino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	30 nM	US-8906911: Chemokine receptor antagonists
[(2R,3aR,6aR)-2-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[2-fluoro-5-(trifluoromethyl)phenyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	31 nM	US-8906911: Chemokine receptor antagonists
[(2R,3aR,6aR)-2-[[(3S,4R)-3-methoxyoxan-4-yl]amino]-2,3,4,5,6,6a-hexahydro-1H-pentalen-3a-yl]-[(1S,4S)-5-[4-(trifluoromethyl)-2-pyridinyl]-2,5-diazabicyclo[2.2.1]heptan-2-yl]methanone	KI	32 nM	US-8906911: Chemokine receptor antagonists

ChEMBL bioactivities

3174 potent at pChembl≥5 of 3267 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.52	IC50	0.03	nM	CHEMBL41275
10.40	IC50	0.04	nM	PLERIXAFOR
10.40	ED50	0.04	nM	CHEMBL512607
10.15	ED50	0.07	nM	CHEMBL467070
10.10	IC50	0.08	nM	CHEMBL41275
10.10	ED50	0.08	nM	CHEMBL512615
10.05	IC50	0.09	nM	PLERIXAFOR
10.05	ED50	0.09	nM	CHEMBL513863
10.05	ED50	0.09	nM	CHEMBL468733
10.05	ED50	0.09	nM	CHEMBL453720
10.00	IC50	0.1	nM	CHEMBL494191
10.00	Kd	0.1	nM	VERCIRNON
9.89	IC50	0.13	nM	CHEMBL3770912
9.82	IC50	0.15	nM	CHEMBL230933
9.70	IC50	0.2	nM	CHEMBL3233186
9.70	IC50	0.2	nM	CHEMBL3233188
9.70	IC50	0.2	nM	CHEMBL258205
9.70	IC50	0.2	nM	CHEMBL494191
9.70	ED50	0.2	nM	CHEMBL506023
9.70	IC50	0.2	nM	CHEMBL502247
9.64	Kd	0.23	nM	CHEMBL2426341
9.64	IC50	0.23	nM	CHEMBL437359
9.62	IC50	0.24	nM	CHEMBL3577945
9.60	IC50	0.25	nM	CHEMBL3263286
9.60	IC50	0.25	nM	CHEMBL41275
9.52	IC50	0.3	nM	CHEMBL522688
9.52	IC50	0.3	nM	CHEMBL4764460
9.52	IC50	0.3	nM	CHEMBL497202
9.52	IC50	0.3	nM	CHEMBL1090893
9.49	IC50	0.32	nM	CHEMBL231039
9.47	IC50	0.34	nM	CHEMBL3233186
9.43	IC50	0.37	nM	CHEMBL497202
9.42	Ki	0.3802	nM	CHEMBL4544504
9.40	IC50	0.4	nM	CHEMBL3577948
9.40	Ki	0.4	nM	CHEMBL4483373
9.40	Ki	0.4	nM	CHEMBL4544504
9.40	IC50	0.4	nM	BMS-741672
9.40	IC50	0.4	nM	CHEMBL1092678
9.37	IC50	0.43	nM	CHEMBL230281
9.37	IC50	0.4266	nM	CHEMBL230281
9.36	ED50	0.44	nM	CHEMBL512094
9.35	Ki	0.4467	nM	CHEMBL4483373
9.32	Kd	0.48	nM	MK-0812
9.30	IC50	0.5	nM	PF-4136309
9.30	IC50	0.5	nM	CHEMBL3233187
9.30	IC50	0.5	nM	CHEMBL1091605
9.30	IC50	0.5	nM	CHEMBL3577946
9.30	IC50	0.5	nM	CHEMBL271828
9.30	ED50	0.5	nM	CHEMBL444736
9.30	ED50	0.5	nM	CHEMBL526704

PubChem BioAssay actives

2679 with measured affinity, of 3705 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
dimethyl-[[4-[[3-(4-methylphenyl)-8,9-dihydro-7H-benzo[7]annulene-6-carbonyl]amino]phenyl]methyl]-(oxan-4-yl)azanium chloride	381444: Displacement of [125I]MCP1 from CCR2/CXCR4 expressed in CHOK1 cells	ic50	<0.0001	uM
Plerixafor	381445: Displacement of [125I]SDF1alpha from CCR2/CXCR4 expressed in CHOK1 cells	ic50	<0.0001	uM
4-tert-butyl-N-[4-chloro-2-(1-oxidopyridin-1-ium-4-carbonyl)phenyl]benzenesulfonamide	1957043: Binding affinity to CCR2 (unknown origin) assessed as dissociation constant	kd	0.0001	uM
trans-(1S,3R)-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-[(1S,3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]-1-propan-2-ylcyclopentane-1-carboxamide	290742: Inhibition of chemotaxis in human MCP1 monocytes	ic50	0.0001	uM
trans-(1S,3R)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-[(3-methyloxan-4-yl)amino]-1-propan-2-ylcyclopentane-1-carboxamide	418627: Antagonist activity at human CCR2 receptor expressed in CHO cells by chemotaxis assay	ic50	0.0001	uM
N-[2-[[(3S,4S)-1-[4-(1,3-benzodioxol-5-yl)-4-hydroxycyclohexyl]-4-ethoxypyrrolidin-3-yl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	771594: Displacement of [3H]INCB3344 from human CCR2 receptor expressed in human U2OS cell membranes assessed as association and dissociation of radioligand	kd	0.0002	uM
N-[2-[[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-[(4-methylsulfanylphenyl)sulfonylmethyl]cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	375876: Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced chemotaxis	ic50	0.0002	uM
(E)-3-(3,4-dichlorophenyl)-1-[4-[2-hydroxy-1-[4-(1H-indol-3-yl)piperidin-1-yl]ethyl]piperidin-1-yl]prop-2-en-1-one	331219: Binding affinity at human CCR2 receptor	ic50	0.0002	uM
trans-(1S,3R)-1-cyclopropyl-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-3-[(1S,3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]cyclopentane-1-carboxamide	290742: Inhibition of chemotaxis in human MCP1 monocytes	ic50	0.0002	uM
(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-propylcyclohexyl]-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-2-one	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0002	uM
N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(propan-2-ylsulfonylmethyl)cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0002	uM
N-[(3S)-1-[(1S,2R,4R)-2-(tert-butylsulfonylmethyl)-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0002	uM
N-[2-[[(1S,2R,4R)-4-(dimethylamino)-2-[(4-methylsulfanylphenyl)sulfonylmethyl]cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	375875: Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced calcium flux by fluorescence-imaging plate reader assay	ic50	0.0003	uM
trans-(1R,3R)-N-[[3-fluoro-5-(trifluoromethyl)phenyl]methyl]-1-(2-methylpropyl)-3-[(1S,3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]cyclopentane-1-carboxamide	290742: Inhibition of chemotaxis in human MCP1 monocytes	ic50	0.0003	uM
trans-(1S,3R)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-[(3-ethyloxan-4-yl)amino]-1-propan-2-ylcyclopentane-1-carboxamide	418627: Antagonist activity at human CCR2 receptor expressed in CHO cells by chemotaxis assay	ic50	0.0003	uM
N-[(3S)-1-[(1S,2R,4R)-2-(benzenesulfonylmethyl)-4-[ethyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	474888: Displacement of [125I]-MCP1 from CCR2 in human THP1 cells after 30 mins	ic50	0.0003	uM
3-[1-[(3aS,5S,6aR)-3a-[6-(trifluoromethyl)-2,4-dihydro-1,3-benzoxazine-3-carbonyl]-2,3,4,5,6,6a-hexahydrocyclopenta[b]furan-5-yl]piperidin-4-yl]-N-methylbenzamide	1138982: Displacement of labeled MCP-1 from human CCR2 expressed in THP1 cells	ic50	0.0003	uM
N-[(3S)-1-[(1S,2R,4R)-2-acetamido-4-(tert-butylamino)cyclohexyl]-2-oxopyrrolidin-3-yl]-6-tert-butylpyridine-2-carboxamide	1710272: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay	ic50	0.0003	uM
N-[(1R,2S,5R)-5-[methyl(propan-2-yl)amino]-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]methanesulfonamide	1542565: Displacement of [125I]MCP1 from CCR2 in human PBMC measured after 30 mins	ic50	0.0004	uM
2-amino-6-[(3-bromo-4-chlorophenyl)methyl]-5-propan-2-yl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0004	uM
(3S)-1-[(1S,2S,4R)-4-[methyl(propan-2-yl)amino]-2-propan-2-ylcyclohexyl]-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-2-one	1226281: Inhibition of [125I]hMCP1 binding to CCR2 in human PBMC incubated for 30 mins at room temperature	ic50	0.0004	uM
(2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(methylcarbamoylamino)-1,3-thiazol-4-yl]-4-(4-phenylpiperidin-1-yl)butanamide	289625: Displacement of [125I]MCP1 from human CCR2 expressed in monocytes	ic50	0.0004	uM
N-[(3S)-1-[(1S,2R,4R)-2-[(4-methylphenyl)sulfonylmethyl]-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	474888: Displacement of [125I]-MCP1 from CCR2 in human THP1 cells after 30 mins	ic50	0.0004	uM
2-amino-5-cyclopropyl-6-[(3,4-dichlorophenyl)methyl]-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0004	uM
N-[2-[[(2S,3S)-1-(2,2-dimethylpropylamino)-3-hydroxyhexan-2-yl]amino]-2-oxoethyl]-2-(propan-2-ylcarbamoylamino)-5-(trifluoromethyl)benzamide	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0004	uM
N-[2-[[(2S,3S)-3-hydroxy-1-(2-methylpropylamino)hexan-2-yl]amino]-2-oxoethyl]-2-(propan-2-ylcarbamoylamino)-5-(trifluoromethyl)benzamide	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0004	uM
[(1S,3R)-3-[[(3S,4S)-3-methoxyoxan-4-yl]amino]-1-propan-2-ylcyclopentyl]-[3-(trifluoromethyl)-7,8-dihydro-5H-1,6-naphthyridin-6-yl]methanone	1200137: Displacement of 0.1 nM [125I]CCL2 from human CCR2 expressing human U2OS cell membrane by scintillation spectrometry	kd	0.0005	uM
N-[2-[(3S)-3-[[4-hydroxy-4-(5-pyrimidin-2-yl-2-pyridinyl)cyclohexyl]amino]pyrrolidin-1-yl]-2-oxoethyl]-3-(trifluoromethyl)benzamide	662875: Inhibition of CCR2-mediated Erk phosphorylation	ic50	0.0005	uM
2-(cyclohexanecarbonylamino)-N-[2-oxo-2-[[(1S,2R)-2-[(4-sulfamoylbenzoyl)amino]cyclohexyl]amino]ethyl]-5-(trifluoromethyl)benzamide	315320: Antagonist activity at human CCR2 in PBMCs assessed as inhibition of chemotaxis	ic50	0.0005	uM
N-[(3S)-1-[(1S,2R,4R)-2-(benzenesulfonylmethyl)-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0005	uM
(3S)-1-[(1S,2R,4R)-2-ethyl-4-[methyl(propan-2-yl)amino]cyclohexyl]-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-2-one	1226281: Inhibition of [125I]hMCP1 binding to CCR2 in human PBMC incubated for 30 mins at room temperature	ic50	0.0005	uM
3-tert-butyl-N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(propan-2-ylsulfonylmethyl)cyclohexyl]-2-oxopyrrolidin-3-yl]benzamide	1129742: Displacement of [125I]-labeled human MCP1 from CCR2 in human PBMC	ic50	0.0005	uM
(E)-3-(3,5-difluorophenyl)-1-[4-[2-hydroxy-1-[4-(1H-indol-3-yl)piperidin-1-yl]ethyl]piperidin-1-yl]prop-2-en-1-one	331219: Binding affinity at human CCR2 receptor	ic50	0.0006	uM
N-[3-[1-[1-[1-[(E)-3-(3,4-dichlorophenyl)prop-2-enoyl]piperidin-4-yl]-2-hydroxyethyl]piperidin-4-yl]-1H-indol-5-yl]methanesulfonamide	331219: Binding affinity at human CCR2 receptor	ic50	0.0006	uM
2-amino-6-[(3,4-dichlorophenyl)methyl]-5-propan-2-yl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0006	uM
2-[[4-[4-chloro-2-[[4-chloro-3-(trifluoromethyl)phenyl]sulfonylamino]phenoxy]benzoyl]amino]ethyl thiocyanate	1732352: Displacement of [3H]-CCR2-RA-(R) from human CCR2b expressed in human U2OS cell membranes pre-incubated for 4 hrs before radio ligand addition and measured after 20 mins by scintillation counting method	ki	0.0006	uM
N-[(1R,2S,5R)-5-(tert-butylamino)-2-[(3S)-3-[(6-tert-butylpyrido[3,2-d]pyrimidin-4-yl)amino]-2-oxopyrrolidin-1-yl]cyclohexyl]acetamide	1710272: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay	ic50	0.0006	uM
2-(2-acetamido-1,3-thiazol-4-yl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-[(3’R)-3’-methylspiro[indene-1,4’-piperidine]-1’-yl]butanamide	289650: Inhibition of MCP1-stimulated chemotaxis in monocytes transfected with human CCR2	ic50	0.0006	uM
2-(ethylcarbamoylamino)-N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-propylcyclohexyl]-2-oxopyrrolidin-3-yl]-5-(trifluoromethyl)benzamide	1226282: Antagonist activity against CCR2 in human PBMC assessed as inhibition of MCP1-induced chemotaxis at 37 degC	ic50	0.0006	uM
N-[(3S)-1-[(1S,2R,4R)-2-(ethylsulfonylmethyl)-4-[methyl(propan-2-yl)amino]cyclohexyl]-2-oxopyrrolidin-3-yl]-3-(trifluoromethyl)benzamide	1129745: Antagonist activity at CCR2 in human monocytes assessed as reduction of chemotaxis in presence of 0.1 M BSA	ic50	0.0006	uM
[6-(3,4-dichloroanilino)-2-(fluoromethyl)-5-methylpyrimidin-4-yl]-[4-[[(3S,4S)-3-methoxyoxan-4-yl]amino]piperidin-1-yl]methanone	734806: Displacement of [125I]MCP1 from CCR2 in human THP1 cell membranes after 8 hrs by scintillation counting analysis	ki	0.0006	uM
N-[2-[[(1S,2R,4R)-4-(diethylamino)-2-[(4-methylsulfanylphenyl)sulfonylmethyl]cyclohexyl]amino]-2-oxoethyl]-3-(trifluoromethyl)benzamide	375875: Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced calcium flux by fluorescence-imaging plate reader assay	ic50	0.0007	uM
(2S)-2-(2-acetamido-1,3-thiazol-4-yl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-(4-phenylpiperidin-1-yl)butanamide	289650: Inhibition of MCP1-stimulated chemotaxis in monocytes transfected with human CCR2	ic50	0.0007	uM
N-[(1R,2S,5R)-5-[methyl(propan-2-yl)amino]-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide	1542579: Inhibition of CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 10 mins by calcein-AM dye based fluorescence assay	ic50	0.0007	uM
2-(2-acetamido-1,3-thiazol-4-yl)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-4-spiro[indene-1,4’-piperidine]-1’-ylbutanamide	289650: Inhibition of MCP1-stimulated chemotaxis in monocytes transfected with human CCR2	ic50	0.0007	uM
6-tert-butyl-N-[(3S)-1-[(1S,2R,4R)-4-[methyl(propan-2-yl)amino]-2-(methylsulfonylmethyl)cyclohexyl]-2-oxopyrrolidin-3-yl]pyridine-2-carboxamide	1129742: Displacement of [125I]-labeled human MCP1 from CCR2 in human PBMC	ic50	0.0007	uM
2-amino-6-[(3-bromophenyl)methyl]-5-cyclopropyl-1H-[1,2,4]triazolo[1,5-a]pyrimidin-7-one	1528114: Displacement of [3H]-CCR2-RA-[R] from human CCR2 expressed in human U2OS cells incubated for 2 hrs by scintillation spectrometric method	ki	0.0008	uM
N-[(1R,2S,5R)-5-(tert-butylamino)-2-[(3S)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide	1710272: Antagonist activity at CCR2 in human THP1 cells assessed as reduction in MCP1-induced chemotaxis measured after 30 mins by calcein-AM dye based fluorescence assay	ic50	0.0008	uM
2-amino-N-[2-[[(3R)-1-[(2,4-dimethylphenyl)methyl]pyrrolidin-3-yl]amino]-2-oxoethyl]-5-(trifluoromethyl)benzamide	325951: Antagonist activity at human CCR2 in THP1 cells assessed as inhibition of MCP1-induced chemotaxis	ic50	0.0008	uM
(2S)-N-[[3,5-bis(trifluoromethyl)phenyl]methyl]-2-[2-(methylcarbamoylamino)-1,3-thiazol-4-yl]-4-spiro[indene-1,4’-piperidine]-1’-ylbutanamide	289625: Displacement of [125I]MCP1 from human CCR2 expressed in monocytes	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Nickel	affects expression, decreases expression, increases expression, decreases reaction	4
Arsenic	affects expression, affects methylation, affects cotreatment, decreases expression	3
Dinitrochlorobenzene	decreases expression, increases expression	3
Simvastatin	affects binding, decreases activity, decreases expression, decreases reaction, increases expression	3
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression, increases expression	2
Lipopolysaccharides	decreases expression, increases expression, affects response to substance, affects cotreatment, decreases reaction	2
Piperidines	affects binding, decreases activity, decreases reaction	2
Cyclosporine	affects cotreatment, increases expression	2
Antirheumatic Agents	decreases expression	2
Zinc Sulfate	increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
captax	increases expression	1
trichostatin A	affects expression, decreases reaction	1
proanthocyanidin	decreases expression	1
sulforaphane	decreases expression	1
sodium arsenite	increases expression	1
ammonium hexachloroplatinate	decreases expression	1
4-phenylenediamine	decreases expression	1
aflatoxin B2	increases methylation	1
2,2’,3’,4,4’,5-hexachlorobiphenyl	affects expression	1
nickel sulfate	decreases expression	1
3-chlorophenol	increases expression	1
sodium chlorate	decreases sulfation, decreases reaction, increases activity	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment, decreases expression	1
nefazodone	affects cotreatment, increases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	decreases reaction, increases expression	1
4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole	decreases expression, decreases reaction	1
SB 203580	decreases reaction, increases expression	1
U 0126	decreases reaction, increases expression	1
1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphorylcholine	increases expression	1

ChEMBL screening assays

426 unique, capped per target: 277 binding, 149 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1001496	Binding	Displacement of [125I]MCP1 from CCR2 in human PBMC by millipore filter plate assay	Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. — Bioorg Med Chem Lett
CHEMBL1001497	Functional	Antagonist activity at CCR2 in human PBMC assessed as MCP1-induced calcium flux by fluorescence-imaging plate reader assay	Novel sulfone-containing di- and trisubstituted cyclohexanes as potent CC chemokine receptor 2 (CCR2) antagonists. — Bioorg Med Chem Lett

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 2 transformed cell line, 2 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D95	HOS-CD4-CCR2b	Cancer cell line	Female
CVCL_1E07	GHOST(3).CCR2b	Cancer cell line	Female
CVCL_B9WZ	Abcam THP-1 CCR2 KO	Cancer cell line	Male
CVCL_E4JY	HEK293 CCR2 isoform B	Transformed cell line	Female
CVCL_KW56	PathHunter CHO-K1 CCR2 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ38	PathHunter HEK 293 CCR2 beta-arrestin	Transformed cell line	Female
CVCL_KZ94	PathHunter U2OS CCR2 Total GPCR Internalization	Cancer cell line	Female
CVCL_RQ09	ValiScreen human CCR2b	Spontaneously immortalized cell line	Female
CVCL_X628	U87.CD4.CCR2	Cancer cell line	Male
CVCL_ZJ99	Tango CCR2-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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