CCR1

Summary

CCR1 (C-C motif chemokine receptor 1, HGNC:1602) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor type 1 (P32246). Chemokine receptor that plays a crucial role in regulating immune cell migration, inflammation, and immune responses.

This gene encodes a member of the beta chemokine receptor family, which is predicted to be a seven transmembrane protein similar to G protein-coupled receptors. The ligands of this receptor include macrophage inflammatory protein 1 alpha (MIP-1 alpha), regulated on activation normal T expressed and secreted protein (RANTES), monocyte chemoattractant protein 3 (MCP-3), and myeloid progenitor inhibitory factor-1 (MPIF-1). Chemokines and their receptors mediated signal transduction are critical for the recruitment of effector immune cells to the site of inflammation. Knockout studies of the mouse homolog suggested the roles of this gene in host protection from inflammatory response, and susceptibility to virus and parasite. This gene and other chemokine receptor genes, including CCR2, CCRL2, CCR3, CCR5 and CCXCR1, are found to form a gene cluster on chromosome 3p.

Source: NCBI Gene 1230 — RefSeq curated summary.

At a glance

• GWAS associations: 16
• Clinical variants (ClinVar): 55 total
• Phenotypes (HPO): 85
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001295

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1602
Approved symbol	CCR1
Name	C-C motif chemokine receptor 1
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CKR-1, MIP1aR, CD191
Ensembl gene	ENSG00000163823
Ensembl biotype	protein_coding
OMIM	601159
Entrez	1230

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000296140, ENST00000903399, ENST00000903400, ENST00000944216, ENST00000944217

RefSeq mRNA: 1 — MANE Select: NM_001295 NM_001295

CCDS: CCDS2737

Canonical transcript exons

ENST00000296140 — 2 exons

Exon	Start	End
ENSE00001078624	46208282	46208313
ENSE00001209137	46201711	46204324

Expression profiles

Bgee: expression breadth ubiquitous, 244 present calls, max score 96.71.

FANTOM5 (CAGE): breadth broad, TPM avg 12.4690 / max 758.7338, expressed in 472 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
41951	8.9377	422
41954	1.4345	283
41955	1.2673	232
41953	0.5145	186
41956	0.1996	111
41952	0.1154	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.71	gold quality
mononuclear cell	CL:0000842	96.62	gold quality
leukocyte	CL:0000738	96.51	gold quality
blood	UBERON:0000178	94.37	gold quality
granulocyte	CL:0000094	91.04	gold quality
periodontal ligament	UBERON:0008266	90.22	gold quality
buccal mucosa cell	CL:0002336	87.10	gold quality
vermiform appendix	UBERON:0001154	86.94	gold quality
spleen	UBERON:0002106	86.74	gold quality
decidua	UBERON:0002450	86.08	gold quality
bone marrow	UBERON:0002371	85.00	gold quality
placenta	UBERON:0001987	84.70	gold quality
trabecular bone tissue	UBERON:0002483	84.51	gold quality
layer of synovial tissue	UBERON:0007616	83.52	gold quality
heart right ventricle	UBERON:0002080	83.45	gold quality
bone marrow cell	CL:0002092	82.73	gold quality
lower lobe of lung	UBERON:0008949	82.21	gold quality
caecum	UBERON:0001153	81.98	gold quality
gall bladder	UBERON:0002110	81.62	gold quality
tibia	UBERON:0000979	80.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.45	silver quality
superficial temporal artery	UBERON:0001614	79.98	gold quality
amniotic fluid	UBERON:0000173	79.87	gold quality
pericardium	UBERON:0002407	79.49	gold quality
germinal epithelium of ovary	UBERON:0001304	78.94	gold quality
lung	UBERON:0002048	78.94	gold quality
pleura	UBERON:0000977	78.91	gold quality
parietal pleura	UBERON:0002400	78.74	gold quality
lymph node	UBERON:0000029	78.47	gold quality
upper lobe of lung	UBERON:0008948	78.23	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	19.40
E-MTAB-8498	yes	10.13

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BGLAP	Repression
SP7	Repression

Upstream regulators (CollecTRI, top): CREB3, MAF, NFKB, STAT1

miRNA regulators (miRDB)

56 targeting CCR1, 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-4795-3P	100.00	74.62	4024
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-9718	99.94	68.91	918
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-3681-5P	99.82	66.88	387
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6892-3P	99.68	66.40	1178
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-6849-5P	99.64	66.00	352
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-5584-5P	99.49	68.22	2814
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378

Literature-anchored findings (GeneRIF, showing 40)

• agonistic effect of truncated leukotactin-1 on receptor activity (PMID:11832479)
• We determined that human serum contains a molecule that suppresses RANTES (CCL5) binding to endothelial cells, PBMC and CHO cells. (PMID:11920567)
• CCR1, CCR6, and CXCR6 are preferentially expressed by the low cytokine-producing CD8 and CD4(-)CD8(-) subsets of natural killer T-cells. (PMID:12070001)
• chronic hepatitis C, but not hepatitis B, infection alters surface expression of CCR1 and CCR5 in T cells, resulting in lower CC chemokine responsiveness. (PMID:12085329)
• Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors (PMID:12270118)
• Potential interaction between this protein and it ligand, CCL3 is induced by endogenously produced interleukin-1 in human hepatomas. (PMID:12651617)
• Efficient leukocyte arrest in flow but not transmigration may thus require the presentation of RANTES oligomers to bridge surface-bound RANTES and CCR1. (PMID:12763925)
• Eosinophil CCR1 expression is non-normally distributed in atopics, although higher CCR1 expression levels are not predictive of a diagnosis of atopy or atopic disease. (PMID:12794150)
• Trophoblasts acquire CCR1 as they differentiate to an invasive phenotype at the villus-anchoring sites. (PMID:14530297)
• neuronal CCR1 is not a generalized marker of neurodegeneration. Rather, it appears to be part of the neuroimmune response to Abeta42-positive neuritic plaques (PMID:14595653)
• LZIP binds to CCR1 and the interaction between CCR1 and LZIP participates in regulation of Lkn-1-dependent cell migration without affecting the chemotactic activities of other CC chemokines that bind to CCR1. (PMID:15001559)
• Leishmania infantum infection causes a down-regulation of the CCR1 gene and protein expression (PMID:15103513)
• CCR1 signalling induced by RANTES or Met-RANTES has no effect on proliferation and apoptosis of mesangial cells. (PMID:15265234)
• Data show that cross-talk between CC chemokine receptor R1-mediated signaling pathways and FcepsilonRI-mediated signaling pathways affects degranulation positively but affects chemotaxis of mast cells adversely. (PMID:15337751)
• PLP2/A4 has a role in the chemotactic processes via CCR1 (PMID:15474493)
• analysis of binding of mutant CCR1 to UCB 35625 (PMID:15548526)
• chemokine (C-C motif) ligand 23-induced endothelial cell migration, indicating that endothelial cell migration was mediated through CCR1 (PMID:15927850)
• Increased constitutive expression of CCR1 in peritoneal macrophages of women with endometriosis may play a contributory role in the pathogenesis of endometriosis. (PMID:15950672)
• CC chemokine-4 (HCC-4)/CCL16 transduces signals differently from other CCR1-dependent chemokines and may play different roles in the immune response. (PMID:16226254)
• analysis of CCR1 chemokine receptor structure and BX 471 antagonist binding followed by experimental validation (PMID:16837468)
• expression of AR down-regulates the migratory responses of human prostate cancer cells via CXCR4 and CCR1 (PMID:16969502)
• regulatory role of LZIP in the NF-kappaB pathway that is induced by CCR1-dependent chemokines (PMID:17192849)
• CCR1 protein expression is associated with renal function in allografts and is restricted to monocytes, CD20-positive B cells and DC-specific ICAM-3 grabbing nonintegrin (DC-SIGN)-positive dendritic cells. (PMID:17298994)
• CCR1 has an important role in hepatocellular carcinoma (HCC) cells, HCCLM3 invasion and that CCR1 might be a new target of HCC treatment (PMID:17336272)
• RSV-CM causes a biphasic up-regulation of surface CCR1 on monocytes, which is dependent on an intact cytoskeleton, requires new gene transcription and protein synthesis, and is mediated in part by the proinflammatory cytokines TNF-alpha and IL-1. (PMID:17389578)
• These results demonstrate that 9-cis-Retinoic acid transduces the signal through p38 MAPK and ERK1/2 for CCR1 and CCR2 up-regulation. (PMID:17464174)
• Significantly higher expression of CCR1 is associated with tumor metastasis and local host defense in oral squamous cell carcinoma (PMID:17914560)
• CCR1 might be involved in the pathogenesis of asthma, through the activation of airway smooth muscle cells by its ligands. (PMID:18178867)
• analysis of binding of CC-chemokine receptor 1 (CCR1) to CC-chemokine 3 and 5 (CCL3 and CCL5) (PMID:18559339)
• CCR1 contributes to human non-small cell lung cancer cell migration by stimulating cell invasion, independent of cell proliferation. (PMID:18972130)
• infiltrated neutrophils from patients with chronic inflammatory lung diseases and rheumatoid arthritis highly express CCR1, CCR2, CCR3, CCR5, CXCR3, and CXCR4 (PMID:19017998)
• CCL14a analog CCL14a(12-74) was isolated from blood filtrate and found to bind to receptors CCR1 to CCR5, activating intracellular calcium mobizilation, and to bind the human HCMV-encoded chemokine receptor US28, inhibiting HIV infection (PMID:19553544)
• marked upregulation of RANTES, CCR1, and CCR5 in patients with hepatic cirrhosis, confirming activation of the CC chemokine system in human fibrogenesis. (PMID:19603542)
• The expression CCR1 in colorectal carcinoma is correlated with lymph node metastasis. (PMID:19664396)
• The ability of CCR1 to signal through Galpha(14/16) thus provides a linkage for chemokines to regulate NF-kappaB-dependent responses. (PMID:19687291)
• CCR1 were genes activated in late endometrial endometrioid carcinoma (stages III-IV). (PMID:20015385)
• CCR1 antagonist, BX471, did not significantly alter ICAM-3 expression in relapsing-remitting multiple sclerosis patients. (PMID:20086017)
• These data suggest that CCR1 may be useful for lymphoma classification and support a role for chemokine signaling in the pathogenesis of hematolymphoid neoplasia. (PMID:20154287)
• Above median expression of CXCR2, CXCR3 and CCR1 in the tumour islets is associated with increased survival in non-small cell carcinoma, and expression of CXCR3 correlates with increased macrophage and mast cell infiltration in the tumour islets. (PMID:20429924)
• TLR2 negatively regulates CCR1, CCR2, and CCR5 on blood monocytes by activating chemokine-dependent down-modulation and providing a molecular mechanism for inhibiting monocyte migration after pathogen recognition. (PMID:21148810)

Cross-species orthologs

10 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	Ccr1	ENSMUSG00000025804
mus_musculus	Ccr1l1	ENSMUSG00000064039
rattus_norvegicus	Ccr1l1	ENSRNOG00000083822
rattus_norvegicus	Ccr1	ENSRNOG00000086224

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), 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 1 — P32246 (reviewed: P32246)

Alternative names: HM145, LD78 receptor, Macrophage inflammatory protein 1-alpha receptor, RANTES-R

All UniProt accessions (2): P32246, Q5U003

UniProt curated annotations — full annotation on UniProt →

Function. Chemokine receptor that plays a crucial role in regulating immune cell migration, inflammation, and immune responses. Contributes to the inflammatory response by recruiting immune cells, such as monocytes, macrophages, T-cells, and dendritic cells, to sites of inflammation for the clearance of pathogens and the resolution of tissue damage. When activated by its ligands including CCL3, CCL5-9, CCL13-16 and CCL23, triggers a signaling cascade within immune cells, leading to their migration towards the source of the chemokine. For example, mediates neutrophil migration after activation by CCL3 leading to the sequential release of TNF and leukotriene B4. Also mediates monocyte migration upon CXCL4 binding. Activation by CCL5 results in neuroinflammation through the ERK1/2 signaling pathway.

Subunit / interactions. Interacts with CREB3. Interacts with CCL3. Interacts with CCL15. Interacts with CCL23. Interacts with GNAI1. Interacts with PF4/CXCL4. (Microbial infection) Interacts with Kaposi virus protein vCCL2; this interaction blocks calcium mobilization induced by endogenous chemokines.

Subcellular location. Cell membrane.

Tissue specificity. Widely expressed in different hematopoietic cells.

Induction. Up-regulated by CREB3.

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

RefSeq proteins (1): NP_001286* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR002236	Chemokine_CCR1	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (42 total): helix 13, topological domain 8, transmembrane region 7, turn 5, strand 4, disulfide bond 2, chain 1, glycosylation site 1, sequence conflict 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7VL9	ELECTRON MICROSCOPY	2.6
7VLA	ELECTRON MICROSCOPY	2.7
7VL8	ELECTRON MICROSCOPY	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P32246-F1	83.49	0.55

Antibody-complex structures (SAbDab): 3 — 7VL8, 7VL9, 7VLA

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 (2): 24–273, 106–183

Glycosylation sites (1): 5

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
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-162582	Signal Transduction
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

MSigDB gene sets: 619 (showing top): GOBP_MYELOID_CELL_DIFFERENTIATION, TAKEDA_TARGETS_OF_NUP98_HOXA9_FUSION_6HR_DN, GOBP_POSITIVE_REGULATION_OF_CALCIUM_ION_TRANSPORT, MODULE_92, GOBP_REGULATION_OF_OSTEOCLAST_DIFFERENTIATION, GOBP_DENDRITIC_CELL_MIGRATION, MCLACHLAN_DENTAL_CARIES_UP, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_MYELOID_LEUKOCYTE_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, MODULE_64

GO Biological Process (33): dendritic cell chemotaxis (GO:0002407), monocyte chemotaxis (GO:0002548), calcium ion transport (GO:0006816), intracellular calcium ion homeostasis (GO:0006874), exocytosis (GO:0006887), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cell adhesion (GO:0007155), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger (GO:0007187), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), response to wounding (GO:0009611), negative regulation of gene expression (GO:0010629), cytokine-mediated signaling pathway (GO:0019221), calcium-mediated signaling (GO:0019722), positive regulation of cell migration (GO:0030335), negative regulation of bone mineralization (GO:0030502), positive regulation of osteoclast differentiation (GO:0045672), positive regulation of inflammatory response (GO:0050729), positive regulation of calcium ion transport (GO:0051928), cell chemotaxis (GO:0060326), chemokine-mediated signaling pathway (GO:0070098), positive regulation of ERK1 and ERK2 cascade (GO:0070374), positive regulation of monocyte chemotaxis (GO:0090026), positive regulation of neuroinflammatory response (GO:0150078), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186), canonical NF-kappaB signal transduction (GO:0007249), signal transduction involved in regulation of gene expression (GO:0023019), cellular response to cytokine stimulus (GO:0071345), negative regulation of cytokine production involved in inflammatory response (GO:1900016)

GO Molecular Function (8): phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), chemokine receptor activity (GO:0004950), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), chemokine (C-C motif) ligand 7 binding (GO:0035717), chemokine (C-C motif) ligand 5 binding (GO:0071791), 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-9 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
C-C chemokine binding	3
leukocyte chemotaxis	2
G protein-coupled receptor signaling pathway	2
chemokine binding	2
cellular anatomical structure	2
dendritic cell migration	1
mononuclear cell migration	1
myeloid leukocyte migration	1
metal ion transport	1
intracellular monoatomic cation homeostasis	1
calcium ion homeostasis	1
vesicle-mediated transport	1
secretion by cell	1
vesicle fusion to plasma membrane	1
response to chemical	1
taxis	1
defense response	1
immune system process	1
response to stimulus	1
cellular process	1
signal transduction	1
regulation of biological quality	1
cell communication	1
signaling	1
response to stress	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
cell surface receptor signaling pathway	1
cellular response to cytokine stimulus	1
intracellular signaling cassette	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
negative regulation of ossification	1
bone mineralization	1
regulation of bone mineralization	1
negative regulation of biomineral tissue development	1
positive regulation of myeloid leukocyte differentiation	1
osteoclast differentiation	1

Protein interactions and networks

STRING

2522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR1	CCL5	P13501	999
CCR1	CCL3	P10147	998
CCR1	CCL2	P13500	997
CCR1	CCL4	P13236	996
CCR1	CCL8	P78388	996
CCR1	CCL7	P80098	996
CCR1	CCL15	Q16663	995
CCR1	CXCL8	P10145	993
CCR1	CCL23	P55773	992
CCR1	CCL16	O15467	991
CCR1	CCL11	P50877	991
CCR1	CCL14	Q16627	991
CCR1	CCL13	Q99616	990
CCR1	CXCL10	P02778	984
CCR1	CCR5	P51681	982

IntAct

31 interactions, top by confidence:

A	B	Type	Score
CCL5	CCL5	psi-mi:“MI:0914”(association)	0.860
CCR1	PLP2	psi-mi:“MI:0915”(physical association)	0.660
PLP2	CCR1	psi-mi:“MI:0915”(physical association)	0.660
CCR1	PLP2	psi-mi:“MI:0403”(colocalization)	0.660
CCR1	TMX1	psi-mi:“MI:0915”(physical association)	0.560
CCR1	CREB3	psi-mi:“MI:0915”(physical association)	0.540
CCR1	CREB3	psi-mi:“MI:0403”(colocalization)	0.540
CCR1	CCL5	psi-mi:“MI:0915”(physical association)	0.500
CCR1	MBP	psi-mi:“MI:2364”(proximity)	0.450
PRNP	CCR1	psi-mi:“MI:2364”(proximity)	0.450
MBP	CCR1	psi-mi:“MI:0915”(physical association)	0.450
PRNP	CCR1	psi-mi:“MI:0915”(physical association)	0.450
CCR1	HNRNPU	psi-mi:“MI:0915”(physical association)	0.400
CD74	CCR1	psi-mi:“MI:0915”(physical association)	0.370
GRAMD1A	CCR1	psi-mi:“MI:0915”(physical association)	0.370
LETMD1	CCR1	psi-mi:“MI:0915”(physical association)	0.370
FAN1	CCR1	psi-mi:“MI:0915”(physical association)	0.370
QSOX1	CCR1	psi-mi:“MI:0915”(physical association)	0.370
TMEFF1	CCR1	psi-mi:“MI:0915”(physical association)	0.370
CCR1	ATP5F1B	psi-mi:“MI:0914”(association)	0.350
CCR1	VPS37C	psi-mi:“MI:0914”(association)	0.350
CCR1	UBA6	psi-mi:“MI:0914”(association)	0.350
CCR1	TMX1	psi-mi:“MI:0915”(physical association)	0.000
rpoB	CCR1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (359): PAG1 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), GNG10 (Affinity Capture-MS), YES1 (Affinity Capture-MS), EPHA2 (Affinity Capture-MS), SETD7 (Affinity Capture-MS), GNA13 (Affinity Capture-MS), GNAQ (Affinity Capture-MS), LENG1 (Affinity Capture-MS), LAMTOR4 (Affinity Capture-MS), C12orf75 (Affinity Capture-MS), GNG10 (Affinity Capture-MS), PAG1 (Affinity Capture-MS), GAP43 (Affinity Capture-MS), EPHA2 (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: A0A4W3GG95, A0A6I8PUB9, A6QLE7, D4A7K7, E7FEL0, E9QJ73, O00254, O08675, O46685, P0C0W8, P0C5J4, P32246, P32249, P32250, P34996, P35366, P35383, P41231, P41232, P46093, P47900, P48042, P49650, P49651, P49652, P50132, P56482, P58826, P59902, P79928, P97266, Q149R9, Q15743, Q1JQB3, Q2Y2P0, Q3U6B2, Q3ZC80, Q4G072, Q4KLH9, Q5E9H8

SIGNOR signaling

6 interactions.

A	Effect	B	Mechanism
CCL3	up-regulates	CCR1	binding
CCL5	up-regulates	CCR1	binding
CCL7	up-regulates	CCR1	binding
CCR1	up-regulates	Differentiation
CCL3	“up-regulates activity”	CCR1	binding
CCR1	“up-regulates activity”	ERK1/2	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	35
Likely benign	12
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

221 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
3:46204320: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
3:46204323:TC:T	acceptor_gain	0.9800
3:46204324:CC:C	acceptor_gain	0.9800
3:46204328:C:CT	acceptor_gain	0.9800
3:46204329:A:T	acceptor_gain	0.9800
3:46204331:G:C	acceptor_gain	0.9800
3:46204332:T:TC	acceptor_gain	0.9800
3:46204331:G:GC	acceptor_gain	0.9700
3:46204332:T:C	acceptor_gain	0.9700
3:46204321:TCTC:T	acceptor_gain	0.9200
3:46204322:CTCC:C	acceptor_gain	0.9200
3:46204323:TCCT:T	acceptor_gain	0.9200
3:46208273:GACAC:G	donor_loss	0.8400
3:46208274:ACACT:A	donor_loss	0.8200

AlphaMissense

2330 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:46203852:G:C	S154R	0.997
3:46203852:G:T	S154R	0.997
3:46203854:T:G	S154R	0.997
3:46204017:C:A	W99C	0.994
3:46204017:C:G	W99C	0.994
3:46203842:A:G	W158R	0.992
3:46203842:A:T	W158R	0.992
3:46203957:G:C	S119R	0.990
3:46203957:G:T	S119R	0.990
3:46203959:T:G	S119R	0.990
3:46203390:G:C	F308L	0.989
3:46203390:G:T	F308L	0.989
3:46203392:A:G	F308L	0.989
3:46203997:C:G	C106S	0.989
3:46203998:A:T	C106S	0.989
3:46204089:G:C	N75K	0.987
3:46204089:G:T	N75K	0.987
3:46203421:G:T	P298Q	0.986
3:46203553:G:T	P254H	0.986
3:46204019:A:G	W99R	0.986
3:46204019:A:T	W99R	0.986
3:46204158:G:C	N52K	0.986
3:46204158:G:T	N52K	0.986
3:46203682:G:C	P211R	0.985
3:46203766:C:G	C183S	0.985
3:46203767:A:T	C183S	0.985
3:46203553:G:C	P254R	0.984
3:46203662:A:G	C218R	0.984
3:46204172:C:G	G48R	0.984
3:46203431:A:G	C295R	0.982

dbSNP variants (sampled 300 via entrez): RS1000013210 (3:46205541 C>G), RS1000045885 (3:46205251 A>G), RS1001099189 (3:46206211 T>G), RS1002052659 (3:46208187 C>T), RS1002104797 (3:46207748 G>A,T), RS1002612527 (3:46202875 C>T), RS1003045859 (3:46209765 G>A,C), RS1003099871 (3:46209555 C>T), RS1003878963 (3:46205964 A>C), RS1003910180 (3:46205644 T>C), RS1004024121 (3:46204463 G>A), RS1004616030 (3:46205876 T>C), RS1005665901 (3:46209767 G>A,T), RS1005668593 (3:46206948 T>C), RS1005718339 (3:46210100 T>A,C)

Disease associations

OMIM: gene MIM:601159 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

85 total (30 of 85 shown, HPO-id order):

HPO	Term
HP:0000031	Epididymitis
HP:0000083	Renal insufficiency
HP:0000099	Glomerulonephritis
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000518	Cataract
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000708	Atypical behavior
HP:0000737	Irritability
HP:0001061	Acne
HP:0001097	Keratoconjunctivitis sicca
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001269	Hemiparesis
HP:0001287	Meningitis
HP:0001288	Gait disturbance
HP:0001289	Confusion
HP:0001347	Hyperreflexia
HP:0001369	Arthritis
HP:0001482	Subcutaneous nodule
HP:0001637	Abnormal myocardium morphology
HP:0001653	Mitral regurgitation
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001701	Pericarditis
HP:0001733	Pancreatitis
HP:0001744	Splenomegaly
HP:0001824	Weight loss
HP:0001945	Fever

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000157_5	Celiac disease	3.000000e-07
GCST000612_32	Celiac disease	3.000000e-17
GCST001804_1	Behcet’s disease	4.000000e-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
GCST004133_35	Ulcerative colitis	2.000000e-06
GCST005523_15	Celiac disease	9.000000e-09
GCST005528_28	Juvenile idiopathic arthritis (oligoarticular or rheumatoid factor-negative polyarticular)	2.000000e-07
GCST006979_63	Heel bone mineral density	1.000000e-11
GCST008644_24	Celiac disease and Rheumatoid arthritis	2.000000e-11
GCST009874_10	Celiac disease	2.000000e-19
GCST011365_122	Myocardial infarction	2.000000e-06
GCST90010715_7	Arthritis (juvenile idiopathic)	3.000000e-11
GCST90011899_121	Aspartate aminotransferase levels	3.000000e-09

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009270	heel bone mineral density
EFO:0004736	aspartate aminotransferase measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2413 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 14,302 (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
CHEMBL2205807	ABAMETAPIR	4	748
CHEMBL254316	RALTEGRAVIR	4	12,743
CHEMBL2178570	AZD4818	2	127
CHEMBL232656	BX 471 FREE BASE	2	191
CHEMBL3334824	BMS-817399	2	16
CHEMBL4444976	CCX354	2	381
CHEMBL535607	BX 471	2	77
CHEMBL4456123	BI 639667	1	19

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 (22 total), top 22:

Ligand	Action	Affinity	Parameter
CCL3	Full agonist	10.2	pKi
[125I]CCL2 (human)	Full agonist	9.4	pKd
[125I]CCL7 (human)	Full agonist	9.2	pKd
MLN-3897	Antagonist	9.1	pIC50
BX 471	Antagonist	9.0	pKi
BMS-817399	Antagonist	9.0	pIC50
CCL23	Full agonist	8.9	pKi
BP-CCL3	Full agonist	8.8	pKi
[125I]CCL3 (human)	Full agonist	8.8	pKd
compound 2b-1 [PMID: 12614873]	Antagonist	8.7	pIC50
[125I]CCL8 (human)	Full agonist	8.3	pKd
CCL5	Full agonist	8.2	pKi
[125I]CCL5 (human)	Full agonist	8.2	pKd
CCL7	Full agonist	8.1	pKi
vMIP-II	Antagonist	8.1	pIC50
UCB35625	Antagonist	8.02	pIC50
CP-481,715	Antagonist	8.0	pKd
CCL15	Full agonist	7.9	pIC50
CCL4	Antagonist	7.8	pKi
CCL14	Full agonist	7.4	pKi
Flu-CCL3	Full agonist	7.1	pKi
CCL18	Antagonist	6.1	pIC50

Binding affinities (BindingDB)

29 measured of 29 human assays (29 total across all organisms); most potent 29 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-propan-2-ylurea	KI	0.5 nM	US-8633226: Piperidinyl derivative as a modulator of chemokine receptor activity
1-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-3-[(2S)-3-hydroxy-3-methylbutan-2-yl]urea	IC50	0.7 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]cyclopentanecarboxamide	KI	0.7 nM	US-8633226: Piperidinyl derivative as a modulator of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]-3-sulfamoylbenzamide	IC50	1 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]cyclopentanecarboxamide	IC50	1.3 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
cis-(1S,3R)-N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]-3-hydroxycyclopentane-1-carboxamide	IC50	1.5 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
3-[[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]carbamoyl]benzoic acid	IC50	1.6 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
3-N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]benzene-1,3-dicarboxamide	IC50	1.8 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]benzamide	IC50	2.1 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
1-[(2R)-butan-2-yl]-3-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]urea	KI	2.1 nM	US-8633226: Piperidinyl derivative as a modulator of chemokine receptor activity
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-methylbutanamide	KI	2.6 nM	US-8633226: Piperidinyl derivative as a modulator of chemokine receptor activity
CHEMBL2398749	IC50	2.6 nM
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-hydroxy-3-methylbutanamide	KI	3.7 nM	US-8633226: Piperidinyl derivative as a modulator of chemokine receptor activity
3-[[(1R,2S)-2-[(4S)-4-hydroxy-4-(4-isocyanophenyl)-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]carbamoyl]benzoic acid	IC50	11.3 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
1-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]-3-phenylurea	IC50	11.5 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
tert-butyl N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]carbamate	IC50	12.1 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
cis-(1R,3S)-N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclopentyl]-3-hydroxycyclopentane-1-carboxamide	IC50	14 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
1-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-3-[(2R)-2-hydroxypropyl]urea	IC50	14.6 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-3-phenylpropanamide	IC50	15.7 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]-4-oxocyclohexyl]benzamide	IC50	17.2 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
1-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-3-phenylurea	IC50	18.5 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]pyrimidine-5-carboxamide	IC50	18.7 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
(2S)-N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-2-hydroxy-2-phenylacetamide	IC50	581 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-2-hydroxyacetamide	IC50	768 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]-1-methylcyclohexyl]benzamide	IC50	818 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
(2R)-N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-2-hydroxy-2-phenylacetamide	IC50	858 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]-3-piperidin-1-ylpropanamide	IC50	932 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
methyl N-[(1R,2S)-2-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]cyclohexyl]carbamate	IC50	997 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity
N-[(7S,8R)-7-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidine-1-carbonyl]-1,4-dioxaspiro[4.5]decan-8-yl]benzamide	IC50	1060 nM	US-8536198: Piperidine derivatives as modulators of chemokine receptor activity

ChEMBL bioactivities

1141 potent at pChembl≥5 of 1174 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.37	Ki	0.043	nM	CHEMBL519240
10.09	IC50	0.081	nM	CHEMBL4128926
10.06	IC50	0.087	nM	CHEMBL519240
10.00	IC50	0.1	nM	CHEMBL197375
9.82	ED50	0.15	nM	CHEMBL513863
9.70	IC50	0.2	nM	CHEMBL4464625
9.70	IC50	0.2	nM	CHEMBL4457209
9.52	IC50	0.3	nM	CHEMBL4475581
9.52	IC50	0.3	nM	CHEMBL4464625
9.44	IC50	0.36	nM	CHEMBL2332935
9.44	IC50	0.36	nM	CHEMBL2332933
9.40	IC50	0.4	nM	BX 471
9.30	Ki	0.5	nM	CHEMBL3656279
9.28	IC50	0.52	nM	CHEMBL2332936
9.20	IC50	0.63	nM	CHEMBL3099947
9.19	IC50	0.64	nM	CHEMBL2332931
9.15	IC50	0.7	nM	CHEMBL3679659
9.15	Ki	0.7	nM	CHEMBL2398747
9.14	IC50	0.73	nM	CHEMBL277930
9.10	IC50	0.8	nM	CHEMBL2322875
9.10	IC50	0.79	nM	CHEMBL2332940
9.10	IC50	0.8	nM	CHEMBL2398729
9.10	IC50	0.8	nM	CHEMBL2398726
9.10	IC50	0.8	nM	CHEMBL4571977
9.05	IC50	0.9	nM	CHEMBL277930
9.05	IC50	0.9	nM	CHEMBL2332930
9.05	IC50	0.9	nM	CHEMBL331897
9.05	IC50	0.89	nM	CHEMBL3099945
9.05	IC50	0.9	nM	CHEMBL196860
9.04	IC50	0.92	nM	CHEMBL2391803
9.02	IC50	0.96	nM	CHEMBL2332934
9.02	IC50	0.96	nM	CHEMBL2332932
9.00	Kd	1	nM	BX 471 FREE BASE
9.00	Ki	1	nM	BX 471 FREE BASE
9.00	IC50	1	nM	CHEMBL2398717
9.00	IC50	1	nM	CHEMBL2398726
9.00	IC50	1	nM	CHEMBL3334818
9.00	IC50	1	nM	BMS-817399
9.00	IC50	1	nM	CHEMBL198949
9.00	IC50	1	nM	CHEMBL197345
9.00	IC50	1	nM	CHEMBL372807
9.00	IC50	1	nM	CHEMBL3679651
9.00	IC50	1	nM	CHEMBL4464625
9.00	IC50	1	nM	CHEMBL66159
8.96	IC50	1.1	nM	CHEMBL2391810
8.96	IC50	1.1	nM	CHEMBL2398728
8.96	IC50	1.1	nM	BX 471 FREE BASE
8.92	IC50	1.2	nM	CHEMBL2398744
8.92	IC50	1.2	nM	CHEMBL2398769
8.92	IC50	1.2	nM	CHEMBL4518015

PubChem BioAssay actives

1075 with measured affinity, of 1637 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
(7aS,11aS)-4-piperazin-1-yl-5,6,7a,8,9,10,11,11a-octahydro-[1]benzofuro[2,3-h]quinazolin-2-amine	346424: Displacement of radiolabeled MIP1alpha from human CCR1 receptor	ki	<0.0001	uM
N-[5-chloro-2-[(E)-3-[(2R,5S)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-3-oxoprop-1-enyl]phenyl]acetamide	257008: Antagonistic activity at human CCR1 by inhibition of MIP-1alpha induced calcium mobilization in THP1 cells	ic50	0.0001	uM
3-[[5-[4-(tert-butylsulfamoyl)naphthalen-1-yl]-4-(cyclohexylmethyl)-1,3-thiazole-2-carbonyl]amino]cyclobutane-1-carboxylic acid	1494746: Displacement of [125I]MIP-1alpha from human recombinant CCR1 receptor after 120 mins by scintillation counting analysis	ic50	0.0001	uM
1-(4-fluorophenyl)-N-[(1S)-1-(2-methylsulfonyl-4-pyridinyl)propyl]pyrazolo[5,4-c]pyridine-4-carboxamide	1535353: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay	ic50	0.0002	uM
1-(4-fluorophenyl)-N-[1-(2-methylsulfonyl-4-pyridinyl)propyl]pyrazolo[5,4-c]pyridine-4-carboxamide	1535353: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay	ic50	0.0002	uM
1-(4-fluorophenyl)-N-[1-(2-methylsulfonyl-4-pyridinyl)butyl]pyrazolo[5,4-c]pyridine-4-carboxamide	1535353: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay	ic50	0.0003	uM
N-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0004	uM
[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)methyl]-2-methylpiperazin-1-yl]-2-oxoethoxy]phenyl]urea;hydrochloride	257008: Antagonistic activity at human CCR1 by inhibition of MIP-1alpha induced calcium mobilization in THP1 cells	ic50	0.0004	uM
N-[4-fluoro-2-[(2S)-3-(5-fluorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]phenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0004	uM
N-[2-[(2S)-3-(5-fluorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0005	uM
N-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-fluorophenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0006	uM
1-cyclopropyl-3-[2-[(2S)-3-(5-fluorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]urea	1061713: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cell membranes after 1.5 hrs by microbeta counting analysis	ic50	0.0006	uM
2,7-dichloro-N-[1-[[(1E)-cycloocten-1-yl]methyl]-1-ethylpiperidin-1-ium-4-yl]-9H-xanthene-9-carboxamide iodide	223366: Inhibitory activity against MIP-1 alpha- induced [Ca2+] response in U937 cells expressing human CCR1 receptor	ic50	0.0007	uM
1-[4-(4-chloro-3-methoxyphenyl)piperazin-1-yl]-2-[4-chloro-5-methyl-3-(trifluoromethyl)pyrazol-1-yl]ethanone	727725: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of CCL5/RANTES-induced chemotaxis	ic50	0.0008	uM
cis-(1R,3S)-N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-hydroxycyclopentane-1-carboxamide	755614: Binding affinity to human CCR1	ic50	0.0008	uM
trans-(1R,3R)-N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-hydroxycyclopentane-1-carboxamide	755614: Binding affinity to human CCR1	ic50	0.0008	uM
(4S)-4-(4-chlorophenyl)-1-[(3Z)-3-[9-(2-hydroxypropan-2-yl)-5H-[1]benzoxepino[3,4-b]pyridin-11-ylidene]propyl]-3,3-dimethylpiperidin-4-ol	1573704: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay	ic50	0.0008	uM
N-[2-[(2S)-2-amino-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)propoxy]-4-hydroxyphenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0008	uM
[5-chloro-2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]-[(3S)-3-hydroxypyrrolidin-1-yl]methanone	753369: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of MIP-1alpha-induced chemotaxis after 2 hrs by fluorescence assay	ic50	0.0009	uM
N-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-methoxyphenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0009	uM
2,7-dichloro-N-[1-[[(1E)-cycloocten-1-yl]methyl]-1-ethylpiperidin-1-ium-4-yl]-9H-xanthene-9-carboxamide	44611: Binding affinity towards C-C chemokine receptor type 1	ic50	0.0009	uM
1-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]-3-cyclopropylurea	1061713: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cell membranes after 1.5 hrs by microbeta counting analysis	ic50	0.0009	uM
[5-chloro-2-[(E)-3-[(2R)-4-[(4-fluorophenyl)methyl]-2-methylpiperazin-1-yl]-3-oxoprop-1-enyl]phenyl]urea	257008: Antagonistic activity at human CCR1 by inhibition of MIP-1alpha induced calcium mobilization in THP1 cells	ic50	0.0009	uM
N-[5-chloro-2-[(E)-3-[(2S,5R)-4-[(4-fluorophenyl)methyl]-2,5-dimethylpiperazin-1-yl]-3-oxoprop-1-enyl]phenyl]acetamide	257008: Antagonistic activity at human CCR1 by inhibition of MIP-1alpha induced calcium mobilization in THP1 cells	ic50	0.0010	uM
N-[2-[(2S)-3-(5-fluorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]phenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0010	uM
N-[5-chloro-2-[(E)-3-[(2R)-4-[(4-fluorophenyl)methyl]-2-methylpiperazin-1-yl]-3-oxoprop-1-enyl]phenyl]acetamide	257008: Antagonistic activity at human CCR1 by inhibition of MIP-1alpha induced calcium mobilization in THP1 cells	ic50	0.0010	uM
N-[(2S,3S)-8-fluoro-5-(hydrazinecarbonyl)-3-hydroxy-8-methyl-1-phenylnonan-2-yl]quinoxaline-2-carboxamide	89636: Inhibition of CCL3 induced chemotaxis in human T lymphocytes	ic50	0.0010	uM
N-[5-chloro-2-[(E)-3-[3-[(4-fluorophenyl)methyl]-3,8-diazabicyclo[3.2.1]octan-8-yl]-3-oxoprop-1-enyl]-4-methoxyphenyl]acetamide	257006: Antagonistic activity at rat CCR1 in CHO-K1 cells	ic50	0.0010	uM
1-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-(2-hydroxy-2-methylpropyl)urea	1186890: Displacement of [125I]MIP-1alpha from CCR1 in human THP1 cells	ic50	0.0010	uM
[5-chloro-2-[2-[(2R)-4-[(4-fluorophenyl)methyl]-2-methylpiperazin-1-yl]-2-oxoethoxy]phenyl]urea	707902: Binding affinity to human CCR1 by radioligand binding assay	kd	0.0010	uM
1-benzyl-3-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]urea	1186890: Displacement of [125I]MIP-1alpha from CCR1 in human THP1 cells	ic50	0.0010	uM
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-cyclopropylacetamide	755614: Binding affinity to human CCR1	ic50	0.0010	uM
N-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]phenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0010	uM
cis-(1S,3R)-N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-3-hydroxycyclopentane-1-carboxamide	755613: Antagonist activity at human CCR1 assessed as inhibition of MIP1alpha-induced chemotaxis	ic50	0.0011	uM
[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]-(4-hydroxypiperidin-1-yl)methanone	753369: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of MIP-1alpha-induced chemotaxis after 2 hrs by fluorescence assay	ic50	0.0011	uM
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-4-methylpentanamide	755613: Antagonist activity at human CCR1 assessed as inhibition of MIP1alpha-induced chemotaxis	ic50	0.0012	uM
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-2-pyridin-4-ylacetamide	755614: Binding affinity to human CCR1	ic50	0.0012	uM
1-(4-fluorophenyl)-N-[[3-methylsulfonyl-5-(trifluoromethyl)phenyl]methyl]pyrazolo[5,4-c]pyridine-4-carboxamide	1535353: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay	ic50	0.0012	uM
[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]-[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methanone	753369: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of MIP-1alpha-induced chemotaxis after 2 hrs by fluorescence assay	ic50	0.0013	uM
1-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]-3-methylurea	1061713: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cell membranes after 1.5 hrs by microbeta counting analysis	ic50	0.0013	uM
2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-N-cyclopropyl-4-hydroxybenzamide	753369: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of MIP-1alpha-induced chemotaxis after 2 hrs by fluorescence assay	ic50	0.0014	uM
2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-N-cyclopropyl-4-fluorobenzamide	753369: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of MIP-1alpha-induced chemotaxis after 2 hrs by fluorescence assay	ic50	0.0014	uM
N-[2-[(2S)-2-amino-3-(5-fluorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)propoxy]-4-hydroxyphenyl]acetamide	730803: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cells after 1.5 hrs	ic50	0.0014	uM
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]cyclopentanecarboxamide	755614: Binding affinity to human CCR1	ic50	0.0014	uM
1-(4-fluorophenyl)-N-[1-(2-methylsulfonyl-4-pyridinyl)ethyl]pyrazolo[5,4-c]pyridine-4-carboxamide	1535353: Antagonist activity at recombinant CCR1 (unknown origin) expressed in non-adherent cells co-expressing Galpha16 assessed as inhibition of MIP-1 alpha-induced calcium flux by Fluo-4 NW or Calcium 4 dye based FLIPR TETRA assay	ic50	0.0014	uM
N-[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]phenyl]pyrrolidine-1-carboxamide	1061713: Displacement of [125I]MIP-1alpha from human recombinant CCR1 expressed in HEK293 cell membranes after 1.5 hrs by microbeta counting analysis	ic50	0.0014	uM
N-[5-chloro-2-[(E)-3-[(2R)-4-[(4-fluorophenyl)methyl]-2-methylpiperazin-1-yl]-3-oxoprop-1-enyl]-4-methoxyphenyl]acetamide	257008: Antagonistic activity at human CCR1 by inhibition of MIP-1alpha induced calcium mobilization in THP1 cells	ic50	0.0015	uM
N-[(2R)-1-[(4S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl]-3-methyl-1-oxobutan-2-yl]-4-phenylbutanamide	755614: Binding affinity to human CCR1	ic50	0.0017	uM
[2-[(2S)-3-(5-chlorospiro[3H-1-benzofuran-2,4’-piperidine]-1’-yl)-2-hydroxypropoxy]-4-hydroxyphenyl]-pyrrolidin-1-ylmethanone	753369: Antagonist activity at CCR1 in human THP1 cells assessed as inhibition of MIP-1alpha-induced chemotaxis after 2 hrs by fluorescence assay	ic50	0.0018	uM
2-[3-(aminomethyl)piperidine-1-carbonyl]-N-[1-[[(1E)-cyclononen-1-yl]methyl]piperidin-4-yl]-9H-xanthene-9-carboxamide	707909: Binding affinity to CCR1	ki	0.0018	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
Tretinoin	increases expression, affects cotreatment	4
Valproic Acid	affects cotreatment, increases expression	4
Arsenic	affects expression, affects cotreatment, decreases expression	2
Benzo(a)pyrene	increases expression, increases mutagenesis	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
GSK-J4	decreases expression	1
ammonium 2,3,3,3-tetrafluoro-2-(heptafluoropropoxy)-propanoate	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
testosterone enanthate	affects expression	1
triphenyl phosphate	affects expression	1
sodium bichromate	decreases expression	1
4-hydroxy-2-nonenal	decreases expression	1
3,4,3’,4’-tetrachlorobiphenyl	affects expression	1
nickel sulfate	affects expression	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	increases expression	1
fumonisin B1	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Irinotecan	increases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Acetaminophen	decreases expression	1
Cannabinoids	decreases reaction, increases abundance, decreases expression	1

ChEMBL screening assays

243 unique, capped per target: 176 binding, 67 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000173	Binding	Binding affinity to CCR1	Synthesis and evaluation of dibenzothiazepines: a novel class of selective cannabinoid-1 receptor inverse agonists. — J Med Chem
CHEMBL1055684	Functional	Inhibition of human CCR1 expressed in mouse B300-19 cells assessed as inhibition of RANTES-induced calcium flux at 10 uM	Synthesis, biological evaluation, and metabolic stability of acrylamide derivatives as novel CCR3 antagonists. — Bioorg Med Chem

Cellosaurus cell lines

13 cell lines: 8 cancer cell line, 4 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1D94	HOS-CD4-CCR1	Cancer cell line	Female
CVCL_1E06	GHOST(3).CCR1	Cancer cell line	Female
CVCL_D1VL	Abcam A-549 CCR1 KO	Cancer cell line	Male
CVCL_D2A6	Abcam HCT 116 CCR1 KO	Cancer cell line	Male
CVCL_E4JX	HEK293 CCR1	Transformed cell line	Female
CVCL_KA12	CHO-K1/Galpha15/CCR1	Spontaneously immortalized cell line	Female
CVCL_KU87	cAMP Hunter CHO-K1 CCR1 Gi	Spontaneously immortalized cell line	Female
CVCL_KW55	PathHunter CHO-K1 CCR1 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_KZ90	PathHunter U2OS CCR1 Activated GPCR Internalization	Cancer cell line	Female
CVCL_KZ91	PathHunter U2OS CCR1 beta-arrestin-1	Cancer cell line	Female

Clinical trials (associated diseases)

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