CCR5

Summary

CCR5 (C-C motif chemokine receptor 5, HGNC:1606) is a protein-coding gene on chromosome 3p21.31, encoding C-C chemokine receptor type 5 (P51681). Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level.

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. This protein is expressed by T cells and macrophages, and is known to be an important co-receptor for macrophage-tropic virus, including HIV, to enter host cells. Defective alleles of this gene have been associated with the HIV infection resistance. The ligands of this receptor include monocyte chemoattractant protein 2 (MCP-2), macrophage inflammatory protein 1 alpha (MIP-1 alpha), macrophage inflammatory protein 1 beta (MIP-1 beta) and regulated on activation normal T expressed and secreted protein (RANTES). Expression of this gene was also detected in a promyeloblastic cell line, suggesting that this protein may play a role in granulocyte lineage proliferation and differentiation. This gene is located at the chemokine receptor gene cluster region. An allelic polymorphism in this gene results in both functional and non-functional alleles; the reference genome represents the functional allele. Two transcript variants encoding the same protein have been found for this gene.

Source: NCBI Gene 1234 — RefSeq curated summary.

At a glance

• GWAS associations: 9
• Clinical variants (ClinVar): 45 total
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001394783

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1606
Approved symbol	CCR5
Name	C-C motif chemokine receptor 5
Location	3p21.31
Locus type	gene with protein product
Status	Approved
Aliases	CKR-5, CC-CKR-5, CKR5, CD195, IDDM22
Ensembl gene	ENSG00000160791
Ensembl biotype	protein_coding
OMIM	601373
Entrez	1234

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000292303, ENST00000445772

RefSeq mRNA: 3 — MANE Select: NM_001394783 NM_000579, NM_001100168, NM_001394783

CCDS: CCDS2739

Canonical transcript exons

ENST00000292303 — 2 exons

Exon	Start	End
ENSE00001054508	46372892	46376206
ENSE00001078626	46370946	46370988

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 89.38.

FANTOM5 (CAGE): breadth broad, TPM avg 6.3603 / max 277.3082, expressed in 355 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
36451	4.6010	327
36450	1.7592	253

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	89.38	gold quality
olfactory bulb	UBERON:0002264	89.07	gold quality
epithelium of nasopharynx	UBERON:0001951	87.90	gold quality
nasopharynx	UBERON:0001728	87.89	gold quality
diaphragm	UBERON:0001103	87.25	gold quality
parietal pleura	UBERON:0002400	85.81	gold quality
pleura	UBERON:0000977	85.74	gold quality
visceral pleura	UBERON:0002401	85.28	gold quality
palpebral conjunctiva	UBERON:0001812	84.50	gold quality
granulocyte	CL:0000094	84.48	gold quality
germinal epithelium of ovary	UBERON:0001304	83.66	gold quality
mucosa of urinary bladder	UBERON:0001259	83.58	silver quality
vermiform appendix	UBERON:0001154	83.43	gold quality
superficial temporal artery	UBERON:0001614	82.00	gold quality
jejunal mucosa	UBERON:0000399	81.66	gold quality
lymph node	UBERON:0000029	81.43	gold quality
leukocyte	CL:0000738	80.23	gold quality
left ventricle myocardium	UBERON:0006566	80.17	gold quality
caecum	UBERON:0001153	79.85	gold quality
decidua	UBERON:0002450	79.82	gold quality
mononuclear cell	CL:0000842	79.54	gold quality
monocyte	CL:0000576	79.25	gold quality
epithelial cell of pancreas	CL:0000083	78.61	silver quality
amniotic fluid	UBERON:0000173	78.58	gold quality
oral cavity	UBERON:0000167	78.45	gold quality
cardiac muscle of right atrium	UBERON:0003379	78.31	gold quality
blood	UBERON:0000178	78.19	gold quality
eye	UBERON:0000970	77.96	gold quality
myocardium	UBERON:0002349	77.27	gold quality
colonic epithelium	UBERON:0000397	76.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.72

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, CEBPB, CREB1, EGR1, FOS, GATA1, GATA3, HAND1, IRF1, JUN, KLF2, MYC, NFKB1, NR3C2, POU2F2, RELA, STAT1, STAT3, TRERF1, YY1

miRNA regulators (miRDB)

65 targeting CCR5, 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-5193	100.00	67.26	1744
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-629-3P	99.85	67.99	1875
HSA-MIR-636	99.80	69.58	1500
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-8084	99.73	69.57	1760
HSA-MIR-4524A-3P	99.72	66.85	2406
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-12123	99.52	71.79	2990
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-125B-5P	99.36	70.36	1662
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-4312	99.34	67.30	511
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6731-5P	99.28	67.42	2375

Literature-anchored findings (GeneRIF, showing 40)

• Biological characterization and chemokine receptor usage of HIV type 1 isolates prevalent in Brazil. (PMID:11559423)
• differences in primary structural requirements for RANTES, MIP-1 alpha, and vMIP-II binding (PMID:11700073)
• Association of CCR5 genotype with disease progression of HIV infection (PMID:11709782)
• Effect of cocaine on chemokine and CCR-5 gene expression by mononuclear cells from normal donors and HIV-1 infected patients. (PMID:11727771)
• Up-regulation on distinct subpopulations of antigen-activated CD4+ T lymphocytes (PMID:11751947)
• 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)
• CC chemokine receptor 5 (CCR5) mRNA expression in pulmonary sarcoidosis (PMID:11803051)
• results support the conclusion that the CCR5-Delta32/Delta32 genotype mediated resistance is incomplete and is associated with acquisition of exclusively-X4 variants of HIV-1 (PMID:11873082)
• CXCR-4 was constitutively expressed by thymocytes and it mediated polarization, migration and intercellular CA2+ increase in response to SDF-1. (PMID:11876757)
• the role of CD4, CXCR4, and CCR5 in HIV envelope-mediated apoptosis was examined in peripheral blood mononuclear cells (PMID:11878912)
• cytokine regulation of CCR5 expression on monocytes, monocyte-derived macrophages (MDMs), and microglia was investigated (PMID:11920312)
• Lipopolysaccharide,lipoarabinomannan and lipoteichoic acid down-regulated the expression of CXCR4 and CCR5 on monocytes (PMID:11920324)
• Results identified specific regions in CCR5 that confer HIV-1 coreceptor function, structural rearrangements in the transmembrane region that may modulate this activity, and a role for the extracellular surface in folding and assembly. (PMID:11937056)
• Graves’ disease is associated with an altered CCR5 expression in thyroid-derived compared to peripheral blood t lymphocytes (PMID:11966764)
• Elevated expression of CCR5 by myeloid (CD11c+) blood dendritic cells in multiple sclerosis and acute optic neuritis (PMID:11966770)
• High level expression of CCR5 is a characteristic and selective feature of circulating V delta 2 gamma delta T cells, which is in line with their suspected function as Th1 effector T cells. (PMID:11994442)
• CCR5 and CXCR4 are present on the resident testicular macrophages in the interstitial space but not in the germ cell line (PMID:11994538)
• Cholesterol is essential for macrophage inflammatory protein 1 beta binding and signaling and conformational integrity of CC chemokine receptor 5. (PMID:12036855)
• Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C. (PMID:12055576)
• decreased density of the CCR5 receptor on the surface of CD4+ lymphocytes and monocytes/macrophages is associated with the CCR5-59653T transition in the promoter region (PMID:12056598)
• 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)
• 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)
• Caco-2 and M cells do not express CCR5, but transfection of these cells with CCR5 cDNA restores transport of R5 virus, which demonstrates that HIV-1 transport across M cells is receptor-mediated. (PMID:12093918)
• CCR5 mediates Fas- and caspase-8 dependent apoptosis of both uninfected and HIV infected primary human CD4 T cells (PMID:12131184)
• Data show that two distinct forms of CCR5 protein, 62 and 42k Da, are present in lymphocytic cells. (PMID:12163044)
• tyrosine sulfastion of n-terminal peptide follows a discrete pattern and temporal sequence (PMID:12169668)
• expression detected in a stromal cell line, a myeloma cell line, and primary multiple myeloma cells and may be target for MIP1A and MIP1B. (PMID:12200385)
• prevalence of CCR5-Delta32 allele frequency in a large Pakistani population sample representing 10 ethnic groups (PMID:12215252)
• Binding chemokines modulate CXCL12 (SDF-1)-induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor (PMID:12239139)
• P. falciparum antigens (PF-Ags) variably regulate the expression of HIV-1 coreceptors and modulate the infectability of CD4 cells by HIV-1 (PMID:12355376)
• Significant increase in surface CCR5 in CD4+, CD8+, CD19+ and CD14+ cells as well as an increased percentage of CXCR3 and CXCR4 in CD14+ cells in MS patients. (PMID:12356205)
• role of IL-12 and IFN-gamma on inducing inflammatory chemokine secretion and down-regulating CCR5 expression in human T cells (PMID:12377943)
• influence of the major CCR5 promoter or coding region variants as haplotypes and genotypes in a cohort of 250 chronically infected HCV patients (PMID:12403355)
• CCR5 is phosphorylated at specific sites by protein kinase C and GPCR kinase (PMID:12403770)
• These results suggest that oligomerization of chemokine receptor CCR5 and opioid receptors mu, delta and kappa on the cell membrane of human or monkey lymphocytes may modulate receptor functions. (PMID:12413885)
• chemokine receptor CCR5 deletion mutation is associated with multiple sclerosis in HLA-DR4-positive Russians (PMID:12451219)
• META-ANALYSIS: Effect of CCR5-delta32 heterozygosity on the risk of perinatal HIV-1 infection (PMID:12514416)
• An increase in the numbers of CCR5(+) cells in H. pylori-infected stomach mucosa suggests that this molecule may play an important role in gastric immune responses. (PMID:12522035)
• physical association of CD4 and CCR5 results in receptor cross-talk with allosteric CD4-dependent regulation of the binding and signaling properties of CCR5 (PMID:12531905)
• Limited protective effect of the CCR5Delta32/CCR5Delta32 genotype on human immunodeficiency virus infection incidence in a cohort of patients with hemophilia and selection for genotypic X4 virus (PMID:12552446)

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	Ccr5	ENSMUSG00000079227
rattus_norvegicus	Ccr5	ENSRNOG00000049115

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), 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 5 — P51681 (reviewed: P51681)

Alternative names: CHEMR13, HIV-1 fusion coreceptor

All UniProt accessions (2): P51681, Q38L21

UniProt curated annotations — full annotation on UniProt →

Function. Receptor for a number of inflammatory CC-chemokines including CCL3/MIP-1-alpha, CCL4/MIP-1-beta and RANTES and subsequently transduces a signal by increasing the intracellular calcium ion level. May play a role in the control of granulocytic lineage proliferation or differentiation. Participates in T-lymphocyte migration to the infection site by acting as a chemotactic receptor. (Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) of human immunodeficiency virus-1/HIV-1.

Subunit / interactions. Interacts with PRAF2. Efficient ligand binding to CCL3/MIP-1alpha and CCL4/MIP-1beta requires sulfation, O-glycosylation and sialic acid modifications. Glycosylation on Ser-6 is required for efficient binding of CCL4. Interacts with GRK2. Interacts with ARRB1 and ARRB2. Interacts with CNIH4. Interacts with S100A4; this interaction stimulates T-lymphocyte chemotaxis. (Microbial infection) Interacts with HIV-1 surface protein gp120. (Microbial infection) May interact with human cytomegalovirus/HHV-5 protein UL78. (Microbial infection) Interacts with Kaposi virus protein vCCL2.

Subcellular location. Cell membrane.

Tissue specificity. Highly expressed in spleen, thymus, in the myeloid cell line THP-1, in the promyeloblastic cell line KG-1a and on CD4+ and CD8+ T-cells. Medium levels in peripheral blood leukocytes and in small intestine. Low levels in ovary and lung.

Post-translational modifications. Sulfated on at least 2 of the N-terminal tyrosines. Sulfation contributes to the efficiency of HIV-1 entry and is required for efficient binding of the chemokines, CCL3 and CCL4. O-glycosylated, but not N-glycosylated. Ser-6 appears to be the major site even if Ser-7 may be also O-glycosylated. Also sialylated glycans present which contribute to chemokine binding. Thr-16 and Ser-17 may also be glycosylated and, if so, with small moieties such as a T-antigen. Palmitoylation in the C-terminal is important for cell surface expression, and to a lesser extent, for HIV entry. Phosphorylation on serine residues in the C-terminal is stimulated by binding CC chemokines especially by APO-RANTES.

Disease relevance. Type 1 diabetes mellitus 22 (T1D22) [MIM:612522] A multifactorial disorder of glucose homeostasis that is characterized by susceptibility to ketoacidosis in the absence of insulin therapy. Clinical features are polydipsia, polyphagia and polyuria which result from hyperglycemia-induced osmotic diuresis and secondary thirst. These derangements result in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Induction. (Microbial infection) May be down-regulated by human cytomegalovirus/HHV-5 protein UL78.

Polymorphism. Variations in CCR5 are associated with resistance or susceptibility to immunodeficiency virus type 1 (resistance or susceptibility to HIV-1) [MIM:609423]. Variations in CCR5 gene also influence the rate of progression to AIDS after infection. Variations in CCR5 are associated with susceptibility to West Nile virus (WNV) infection [MIM:610379].

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

RefSeq proteins (3): NP_000570, NP_001093638, NP_001381712* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR000355	Chemokine_rcpt	Family
IPR002240	Chemokine_CCR5	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR050119	CCR1-9-like	Family

Pfam: PF00001

UniProt features (113 total): sequence variant 38, mutagenesis site 22, helix 15, topological domain 8, modified residue 8, transmembrane region 7, turn 4, strand 3, lipid moiety-binding region 3, glycosylation site 2, disulfide bond 2, chain 1

Structure

Experimental structures (PDB)

26 structures.

PDB	Method	Resolution (Å)
5YD3	X-RAY DIFFRACTION	1.35
5YD4	X-RAY DIFFRACTION	1.35
5YY4	X-RAY DIFFRACTION	1.59
9J8A	X-RAY DIFFRACTION	1.75
5YD5	X-RAY DIFFRACTION	1.96
5UIW	X-RAY DIFFRACTION	2.2
7F1T	X-RAY DIFFRACTION	2.6
4MBS	X-RAY DIFFRACTION	2.71
6AKX	X-RAY DIFFRACTION	2.8
6AKY	X-RAY DIFFRACTION	2.8
7F1S	ELECTRON MICROSCOPY	2.8
7F1Q	ELECTRON MICROSCOPY	2.9
7F1R	ELECTRON MICROSCOPY	3
7O7F	ELECTRON MICROSCOPY	3.15
7NJZ	X-RAY DIFFRACTION	3.2
8AS2	X-RAY DIFFRACTION	3.2
9WP1	X-RAY DIFFRACTION	3.2
7NW3	X-RAY DIFFRACTION	3.2
8AS3	X-RAY DIFFRACTION	3.5
6MEO	ELECTRON MICROSCOPY	3.9
6MET	ELECTRON MICROSCOPY	4.5
2L87	SOLUTION NMR
2MZX	SOLUTION NMR
2RLL	SOLUTION NMR
2RRS	SOLUTION NMR
6FGP	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51681-F1	85.41	0.66

Antibody-complex structures (SAbDab): 10 — 5YD3, 5YD4, 5YD5, 5YY4, 7NJZ, 7NW3, 7O7F, 8AS2, 8AS3, 9J8A

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 (11): 3, 10, 14, 15, 336, 337, 342, 349, 321, 323, 324

Disulfide bonds (2): 20–269, 101–178

Glycosylation sites (2): 6, 7

Mutagenesis-validated functional residues (22):

Position	Phenotype
3	no sulfation and strongly decreases binding with ccl4 and ccl5; when associated with d-10; d-14 and d-15. restores most
3	no sulfation and strongly decreases binding with ccl4 and ccl5; when associated with f-10; f-14 and f-15.
6–7	loss of molecular mass of 2 kda compared to wild type when treated with o-glycosidase. dramatically reduces binding with
6	strongly decreases ccl4 binding. no change in glycosylation status.
7	no change in glycosylation status and binds ccl4 as efficiently as wild type.
10	no sulfation and greatly decreases binding of ccl4 and ccl5; when associated with f-3; f-14 and f-15. small loss of sulf
14	no sulfation and greatly decreased binding of ccl4 and ccl5; when associated with d-3; d-10 and d-14. no restoration of
14	no sulfation and greatly decreases binding of ccl4 and ccl5; when associated with f-3; f-10; and f-15. small loss of sul
15	no sulfation and greatly decreased binding of ccl4 and ccl5; when associated with d-3; d-10 and d-14. restored most ccl4
15	no sulfation and greatly decreases binding of ccl4 and ccl5; when associated with f-3; f-10 and f-14. small loss of sulf
16–17	similar decrease in molecular mass when treated with o-glycosidase as for wild type. loss of molecular mass of about 2 k
20	decreases to 40% surface expression. no effect on conformational integrity. disrupts binding of ccl4. decreases cell hiv
101	decreases to 40% surface expression. disrupts conformational integrity. disrupts binding of ccl4. decreases hiv cell inf
178	decreases to 40% surface expression. disrupts conformational integrity. disrupts binding of ccl4. decreases hiv cell inf
269	decreases to 40% surface expression. no effect on conformational integrity. disrupts binding of ccl4. decreases cell hiv
321	small reduction in palmitoylation. cell surface expression reduced by 50%. greatly reduced palmitoylation. cell surface
323	small reduction in palmitoylation. cell surface expression reduced by 50%. greatly reduced palmitoylation. cell surface
324	small reduction in palmitoylation. cell surface expression reduced by 50%. greatly reduced palmitoylation. cell surface
336	apo-rantes-stimulated phosphorylation reduced by 15%; apo-rantes-stimulated phosphorylation reduced by 30-50%; when asso
337	apo-rantes-stimulated phosphorylation reduced by 18%; apo-rantes-stimulated phosphorylation reduced by 30-50% on apo-ran
342	apo-rantes-stimulated phosphorylation reduced by 42%. phosphorylation reduced by 50% on apo-rantes stimulation; when ass
349	apo-rantes-stimulated phosphorylation reduced by 43%; apo-rantes-stimulated phosphorylation reduced by 30-50%; when asso

Function

Pathways and Gene Ontology

Reactome pathways

19 pathways

ID	Pathway
R-HSA-173107	Binding and entry of HIV virion
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-162587	HIV Life Cycle
R-HSA-162594	Early Phase of HIV Life Cycle
R-HSA-162906	HIV Infection
R-HSA-1643685	Disease
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-5663205	Infectious disease
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 383 (showing top): MODULE_92, LIANG_HEMATOPOIESIS_STEM_CELL_NUMBER_SMALL_VS_HUGE_UP, WALLACE_PROSTATE_CANCER_RACE_UP, GOBP_DENDRITIC_CELL_MIGRATION, GOBP_CELL_CHEMOTAXIS, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOBP_REGULATION_OF_LEUKOCYTE_APOPTOTIC_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, MODULE_64, KENNY_CTNNB1_TARGETS_UP, GOCC_CELL_SURFACE, MODULE_128

GO Biological Process (24): MAPK cascade (GO:0000165), dendritic cell chemotaxis (GO:0002407), calcium ion transport (GO:0006816), apoptotic process (GO:0006915), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), cellular defense response (GO:0006968), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), positive regulation of cytosolic calcium ion concentration (GO:0007204), cell-cell signaling (GO:0007267), release of sequestered calcium ion into cytosol by sarcoplasmic reticulum (GO:0014808), calcium-mediated signaling (GO:0019722), signaling (GO:0023052), cell chemotaxis (GO:0060326), response to cholesterol (GO:0070723), cellular response to lipopolysaccharide (GO:0071222), negative regulation of macrophage apoptotic process (GO:2000110), defense response (GO:0006952), signal transduction (GO:0007165), symbiont entry into host cell (GO:0046718), chemokine-mediated signaling pathway (GO:0070098), cellular response to cytokine stimulus (GO:0071345)

GO Molecular Function (11): virus receptor activity (GO:0001618), actin binding (GO:0003779), phosphatidylinositol-4,5-bisphosphate phospholipase C activity (GO:0004435), chemokine receptor activity (GO:0004950), coreceptor activity (GO:0015026), C-C chemokine receptor activity (GO:0016493), C-C chemokine binding (GO:0019957), identical protein binding (GO:0042802), chemokine (C-C motif) ligand 5 binding (GO:0071791), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515)

GO Cellular Component (6): cytoplasm (GO:0005737), endosome (GO:0005768), plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-15 pathways:

Category	Pathways
Signaling by GPCR	2
Early Phase of HIV Life Cycle	1
Peptide ligand-binding receptors	1
GPCR downstream signalling	1
Signaling by Interleukins	1
Immune System	1
HIV Infection	1
HIV Life Cycle	1
Viral Infection Pathways	1
Signal Transduction	1
GPCR ligand binding	1
Class A/1 (Rhodopsin-like receptors)	1
Cytokine Signaling in Immune system	1
Disease	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular signaling cassette	2
defense response	2
signal transduction	2
chemokine binding	2
C-C chemokine binding	2
leukocyte chemotaxis	1
dendritic cell migration	1
metal ion transport	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
response to chemical	1
taxis	1
immune system process	1
response to stimulus	1
G protein-coupled receptor activity	1
regulation of biological quality	1
cell communication	1
signaling	1
sarcoplasmic reticulum calcium ion transport	1
release of sequestered calcium ion into cytosol by endoplasmic reticulum	1
regulation of biological process	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
response to sterol	1
response to alcohol	1
response to lipopolysaccharide	1
cellular response to molecule of bacterial origin	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
negative regulation of myeloid cell apoptotic process	1
macrophage apoptotic process	1
negative regulation of leukocyte apoptotic process	1
regulation of macrophage apoptotic process	1
response to stress	1
symbiont entry into host cell	1
exogenous protein binding	1
cytoskeletal protein binding	1

Protein interactions and networks

STRING

3338 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CCR5	CD4	P01730	999
CCR5	ITIH4	Q14624	999
CCR5	CCL3	P10147	999
CCR5	CCL4	P13236	999
CCR5	CCL5	P13501	999
CCR5	CCL2	P13500	998
CCR5	CCL3L1	P16619	998
CCR5	CXCL10	P02778	997
CCR5	CCL11	P50877	996
CCR5	ERVW-1	Q9UQF0	996
CCR5	CXCL9	Q07325	995
CCR5	CXCL12	P48061	994
CCR5	CCL8	P78388	994
CCR5	CCL7	P80098	994
CCR5	CCL13	Q99616	985

IntAct

43 interactions, top by confidence:

A	B	Type	Score
CCL5	CCL5	psi-mi:“MI:0914”(association)	0.860
CCR5	CD4	psi-mi:“MI:0915”(physical association)	0.670
CXCR4	CCR5	psi-mi:“MI:0915”(physical association)	0.670
CXCR4	CCR5	psi-mi:“MI:0407”(direct interaction)	0.670
CCR5	CD4	psi-mi:“MI:0914”(association)	0.670
CCR5	CXCR4	psi-mi:“MI:0403”(colocalization)	0.670
CCR5	CCR5	psi-mi:“MI:0407”(direct interaction)	0.660
CCR5	CCL5	psi-mi:“MI:0915”(physical association)	0.660
CCR5	CCR5	psi-mi:“MI:2364”(proximity)	0.660
CCL5	CCR5	psi-mi:“MI:0407”(direct interaction)	0.660
CCR5	CCL5	psi-mi:“MI:0407”(direct interaction)	0.660
CCR5	EMP1	psi-mi:“MI:0915”(physical association)	0.560
lukE	CCR5	psi-mi:“MI:0915”(physical association)	0.540
lukE	CCR5	psi-mi:“MI:0407”(direct interaction)	0.540
CCR5	PRAF2	psi-mi:“MI:0915”(physical association)	0.520
PRAF2	CCR5	psi-mi:“MI:0915”(physical association)	0.520
CCR5	CCL17	psi-mi:“MI:0915”(physical association)	0.500
CCL17	CCR5	psi-mi:“MI:0914”(association)	0.500
ACKR1	CCR5	psi-mi:“MI:0915”(physical association)	0.470
ACKR1	CCR5	psi-mi:“MI:2364”(proximity)	0.470
CCR5	MYH9	psi-mi:“MI:0915”(physical association)	0.400
CCR5	CCL4	psi-mi:“MI:0915”(physical association)	0.400
CCR5	RAMP1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (25): CCR5 (Affinity Capture-Western), CCR5 (Two-hybrid), ARRB1 (Reconstituted Complex), CCR5 (Reconstituted Complex), CCR5 (Reconstituted Complex), CCR5 (Affinity Capture-Western), SLC20A2 (Two-hybrid), CCR5 (Reconstituted Complex), CCR5 (Affinity Capture-Western), CCR5 (Affinity Capture-Western), JAK2 (Affinity Capture-Western), STAT3 (Affinity Capture-Western), STAT5B (Affinity Capture-Western), PIK3R2 (Affinity Capture-Western), CCR5 (Reconstituted Complex)

ESM2 similar proteins: A6QNL7, O00574, O18983, O19024, O62743, O97878, O97879, O97880, O97881, O97882, O97883, O97962, P49238, P51681, P51682, P56439, P56440, P56493, P60574, P61755, P61756, P61757, P68269, P68270, Q2HJ17, Q2KTE1, Q5ECR9, Q64H34, Q6WN98, Q8HZT9, Q95NC0, Q95NC1, Q95NC2, Q95NC3, Q95NC4, Q95NC5, Q95NC6, Q95NC7, Q95NC8, Q95NC9

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

11 interactions.

A	Effect	B	Mechanism
maraviroc	down-regulates	CCR5	“chemical inhibition”
“Vicriviroc Malate”	down-regulates	CCR5	“chemical inhibition”
CCL5	“up-regulates activity”	CCR5	binding
CCL3	“up-regulates activity”	CCR5	binding
CCL4	“up-regulates activity”	CCR5	binding
CCR5	“up-regulates activity”	ERK1/2	phosphorylation
GRK3	“down-regulates activity”	CCR5	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 21 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
protein transport	6	13.9×	3e-04
immune response	5	12.4×	7e-04
inflammatory response	5	9.9×	2e-03
G protein-coupled receptor signaling pathway	5	9.5×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	29
Likely benign	4
Benign	5

Top pathogenic / likely-pathogenic (0)

SpliceAI

62 predictions. Top by Δscore:

Variant	Effect	Δscore
3:46370987:CGG:C	donor_loss	1.0000
3:46370989:G:C	donor_loss	1.0000
3:46370989:G:GG	donor_gain	1.0000
3:46370990:T:A	donor_loss	1.0000
3:46372888:ACAG:A	acceptor_gain	1.0000
3:46370984:CCCCG:C	donor_gain	0.9900
3:46370985:CCCG:C	donor_gain	0.9900
3:46370986:CCG:C	donor_gain	0.9900
3:46370987:CG:C	donor_gain	0.9900
3:46370988:GG:G	donor_gain	0.9900
3:46372890:AG:A	acceptor_gain	0.9900
3:46372891:GG:G	acceptor_gain	0.9900
3:46372887:CACAG:C	acceptor_loss	0.9800
3:46372890:AGGGT:A	acceptor_gain	0.9800
3:46372891:GGGTG:G	acceptor_gain	0.9800
3:46372891:GGGT:G	acceptor_gain	0.9700
3:46372890:A:AG	acceptor_gain	0.9600
3:46372891:G:GG	acceptor_gain	0.9600
3:46372886:GCACA:G	acceptor_loss	0.9400
3:46372885:T:G	acceptor_gain	0.9100
3:46372888:A:AG	acceptor_gain	0.9100
3:46372888:ACAGG:A	acceptor_gain	0.9100
3:46372889:C:G	acceptor_gain	0.9100
3:46372884:A:AG	acceptor_gain	0.8900
3:46373039:T:TA	acceptor_gain	0.8600
3:46372885:T:TA	acceptor_gain	0.8300
3:46372890:AGG:A	acceptor_gain	0.7900
3:46372891:GGG:G	acceptor_gain	0.7900
3:46372884:AT:A	acceptor_gain	0.7500
3:46373040:G:A	acceptor_gain	0.7500

AlphaMissense

2321 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
3:46373347:A:C	S149R	0.996
3:46373349:T:A	S149R	0.996
3:46373349:T:G	S149R	0.996
3:46373359:T:A	W153R	0.994
3:46373359:T:C	W153R	0.994
3:46373184:G:C	W94C	0.993
3:46373184:G:T	W94C	0.993
3:46373812:T:C	F304L	0.987
3:46373814:C:A	F304L	0.987
3:46373814:C:G	F304L	0.987
3:46373115:C:A	N71K	0.986
3:46373115:C:G	N71K	0.986
3:46373203:T:A	C101S	0.986
3:46373204:G:C	C101S	0.986
3:46373434:T:A	C178S	0.986
3:46373435:G:C	C178S	0.986
3:46373734:G:C	A278P	0.985
3:46373182:T:A	W94R	0.984
3:46373182:T:C	W94R	0.984
3:46373773:T:C	C291R	0.983
3:46373117:T:C	L72P	0.981
3:46373519:C:G	P206R	0.981
3:46373033:G:A	G44D	0.980
3:46373046:C:A	N48K	0.980
3:46373046:C:G	N48K	0.980
3:46373129:A:C	D76A	0.980
3:46373435:G:A	C178Y	0.980
3:46373651:C:A	P250H	0.980
3:46373032:G:C	G44R	0.979
3:46373436:C:G	C178W	0.979

dbSNP variants (sampled 300 via entrez): RS1000094225 (3:46374473 C>A,T), RS1000252464 (3:46368837 C>G), RS1000526601 (3:46374682 G>C), RS1000545693 (3:46369984 G>A,T), RS1001504708 (3:46368455 C>T), RS1001552690 (3:46374066 G>A), RS1001641899 (3:46373873 G>A,C), RS1001800610 (3:46368683 C>G), RS1001866233 (3:46375136 C>T), RS1002017847 (3:46368147 G>A), RS1002031089 (3:46369221 T>C), RS1002062318 (3:46369488 C>A), RS1002336871 (3:46375422 TTA>T), RS1003011434 (3:46374945 G>T), RS1004022890 (3:46376340 A>G,T)

Disease associations

OMIM: gene MIM:601373 | disease phenotypes: MIM:609423, MIM:610379, MIM:609532, MIM:612522

GenCC curated gene-disease

Mondo (4): susceptibility to HIV infection (MONDO:0004951), West Nile virus, susceptibility to (MONDO:0012482), hepatitis C virus, susceptibility to (MONDO:0012292), type 1 diabetes mellitus 22 (MONDO:0012921)

Orphanet (0):

HPO phenotypes

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

GWAS associations

9 associations (top):

Study	Trait	p-value
GCST000612_32	Celiac disease	3.000000e-17
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_74	Granulocyte percentage of myeloid white cells	1.000000e-09
GCST005536_10	Type 1 diabetes	5.000000e-08
GCST009731_50	Blood protein levels in cardiovascular risk	8.000000e-83

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0006514	Alzheimer’s disease biomarker measurement
EFO:0007997	granulocyte percentage of myeloid white cells

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567284	Diabetes Mellitus, Insulin-Dependent, 22 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL274 (SINGLE PROTEIN), CHEMBL3301384 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 77,828 (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
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL2205807	ABAMETAPIR	4	748
CHEMBL256907	MARAVIROC	4	5
CHEMBL964	DISULFIRAM	4	38,611
CHEMBL1255794	APLAVIROC	3	916
CHEMBL1668019	APLAVIROC HYDROCHLORIDE	3	41
CHEMBL2110727	CENICRIVIROC	3	2,137
CHEMBL82301	VICRIVIROC	3	8,672
CHEMBL1688243	INCB-9471	2	149
CHEMBL1951914	AZD5672	2	219
CHEMBL397647	JNJ-17166864 CATION	2	36
CHEMBL4457723	BMS-741672	2	2
CHEMBL4594419	BMS-813160	2	57
CHEMBL78535	ANCRIVIROC	2	757
CHEMBL2105686	CENICRIVIROC MESYLATE	1	85

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs333	CCR5		0.00	0

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
CCL5	Full agonist	9.7	pKi
CCL4	Full agonist	9.6	pKi
[125I]CCL4 (human)	Full agonist	9.6	pKd
AZD5672	Antagonist	9.59	pIC50
CCL8	Full agonist	9.3	pKi
vicriviroc	Antagonist	9.1	pKi
CCL13	Full agonist	9.1	pKi
[3H]maraviroc	Antagonist	9.1	pKd
CCL3	Full agonist	8.9	pKi
[3H]ancriviroc	Antagonist	8.9	pKd
E913	Antagonist	8.7	pIC50
ancriviroc	Antagonist	8.7	pKi
BMS-681	Antagonist	8.62	pIC50
cenicriviroc	Antagonist	8.6	pIC50
CCR5 antagonist 34	Antagonist	8.52	pIC50
TAK-220	Antagonist	8.5	pIC50
aplaviroc	Antagonist	8.5	pKi
vMIP-II	Antagonist	8.3	pIC50
maraviroc	Antagonist	8.1	pIC50
BP-CCL3	Full agonist	7.7	pKi
CCL11	Full agonist	7.7	pIC50
Flu-CCL3	Full agonist	7.6	pKi
CCL7	Antagonist	7.5	pKi
CCL2	Full agonist	7.5	pKi
TAK-779	Antagonist	7.5	pKi

Binding affinities (BindingDB)

224 measured of 225 human assays (225 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
endo-methyl 3-(8-((S)-3-acetamido-3-(3-fluorophenyl)propyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-methyl-6,7-dihydro-3H-imidazo[4,5-c]pyridine-5(4H)-carboxylate	IC50	0.1 nM
endo-methyl(S)-3-(3-(5-acetyl-2-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-(3-fluorophenyl)propylcarbamate	IC50	0.2 nM
endo-methyl 3-(8-((S)-3-(3-fluorophenyl)-3-(methoxycarbonylamino)propyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-methyl-6,7-dihydro-3H-imidazo[4,5-c]pyridine-5(4H)-carboxylate	IC50	0.2 nM
4,4-difluoro-N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide	KI	0.24 nM	US-9107954: Bivalent ligands for the treatment of neurological disorders
endo-methyl 3-(8-((S)-3-acetamido-3-phenylpropyl)-8-azabicyclo[3.2.1]octan-3-yl)-2-methyl-6,7-dihydro-3H-imidazo[4,5-c]pyridine-5(4H)-carboxylate	IC50	0.3 nM
CHEMBL1784385	IC50	0.355 nM
endo-N-((S)-3-(3-(5-isobutyryl-2-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)acetamide	IC50	0.4 nM
endo-N-((S)-3-(3-(2-methyl-5-propionyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)acetamide	IC50	0.4 nM
endo-N-((S)-3-(3-(5-acetyl-2-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)acetamide	IC50	0.4 nM
CHEMBL257000	IC50	0.4 nM
endo-methyl(S)-3-(3-(5-acetyl-2-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropylcarbamate	IC50	0.6 nM
methyl 2-(4-fluorophenyl)-2-(4-(2-(3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)ethyl)-4-phenylpiperidin-1-yl)acetate	IC50	0.9 nM
CHEMBL3109175	IC50	0.96 nM
exo-N-benzyl-N-((R)-1-(8-(2,6-dimethylbenzoyl)-8-azabicyclo[3.2.1]octan-3-yl)pyrrolidin-3-yl)cyclopropanecarboxamide	IC50	1 nM
CHEMBL454251	IC50	1 nM
4,4-difluoro-N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-3-ylpropyl]cyclohexane-1-carboxamide	IC50	1.05 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-1-(5-fluorothiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]-2-(tetrazol-2-yl)acetamide	IC50	1.23 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-1-[5-(hydroxymethyl)thiophen-2-yl]-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]-2-(2H-tetrazol-5-yl)acetamide	IC50	1.34 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
[5-[(1S)-1-(cyclohexanecarbonylamino)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]thiophen-2-yl] acetate	IC50	1.38 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-1-(5-fluorothiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]cyclopentanecarboxamide	IC50	1.41 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-1-(5-chlorothiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]-2-cyanoacetamide	IC50	1.54 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
CHEMBL2163486	KD	1.6 nM
N-[(1S)-1-(5-ethylthiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]cyclohexanecarboxamide	IC50	1.62 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
5-[(1S)-1-(cyclohexanecarbonylamino)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]-N,N-dimethylthiophene-2-carboxamide	IC50	1.64 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]-1-methylsulfonylpiperidine-4-carboxamide	IC50	1.75 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
methyl 1-[8-[(3S)-3-acetamido-3-(5-fluorothiophen-2-yl)propyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridine-5-carboxylate	IC50	1.79 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-1-(5-chlorothiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]-2-(2H-tetrazol-5-yl)acetamide	IC50	1.85 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
Compound 3	IC50	1.95 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
(E)-methyl N-cyano-4-(2-(3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)ethyl)-4-phenylpiperidine-1-carbimidate	IC50	2 nM
endo-N-((S)-3-(3-(2-methyl-5-(methylsulfonyl)-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)acetamide	IC50	2 nM
CHEMBL2203615	IC50	2 nM
N-[(1S)-1-(5-ethylthiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]cyclopentanecarboxamide	IC50	2.02 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-1-(5-chlorothiophen-2-yl)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]-1-methylsulfonylpiperidine-4-carboxamide	IC50	2.22 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexanecarboxamide	IC50	2.23 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
CHEMBL4248009	IC50	2.3 nM
4,4-difluoro-N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-thiophen-2-ylpropyl]cyclohexane-1-carboxamide	IC50	2.33 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-3-[3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-(5-methylthiophen-2-yl)propyl]-1-methylsulfonylpiperidine-4-carboxamide	IC50	2.48 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-thiophen-2-ylpropyl]cyclopentanecarboxamide	IC50	2.55 nM	US-10167299: 1-(3-aminopropyl) substituted cyclic amine compounds, preparation method therefor, and pharmaceutical compositions and uses thereof
CHEMBL4242489	IC50	2.6 nM
CHEMBL4242913	IC50	2.6 nM
CHEMBL4248472	IC50	2.6 nM
CHEMBL4248282	IC50	2.8 nM
CHEMBL4240475	IC50	2.8 nM
CHEMBL4241721	IC50	2.9 nM
CHEMBL4239790	IC50	2.9 nM
CHEMBL4244672	IC50	2.9 nM
(E)-isopropyl N-cyano-4-(2-(3-(2-methyl-1H-benzo[d]imidazol-1-yl)-8-azabicyclo[3.2.1]octan-8-yl)ethyl)-4-phenylpiperidine-1-carbimidate	IC50	3 nM
endo-N-((S)-3-(3-(5-isopropyl-2-methyl-4,5,6,7-tetrahydro-3H-imidazo[4,5-c]pyridin-3-yl)-8-azabicyclo[3.2.1]octan-8-yl)-1-phenylpropyl)acetamide	IC50	3 nM
CHEMBL3109172	IC50	3 nM
CHEMBL4237964	IC50	3 nM

ChEMBL bioactivities

3034 potent at pChembl≥5 of 3211 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
11.00	IC50	0.01	nM	CHEMBL311795
10.30	IC50	0.05	nM	CHEMBL460845
10.22	IC50	0.06	nM	CHEMBL21106
10.22	IC50	0.06	nM	CHEMBL181276
10.22	IC50	0.05998	nM	CHEMBL21106
10.15	IC50	0.07	nM	CHEMBL457043
10.10	IC50	0.08	nM	CHEMBL2164207
10.05	IC50	0.09	nM	CHEMBL1926899
10.00	IC50	0.1	nM	CHEMBL20345
10.00	IC50	0.1	nM	CHEMBL20896
10.00	IC50	0.1	nM	CHEMBL2164210
10.00	IC50	0.1	nM	CHEMBL2164202
10.00	IC50	0.1	nM	CENICRIVIROC MESYLATE
10.00	IC50	0.1	nM	CHEMBL328445
10.00	IC50	0.1	nM	CHEMBL316475
10.00	IC50	0.1	nM	CHEMBL320386
10.00	IC50	0.1	nM	CHEMBL93139
10.00	IC50	0.1	nM	CHEMBL1649924
10.00	Ki	0.1	nM	CHEMBL140484
10.00	IC50	0.1	nM	CHEMBL102826
9.96	IC50	0.11	nM	CHEMBL2164217
9.89	IC50	0.13	nM	CHEMBL157491
9.86	IC50	0.137	nM	CHEMBL473558
9.80	IC50	0.16	nM	CHEMBL461687
9.77	IC50	0.17	nM	AZD-5363
9.74	EC50	0.18	nM	CHEMBL2372983
9.72	IC50	0.19	nM	CHEMBL3085308
9.70	IC50	0.2	nM	CHEMBL171958
9.70	IC50	0.2	nM	CHEMBL369235
9.70	IC50	0.2	nM	CHEMBL21147
9.70	IC50	0.2	nM	CHEMBL366770
9.70	IC50	0.2	nM	CHEMBL173400
9.70	IC50	0.2	nM	CHEMBL20622
9.70	IC50	0.2	nM	CHEMBL174927
9.70	IC50	0.2	nM	CENICRIVIROC MESYLATE
9.70	IC50	0.2	nM	MARAVIROC
9.70	IC50	0.2	nM	CHEMBL319593
9.70	IC50	0.2	nM	CHEMBL99909
9.70	IC50	0.2	nM	CHEMBL329893
9.70	IC50	0.2	nM	CHEMBL431852
9.70	IC50	0.2	nM	CHEMBL1649926
9.70	IC50	0.2	nM	CHEMBL1649927
9.70	IC50	0.2	nM	CHEMBL102826
9.70	IC50	0.2	nM	CHEMBL1926893
9.70	IC50	0.2	nM	CHEMBL322422
9.68	IC50	0.21	nM	CHEMBL3085309
9.66	IC50	0.22	nM	CHEMBL212731
9.64	IC50	0.2301	nM	CHEMBL520091
9.64	IC50	0.2301	nM	CHEMBL511493
9.64	IC50	0.23	nM	CHEMBL520091

PubChem BioAssay actives

2733 with measured affinity, of 3712 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
N-[(1S)-3-[4-[(3,4-dichlorophenyl)methylcarbamoyl-ethylamino]piperidin-1-yl]-1-phenylbutyl]cyclobutanecarboxamide	393050: Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay	ic50	<0.0001	uM
(4,6-dimethylpyrimidin-5-yl)-[4-methyl-4-[(3S)-3-methyl-4-[(1S)-1-[4-(trifluoromethyl)phenyl]ethyl]piperazin-1-yl]piperidin-1-yl]methanone	42493: Inhibition of 0.1 nM of MIP-1beta induced migration of recombinant mouse pro-B cell line BA/F3 expressing human CCR5	ic50	<0.0001	uM
(2R)-3-cyclopropyl-2-[(3S,4S)-3-[[4-[3,3-difluoro-3-(4-fluorophenyl)propyl]piperidin-1-yl]methyl]-4-(3-fluorophenyl)pyrrolidin-1-yl]propanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0001	uM
(5E)-8-[4-(2-butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-[4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide;methanesulfonic acid	261802: Inhibition of membrane fusion between HIV1 JR-FL Env-expressing COS7 cells and MOLT4/CCR5	ic50	0.0001	uM
N-[(1S)-1-(3-fluorophenyl)-3-[(1R,5S)-3-(2-methyl-5-propanoyl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-3-[4-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)piperidin-1-yl]-1-phenylbutyl]cyclopentanecarboxamide	395483: Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay	ic50	0.0001	uM
6-chloro-2,4-dimethyl-N-[(3R)-3-[4-[[2-(2-oxo-1,3-oxazolidin-3-yl)acetyl]-(thiophen-3-ylmethyl)amino]piperidin-1-yl]butyl]pyridine-3-carboxamide	696934: Antagonist activity at CCR5 receptor expressed in P4R5 cells co-expressing CD4, and LTR-beta-gal construct assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat cells expressing HIV-1 JRFLenv and HIV-1 Tat by beta-galactosidase activity based cell-cell fusion assay	ic50	0.0001	uM
2-chloro-6-cyano-N-[(3R)-3-[4-[methoxycarbamoyl(thiophen-3-ylmethyl)amino]piperidin-1-yl]butyl]-4-methylpyridine-3-carboxamide	696934: Antagonist activity at CCR5 receptor expressed in P4R5 cells co-expressing CD4, and LTR-beta-gal construct assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat cells expressing HIV-1 JRFLenv and HIV-1 Tat by beta-galactosidase activity based cell-cell fusion assay	ic50	0.0001	uM
2,6-dichloro-N-[(3R)-3-[4-[methoxycarbamoyl(thiophen-3-ylmethyl)amino]piperidin-1-yl]butyl]-4-methylpyridine-3-carboxamide	696934: Antagonist activity at CCR5 receptor expressed in P4R5 cells co-expressing CD4, and LTR-beta-gal construct assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat cells expressing HIV-1 JRFLenv and HIV-1 Tat by beta-galactosidase activity based cell-cell fusion assay	ic50	0.0001	uM
(2S)-N-[(2S)-1-[[(2S,3R)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S,3R)-2-[[(2S)-2-[[(2R)-2-aminopropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]-3-hydroxybutanoyl]amino]butanediamide	1928524: Antagonist activity at CCR5 (unknown origin) expressed in human HOS cells co-expressing HIV-1 FITC-gp120 Bal assessed inhibition of CD4 dependent gp120 Bal binding to CCR5 by western blot analysis	ic50	0.0001	uM
(4-nitrophenyl)methyl N-[1-[(3S)-4-[benzenesulfonyl(methyl)amino]-3-methyl-3-phenylbutyl]piperidin-4-yl]-N-prop-2-enylcarbamate	42496: Inhibitory concentration, binding towards C-C chemokine receptor type 5 using [125I]-MIP-1 alpha as radioligand expressed on CHO cells	ic50	0.0001	uM
(2R)-3-cyclobutyl-2-[(3S,4S)-3-(3-fluorophenyl)-4-[[4-[2-(4-fluorophenyl)sulfanylethyl]piperidin-1-yl]methyl]pyrrolidin-1-yl]propanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0001	uM
(2R)-3-cyclopropyl-2-[(3S,4S)-3-phenyl-4-[[4-(3-phenylpropyl)piperidin-1-yl]methyl]pyrrolidin-1-yl]propanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0001	uM
(4-nitrophenyl)methyl N-[1-[[(3aS,4S,5S)-4-phenylspiro[3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-b][1,2]oxazole-2,1’-cyclohexane]-5-yl]methyl]piperidin-4-yl]-N-prop-2-enylcarbamate	42378: Ability to displace [125I]-labeled MIP-1alpha from the C-C chemokine receptor type 5 expressed on CHO cell membranes	ic50	0.0001	uM
N-[(1S)-3-[4-[[2-(3,4-dichlorophenyl)acetyl]-ethylamino]piperidin-1-yl]-1-phenylbutyl]cyclobutanecarboxamide	393050: Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-3-[4-[ethyl-[2-(4-methylsulfonylphenyl)acetyl]amino]piperidin-1-yl]-1-phenylbutyl]cyclobutanecarboxamide	393050: Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay	ic50	0.0001	uM
(4-nitrophenyl)methyl N-[1-[[(3S,4S)-1-benzyl-4-phenylpyrrolidin-3-yl]methyl]piperidin-4-yl]-N-prop-2-enylcarbamate	1957048: Inhibition of human CCR5	ic50	0.0001	uM
(2R)-2-cyclohexyl-2-[(3S,4S)-3-phenyl-4-[[4-(3-phenylpropyl)piperidin-1-yl]methyl]pyrrolidin-1-yl]acetic acid	42379: In vitro binding affinity at CCR5 receptor in the presence of [125I]-MIP-1 alpha.	ic50	0.0001	uM
(2R)-2-cyclobutyl-2-[(3S,4S)-3-phenyl-4-[[4-(3-phenylpropyl)piperidin-1-yl]methyl]pyrrolidin-1-yl]acetic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0001	uM
(2R)-3-cyclobutyl-2-[(3S,4S)-3-phenyl-4-[[4-(3-phenylpropyl)piperidin-1-yl]methyl]pyrrolidin-1-yl]propanoic acid	241856: Displacement of [125I]-MIP-1 alpha from human C-C chemokine receptor type 5 expressed on CHO cell membranes	ic50	0.0001	uM
methyl 1-[(1R,5S)-8-[(3S)-3-acetamido-3-(3-fluorophenyl)propyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridine-5-carboxylate	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
propan-2-yl 3-[(1S,5R)-8-[(3S)-3-acetamido-3-phenylpropyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridine-5-carboxylate	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-1-(3-fluorophenyl)-3-[(1R,5S)-3-(2-methyl-5-pyrimidin-4-yl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-1-(3-fluorophenyl)-3-[(1R,5S)-3-(2-methyl-5-pyrazin-2-yl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-3-[(1R,5S)-3-(5-acetyl-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-(3-fluorophenyl)propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-3-[(1R,5S)-3-(5-butanoyl-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-(3-fluorophenyl)propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-3-[(1R,5S)-3-[5-(2,2-dimethylpropanoyl)-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl]-8-azabicyclo[3.2.1]octan-8-yl]-1-(3-fluorophenyl)propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
methyl 3-[(1S,5R)-8-[(3S)-3-acetamido-3-(3-fluorophenyl)propyl]-8-azabicyclo[3.2.1]octan-3-yl]-2-methyl-6,7-dihydro-4H-imidazo[4,5-c]pyridine-5-carboxylate	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[(1S)-1-(3-fluorophenyl)-3-[(1R,5S)-3-[2-methyl-5-(2-methylpropanoyl)-6,7-dihydro-4H-imidazo[4,5-c]pyridin-1-yl]-8-azabicyclo[3.2.1]octan-8-yl]propyl]acetamide	554132: Antagonist activity at CCR5 receptor expressed in HeLa-P4 cells co-expressing CD4 assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat10 cells after 20 hrs by cell-cell fusion assay	ic50	0.0001	uM
N-[1-[(3R)-3-(3,5-dichlorophenyl)-3-(1-methylsulfonylpiperidin-4-yl)propyl]piperidin-4-yl]-N-ethyl-2-(4-methylsulfonylphenyl)acetamide	645643: Displacement of [125I]MIP-1alpha from human recombinant CCR5 expressed in CHO cells	ic50	0.0001	uM
N-ethyl-2-(4-methylsulfonylphenyl)-N-[1-[(3R)-3-phenyl-3-[1-(trifluoromethylsulfonyl)piperidin-4-yl]propyl]piperidin-4-yl]acetamide	645643: Displacement of [125I]MIP-1alpha from human recombinant CCR5 expressed in CHO cells	ic50	0.0001	uM
N-[1-[(3R)-3-(3,5-dimethylphenyl)-3-(1-methylsulfonylpiperidin-4-yl)propyl]piperidin-4-yl]-N-ethyl-2-(4-methylsulfonylphenyl)acetamide	645643: Displacement of [125I]MIP-1alpha from human recombinant CCR5 expressed in CHO cells	ic50	0.0001	uM
5-N-[(3R)-3-[4-[4-methoxy-N-[(4-methyl-3-pyridinyl)methyl]anilino]piperidin-1-yl]butyl]-4,6-dimethyl-2-N-propan-2-ylpyridine-2,5-dicarboxamide	635152: Antagonist activity against human CCR5 assessed as inhibition of HIV1 gp120-induced cell-cell fusion between human HeLa P4/R5 cells and CHO-tat10 cells expressing HIV-1JRFL viral envolop protein after 20 hrs by beta-galactosidase reporter gene assay	ic50	0.0001	uM
6-chloro-2,4-dimethyl-N-[(3R)-3-[4-[pyridin-3-ylcarbamoyl(thiophen-3-ylmethyl)amino]piperidin-1-yl]butyl]pyridine-3-carboxamide	696934: Antagonist activity at CCR5 receptor expressed in P4R5 cells co-expressing CD4, and LTR-beta-gal construct assessed as inhibition of infusion to HIV gp120 expressed in CHO-tat cells expressing HIV-1 JRFLenv and HIV-1 Tat by beta-galactosidase activity based cell-cell fusion assay	ic50	0.0001	uM
[4-[4-[(E)-C-(4-bromophenyl)-N-ethoxycarbonimidoyl]piperidin-1-yl]-4-methylpiperidin-1-yl]-(2,6-dimethyl-4-pyridin-4-ylphenyl)methanone	42506: Inhibition of RANTES binding to the human C-C chemokine receptor type 5 (CCR5)	ki	0.0001	uM
1-[[(3S,4S)-1-(cyclohexylmethyl)-4-phenylpyrrolidin-3-yl]methyl]-4-[3-[4-(2H-tetrazol-5-yl)phenyl]propyl]piperidin-4-ol	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0002	uM
(5E)-8-[4-(2-butoxyethoxy)phenyl]-1-[(1-methylpyrazol-4-yl)methyl]-N-[4-[(S)-(3-propylimidazol-4-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide	261802: Inhibition of membrane fusion between HIV1 JR-FL Env-expressing COS7 cells and MOLT4/CCR5	ic50	0.0002	uM
(5E)-8-[4-(2-butoxyethoxy)phenyl]-1-(2-methylpropyl)-N-[4-[(S)-(4-propyl-1,2,4-triazol-3-yl)methylsulfinyl]phenyl]-3,4-dihydro-2H-1-benzazocine-5-carboxamide	261802: Inhibition of membrane fusion between HIV1 JR-FL Env-expressing COS7 cells and MOLT4/CCR5	ic50	0.0002	uM
6-chloro-N-[(3R)-3-[4-[4-methoxy-N-[(4-methyl-3-pyridinyl)methyl]anilino]piperidin-1-yl]butyl]-2,4-dimethylpyridine-3-carboxamide	635152: Antagonist activity against human CCR5 assessed as inhibition of HIV1 gp120-induced cell-cell fusion between human HeLa P4/R5 cells and CHO-tat10 cells expressing HIV-1JRFL viral envolop protein after 20 hrs by beta-galactosidase reporter gene assay	ic50	0.0002	uM
4,4-difluoro-N-[(1S)-3-[(1S,5R)-3-(3-methyl-5-propan-2-yl-1,2,4-triazol-4-yl)-8-azabicyclo[3.2.1]octan-8-yl]-1-phenylpropyl]cyclohexane-1-carboxamide	1370975: Inhibition of CCR5 in human TZM-bl cells infected with HIV1 Bal R5 assessed as antiviral activity by measuring reduction in viral infection pre-incubated with cells followed by viral infection measured after 3 days by luciferase reporter gene assay	ic50	0.0002	uM
(2R)-2-[(3S,4S)-3-[[4-(2-benzyl-1,3-thiazol-5-yl)piperidin-1-yl]methyl]-4-phenylpyrrolidin-1-yl]-3-cyclopropylpropanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0002	uM
(2R)-2-[(3S,4S)-3-[[4-(2-benzyl-1,3-thiazol-5-yl)piperidin-1-yl]methyl]-4-phenylpyrrolidin-1-yl]-3-cyclobutylpropanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0002	uM
(2R)-3-cyclobutyl-2-[(3S,4S)-3-(3-fluorophenyl)-4-[[4-[3-[4-(trifluoromethyl)phenyl]propyl]piperidin-1-yl]methyl]pyrrolidin-1-yl]propanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0002	uM
(2R)-3-cyclobutyl-2-[(3S,4S)-3-[[4-[3,3-difluoro-3-(4-fluorophenyl)propyl]piperidin-1-yl]methyl]-4-phenylpyrrolidin-1-yl]propanoic acid	352100: Displacement of [125I]MIP1alpha from human CCR5 expressed in CHO cells	ic50	0.0002	uM
1-[[(3S,4S)-1-(cyclohexylmethyl)-4-phenylpyrrolidin-3-yl]methyl]-4-[3-[4-(1-methyltetrazol-5-yl)phenyl]propyl]piperidin-4-ol	42380: Displacement of [125I]-labeled MIP-1alpha from the C-C chemokine receptor type 5 expressed on CHO cell membranes	ic50	0.0002	uM
2-[(3S)-3-[[4-(2-benzyl-1,3-thiazol-5-yl)piperidin-1-yl]methyl]-4-phenylpyrrolidin-1-yl]-3-cyclobutylpropanoic acid	42495: Inhibition of human C-C chemokine receptor type 5 assayed using [125I]-MIP-1 alpha as radioligand	ic50	0.0002	uM
2-[(3S)-3-[[4-(2-benzyl-1,3-thiazol-5-yl)piperidin-1-yl]methyl]-4-phenylpyrrolidin-1-yl]-3-cyclopropylpropanoic acid	42495: Inhibition of human C-C chemokine receptor type 5 assayed using [125I]-MIP-1 alpha as radioligand	ic50	0.0002	uM
N-[(1S)-3-[4-[benzylcarbamoyl(ethyl)amino]piperidin-1-yl]-1-phenylbutyl]cyclobutanecarboxamide	393050: Antagonist activity at human recombinant CCR5 expressed in human HeLa-P4 cells assessed as inhibition of human HeLa-P4 cells binding to HIV1 gp160 expressing CHO cells by cell-cell fusion assay	ic50	0.0002	uM
(4-nitrophenyl)methyl N-[1-[[(3S,4S)-1-benzoyl-4-phenylpyrrolidin-3-yl]methyl]piperidin-4-yl]-N-prop-2-enylcarbamate	42496: Inhibitory concentration, binding towards C-C chemokine receptor type 5 using [125I]-MIP-1 alpha as radioligand expressed on CHO cells	ic50	0.0002	uM
(4-nitrophenyl)methyl N-[1-[[(3S,4S)-1-(cyclopentanecarbonyl)-4-phenylpyrrolidin-3-yl]methyl]piperidin-4-yl]-N-prop-2-enylcarbamate	42496: Inhibitory concentration, binding towards C-C chemokine receptor type 5 using [125I]-MIP-1 alpha as radioligand expressed on CHO cells	ic50	0.0002	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Maraviroc	affects binding, decreases activity, decreases reaction	2
Benzo(a)pyrene	affects methylation, increases expression	2
Eugenol	increases expression	2
Nickel	affects expression, increases expression, decreases reaction	2
Simvastatin	decreases expression, decreases reaction, increases expression	2
GSK-J4	decreases expression	1
isopentenyl pyrophosphate	decreases expression	1
triphenyl phosphate	affects expression	1
captax	increases expression	1
trichostatin A	affects expression, decreases reaction	1
proanthocyanidin	decreases expression	1
indole-3-carbinol	increases expression	1
3-chlorophenol	decreases expression	1
2,4-dinitrofluorobenzene sulfonic acid	increases expression	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one	increases expression, affects binding, decreases reaction, increases activity	1
enniatins	decreases expression	1
cirsimarin	decreases expression	1
TAK 779	affects binding, decreases reaction	1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride	affects cotreatment, decreases expression, decreases reaction	1
Ancriviroc	affects binding, decreases reaction	1
bardoxolone methyl	increases expression, increases reaction	1
vicriviroc	affects binding, decreases reaction	1
aplaviroc	affects binding, decreases reaction	1
PF 232798	affects binding, decreases activity	1
bisphenol S	decreases methylation	1
gardiquimod	increases expression, decreases reaction	1
(+)-JQ1 compound	decreases expression	1
Vehicle Emissions	increases expression	1

ChEMBL screening assays

409 unique, capped per target: 243 binding, 166 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1000791	Binding	Displacement of [125I]gp-120 from human CCR5 receptor expressed in CHO cells	Isolation and structure of antagonists of chemokine receptor (CCR5). — J Nat Prod
CHEMBL1055686	Functional	Inhibition of human CCR5 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

60 cell lines: 45 cancer cell line, 6 spontaneously immortalized cell line, 5 induced pluripotent stem cell, 4 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0C87	MOCHA	Cancer cell line	Male
CVCL_1D98	HOS-CD4-CCR5	Cancer cell line	Female
CVCL_1E08	GHOST(3).R3/X4/R5	Cancer cell line	Female
CVCL_1E10	GHOST(3).X4/R5	Cancer cell line	Female
CVCL_1E15	3T3.T4.CCR5	Transformed cell line	Male
CVCL_1E17	GHOST(3).Hi-5	Cancer cell line	Female
CVCL_1F85	U373-MAGI-CCR5	Cancer cell line	Male
CVCL_1G50	Cf2Th-CCR5	Spontaneously immortalized cell line	Female
CVCL_1H19	HOS-CCR5	Cancer cell line	Female
CVCL_1H21	HeLa-P4-R5 MAGI	Cancer cell line	Female

Clinical trials (associated diseases)

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