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CCR4

gene
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Also known as CC-CKR-4CMKBR4CKR4k5-5ChemR13CD194

Summary

CCR4 (C-C motif chemokine receptor 4, HGNC:1605) is a protein-coding gene on chromosome 3p22.3, encoding C-C chemokine receptor type 4 (P51679). High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1.

The protein encoded by this gene belongs to the G-protein-coupled receptor family . It is a receptor for the CC chemokine - MIP-1, RANTES, TARC and MCP-1. Chemokines are a group of small polypeptide, structurally related molecules that regulate cell trafficking of various types of leukocytes. The chemokines also play fundamental roles in the development, homeostasis, and function of the immune system, and they have effects on cells of the central nervous system as well as on endothelial cells involved in angiogenesis or angiostasis.

Source: NCBI Gene 1233 — RefSeq curated summary.

At a glance

  • Clinical variants (ClinVar): 39 total — 1 pathogenic
  • Druggable target: yes — 7 molecules with ChEMBL bioactivity
  • MANE Select transcript: NM_005508

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:1605
Approved symbolCCR4
NameC-C motif chemokine receptor 4
Location3p22.3
Locus typegene with protein product
StatusApproved
AliasesCC-CKR-4, CMKBR4, CKR4, k5-5, ChemR13, CD194
Ensembl geneENSG00000183813
Ensembl biotypeprotein_coding
OMIM604836
Entrez1233

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000330953, ENST00000718415

RefSeq mRNA: 1 — MANE Select: NM_005508 NM_005508

CCDS: CCDS2656

Canonical transcript exons

ENST00000330953 — 2 exons

ExonStartEnd
ENSE000013180003295337232956349
ENSE000013825753295164432951690

Expression profiles

Bgee: expression breadth ubiquitous, 109 present calls, max score 76.13.

FANTOM5 (CAGE): breadth broad, TPM avg 17.3134 / max 1226.7401, expressed in 318 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter IDTPM avgSamples expressed
3592811.9678266
359274.0890147
359250.762089
359260.170761
359230.120455
359290.109749
359240.093752

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047376.13gold quality
vermiform appendixUBERON:000115473.05gold quality
lymph nodeUBERON:000002972.66gold quality
granulocyteCL:000009471.75gold quality
gall bladderUBERON:000211070.30gold quality
leukocyteCL:000073868.09gold quality
caecumUBERON:000115367.76gold quality
monocyteCL:000057666.50gold quality
bloodUBERON:000017864.49gold quality
colonic epitheliumUBERON:000039763.80silver quality
bone marrow cellCL:000209261.83silver quality
rectumUBERON:000105261.13gold quality
spleenUBERON:000210661.01gold quality
right lungUBERON:000216760.99gold quality
upper lobe of left lungUBERON:000895258.04gold quality
tonsilUBERON:000237257.09gold quality
upper lobe of lungUBERON:000894856.52gold quality
smooth muscle tissueUBERON:000113555.78gold quality
parotid glandUBERON:000183154.08gold quality
lungUBERON:000204853.30gold quality
small intestine Peyer’s patchUBERON:000345451.81gold quality
small intestineUBERON:000210850.79gold quality
bone marrowUBERON:000237150.78gold quality
mucosa of transverse colonUBERON:000499150.65gold quality
frontal poleUBERON:000279550.41gold quality
middle frontal gyrusUBERON:000270250.30gold quality
paraflocculusUBERON:000535150.18gold quality
Brodmann (1909) area 10UBERON:001354150.18gold quality
blood vessel layerUBERON:000479749.29gold quality
cerebellar vermisUBERON:000472049.25gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-CURD-97no424.05
E-ANND-3no3.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, FOSL2, FOXP3, JUNB, JUND, MAF, MYC, NCOR1, NCOR2, NOTO, STAT6, TBX21, ZBTB17

miRNA regulators (miRDB)

23 targeting CCR4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNAMax scoreAvg scoremiRNA target_count
HSA-MIR-3064-3P100.0070.091254
HSA-MIR-6748-5P100.0065.811057
HSA-MIR-453199.9969.703181
HSA-MIR-4666A-3P99.9671.713434
HSA-MIR-430699.7270.503630
HSA-MIR-10394-5P99.6566.831852
HSA-MIR-120599.6566.761826
HSA-MIR-642A-5P99.5165.101152
HSA-MIR-751599.3168.221795
HSA-MIR-6731-5P99.2867.422375
HSA-MIR-808599.2867.562362
HSA-MIR-146A-3P99.1368.991881
HSA-MIR-315498.9466.551455
HSA-MIR-5006-5P98.7966.921246
HSA-MIR-6796-3P98.6865.49689
HSA-MIR-6509-3P98.3267.331343
HSA-MIR-1233-5P98.1966.711201
HSA-MIR-6778-5P98.1966.591239
HSA-MIR-6841-3P98.0866.54604
HSA-MIR-449497.8664.93850
HSA-MIR-449196.5366.20935
HSA-MIR-465796.5366.57895
HSA-MIR-7160-3P96.4064.15462

Literature-anchored findings (GeneRIF, showing 40)

  • CCR4 is expressed with high frequency in adult T-cell leukemia and human T-cell leukemia virus type 1-transformed T cells and in ATL skin lesions. (PMID:11861261)
  • CCR4 is mainly expressed by a high cytokine (interleukin-4/interleukin-2)-producing (CD4) subset of natural killer t-cells. (PMID:12070001)
  • Selective CCL5/RANTES-induced mast cell migration through interactions with chemokine receptors (PMID:12270118)
  • The skin-homing TH compartment is itself divided into distinct subpopulations, the smaller of which expresses both CCR4 and CCR10, and the larger of which expresses only CCR4. (PMID:12406880)
  • CCR4+ cells were present predominantly in the lesional skin of atopic dermatitis patients, but not in the non-lesional skin (PMID:12456591)
  • In the blood of cutaneous T cell lymphoma patients with peripheral blood involvement we found significantly increased percentages of T cells displaying the skin-homing phenotype (CLA+CCR4+) compared with healthy individuals. (PMID:12485447)
  • Increased expression of CCR4, which is proposed to guide CD25(+) Ts cells to DC, is an intrinsic feature of CD25(+) Ts cells. (PMID:12778466)
  • airway allergen-specific T(H)2 cells are CCR4(+), but in the atopic child CCR4 does not distinguish between recall antigen and allergen specificity (PMID:14657875)
  • although there is PI(3,4,5)P(3) accumulation downstream of CCR4, phosphoinositide 3-kinase activity is a dispensable signal for CCR4-stimulated chemotaxis of Th2 cells and the CEM T cell line. (PMID:15187160)
  • CXCR3 and CCR4 were heterogeneously expressed in peripheral T-cell lymphomas. (PMID:15328188)
  • CC chemokine receptor 4 has a role in adult T-Cell leukemia/lymphoma (PMID:15569983)
  • review of possible relationship of CCR4 role in T cell migration and skin infiltration in ATL, and of selective expression of CCR4 by Th2 and regulatory T cells and possible origin of ATL in Th2 or regulatory T cells. (PMID:15621800)
  • CCR4 and TARC/CCL17 play role in pathophysiology of cutaneous lupus erythematosus(CLE). Cytotoxic CD8+ T cells expressing CCR4 appear to be involved in scarring subtypes of CLE. (PMID:15955100)
  • CCR4 and CCR10 may play an important role in ATLL invasion into the skin (PMID:17071491)
  • Bexarotene reduces CCR4-positive lymphocytes. (PMID:17546636)
  • aberrantly expressed Fra-2 in association with JunD may play a major role in CCR4 expression and oncogenesis in adult T-cell leukemia. (PMID:18071306)
  • CCR4 and CCR10 are expressed on epidermal keratinocytes and that both are functional in terms of skin cytokine production and/or migration to their ligand CCL17 and CCL27, respectively. (PMID:18782672)
  • ratio of CCR4+/CXCR3+ cells was 4.45 in chemotherapy and 0.72 in immunotherapy (PMID:19106589)
  • provide further dynamic evidence, in line with the multistep cascade paradigm for leukocyte transendothelial migration, to support a critical role for CCR4 in cutaneous T-cell lymphoma migration (PMID:19239991)
  • Regulatory T cells recruited through CCL22/CCR4 are selectively activated in lymphoid infiltrates surrounding primary breast tumors and lead to an adverse clinical outcome. (PMID:19244125)
  • CCR4 was expressed on a part of the memory cell population and CCR4+CD8+ memory T cells had the ability to produce multiple cytokines including IL-4 and to migrate in response to CC chemokine receptor ligand (CCL)17/TARC and CCL22/MDC. (PMID:19261691)
  • CCR4, a chemokine receptor known to be selectively expressed by T cell subsets such as Th2 cells, skin-homing memory/effector T cells, and regulatory T cells. (review) (PMID:19374191)
  • Data show that TH treatment promoted rapid and sustained hCCR4 recruitment to the TH-responsive deiodinase 1 promoter and TR co-localizes with hCCR4 in the nucleus and interacts with hCCR4 in 2-hybrid and pull-down assays. (PMID:19903885)
  • Data show that MDC/CCL22 is present in the synovial membrane of rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients and in synovial fluid of patients with RA and PsA, which would enable migration of CCR4 expressing memory cells. (PMID:19942450)
  • Lymphocyte CCR4 expression is closely associated with induction of human allergen-induced late nasal responses. (PMID:20148806)
  • CCR4 ligands secreted by dendritic cells recruit regulatory T cells (Tregs) to sites of inflammation in patients with autoimmune and chronic hepatitis. (PMID:20164417)
  • CCR4 might play a role in allergen-driven T helper type (Th)2 cell accumulation in asthmatic airways. (PMID:20237293)
  • We suggest that CCR4 and CCR6 expression on CD4(+) T cells should be considered as markers of disease activity in systemic lupus erythematosus. (PMID:20334681)
  • data support the role of DCs in differential regulation of CCR3 and CCR4 on CD4+ T cells from HDM-sensitive and non-atopic asthmatics after Der p 1 exposure. (PMID:20364559)
  • CD4+CD25high Treg cells of Wegener granulomatosis-patients exhibited decreased numbers of cells co-expressing FoxP3 and CCR4 (PMID:20412707)
  • high-level lineage-independent induction of CCR4 can occur following T-cell activation without accessibility-associated changes in histone H3, but that without such changes expression is transient rather than persistent. (PMID:20963786)
  • aberrant expression of CCR4 in human gastric cancer could contribute to tumor-induced immunosuppression. (PMID:21443538)
  • A high amino acid charge of the envelope glycoprotein 120 V3 region is important for binding to host CXCR4 receptor. (PMID:21525208)
  • CCR4-, CCR5-, CXCR3-, and selectin ligand-expressing CD4+ T cells preferentially accumulate in the joints of children with juvenile idiopathic arthritis. (PMID:21739422)
  • CCR4+ memory T-cell frequency is increased in patients with Wegener’s granulomatosis with polyangiitis. (PMID:22490506)
  • lymph node metastasis of CCR4(+) HNSCC is promoted by CCL22 in an autocrine or M2-like macrophage-dependent paracrine manner. (PMID:23180648)
  • Authors identify an evolutionarily conserved C-terminal motif in human TTP that directly binds a central domain of CNOT1, a core subunit of the CCR4-NOT complex. (PMID:23644599)
  • CCL17-induced, CCR4-dependent release of CGRP by human airway epithelial cells represents a novel inflammatory pathway in patients with asthma and allergic disease. (PMID:23731651)
  • Anti-CCR4 monoclonal antibody treatment is instrumental for evoking and augmenting antitumor immunity in cancer patients by selectively depleting eTreg cells. (PMID:24127572)
  • CCR4 has a role in tumor aggressive behavior in renal cell carcinoma (PMID:24554520)

Cross-species orthologs

8 orthologs

OrganismSymbolGene ID
danio_rerioccr11.1ENSDARG00000070755
danio_rerioccr2ENSDARG00000079829
danio_reriocabz01093075.1ENSDARG00000086616
danio_rerioccr8.1ENSDARG00000095789
danio_reriosi:ch211-207g17.3ENSDARG00000105363
danio_reriosi:cabz01093077.1ENSDARG00000105467
mus_musculusCcr4ENSMUSG00000047898
rattus_norvegicusCcr4ENSRNOG00000010315

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR3 (ENSG00000144476), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

C-C chemokine receptor type 4 — P51679 (reviewed: P51679)

Alternative names: K5-5

All UniProt accessions (2): P51679, A0N0Q1

UniProt curated annotations — full annotation on UniProt →

Function. High affinity receptor for the C-C type chemokines CCL17/TARC, CCL22/MDC and CKLF isoform 1/CKLF1. The activity of this receptor is mediated by G(i) proteins which activate a phosphatidylinositol-calcium second messenger system. Can function as a chemoattractant homing receptor on circulating memory lymphocytes and as a coreceptor for some primary HIV-2 isolates. In the CNS, could mediate hippocampal-neuron survival.

Subcellular location. Cell membrane.

Tissue specificity. Predominantly expressed in the thymus, in peripheral blood leukocytes, including T-cells, mostly CD4+ cells, and basophils, and in platelets; at lower levels, in the spleen and in monocytes. Detected also in macrophages, IL-2-activated natural killer cells and skin-homing memory T-cells, mostly the ones expressing the cutaneous lymphocyte antigen (CLA). Expressed in brain microvascular and coronary artery endothelial cells.

Post-translational modifications. In natural killer cells, CCL22 binding induces phosphorylation on yet undefined Ser/Thr residues, most probably by beta-adrenergic receptor kinases 1 and 2.

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

RefSeq proteins (1): NP_005499* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000276GPCR_RhodpsnFamily
IPR000355Chemokine_rcptFamily
IPR002239Chemokine_CCR4Family
IPR017452GPCR_Rhodpsn_7TMDomain
IPR050119CCR1-9-likeFamily

Pfam: PF00001

UniProt features (21 total): topological domain 8, transmembrane region 7, glycosylation site 2, sequence variant 2, chain 1, disulfide bond 1

Structure

Experimental structures (PDB)

7 structures.

PDBMethodResolution (Å)
9ULLX-RAY DIFFRACTION, SOLUTION SCATTERING1.63
9ULMX-RAY DIFFRACTION2.01
11TFELECTRON MICROSCOPY3.4
11THELECTRON MICROSCOPY3.5
11TKELECTRON MICROSCOPY3.54
11TDELECTRON MICROSCOPY3.7
11TLELECTRON MICROSCOPY3.9

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-P51679-F180.920.46

Functional residue map

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

Disulfide bonds (1): 110–187

Glycosylation sites (2): 183, 194

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

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

MSigDB gene sets: 163 (showing top): GOBP_TOLERANCE_INDUCTION, GOBP_CELL_CHEMOTAXIS, GOBP_INFLAMMATORY_RESPONSE, GOBP_RESPONSE_TO_PEPTIDE, GOCC_CELL_SURFACE, GOBP_NEUROGENESIS, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN, GOBP_TAXIS, REACTOME_PEPTIDE_LIGAND_BINDING_RECEPTORS, chr3p22, GOBP_NEURON_MIGRATION, MARZEC_IL2_SIGNALING_UP, RYTTCCTG_ETS2_B, GOBP_MULTICELLULAR_ORGANISMAL_LEVEL_HOMEOSTASIS, GOBP_HOMEOSTATIC_PROCESS

GO Biological Process (15): tolerance induction (GO:0002507), chemotaxis (GO:0006935), inflammatory response (GO:0006954), immune response (GO:0006955), positive regulation of cytosolic calcium ion concentration (GO:0007204), calcium-mediated signaling (GO:0019722), homeostasis of number of cells (GO:0048872), cell chemotaxis (GO:0060326), interneuron migration (GO:1904936), neuron migration (GO:0001764), signal transduction (GO:0007165), cell surface receptor signaling pathway (GO:0007166), G protein-coupled receptor signaling pathway (GO:0007186), chemokine-mediated signaling pathway (GO:0070098), cellular response to cytokine stimulus (GO:0071345)

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

GO Cellular Component (3): plasma membrane (GO:0005886), external side of plasma membrane (GO:0009897), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

CategoryPathways
Signaling by GPCR2
Peptide ligand-binding receptors1
GPCR downstream signalling1
Signal Transduction1
GPCR ligand binding1
Class A/1 (Rhodopsin-like receptors)1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
immune system process2
cell migration2
signal transduction2
G protein-coupled receptor signaling pathway2
chemokine binding2
immune system development1
response to chemical1
taxis1
defense response1
response to stimulus1
regulation of biological quality1
intracellular signaling cassette1
multicellular organismal-level homeostasis1
chemotaxis1
cellular response to chemical stimulus1
neuron migration1
generation of neurons1
cell communication1
cellular process1
signaling1
regulation of cellular process1
cellular response to stimulus1
G protein-coupled receptor activity1
cytokine-mediated signaling pathway1
cellular response to chemokine1
response to cytokine1
G protein-coupled chemoattractant receptor activity1
cytokine receptor activity1
chemokine-mediated signaling pathway1
chemokine receptor activity1
C-C chemokine binding1
transmembrane signaling receptor activity1
binding1
membrane1
cell periphery1
plasma membrane1
cell surface1
side of membrane1
cellular anatomical structure1

Protein interactions and networks

STRING

742 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
CCR4CCL22O00626966
CCR4CCL17Q92583936
CCR4CCL2P13500778
CCR4CD4P01730716
CCR4CCL5P13501680
CCR4CCL27Q9Y4X3551
CCR4CD19P15391488
CCR4CNOT8Q9UFF9461
CCR4IL2P01585457
CCR4FOXP3Q9BZS1453
CCR4CD8AP01732446
CCR4IL7RP16871435
CCR4CD28P10747435
CCR4CRYGCP07315427
CCR4CNOT1A5YKK6425

IntAct

44 interactions, top by confidence:

ABTypeScore
TUSC5CCR4psi-mi:“MI:0915”(physical association)0.560
CCL17CCR4psi-mi:“MI:0914”(association)0.500
CCR4CCL17psi-mi:“MI:0915”(physical association)0.500
CCR4RAMP1psi-mi:“MI:0915”(physical association)0.400
RAMP1CCR4psi-mi:“MI:0915”(physical association)0.400
RAMP2CCR4psi-mi:“MI:0915”(physical association)0.400
RAMP3CCR4psi-mi:“MI:0915”(physical association)0.400
CCR4RAMP3psi-mi:“MI:0915”(physical association)0.400
CCR4Cnot7psi-mi:“MI:0915”(physical association)0.400
DHCR24CCR4psi-mi:“MI:0915”(physical association)0.370
ATP2A2CCR4psi-mi:“MI:0915”(physical association)0.370
BSGCCR4psi-mi:“MI:0915”(physical association)0.370
B3GAT3CCR4psi-mi:“MI:0915”(physical association)0.370
CACNA1HCCR4psi-mi:“MI:0915”(physical association)0.370
CCKBRCCR4psi-mi:“MI:0915”(physical association)0.370
CH25HCCR4psi-mi:“MI:0915”(physical association)0.370
CLPTM1CCR4psi-mi:“MI:0915”(physical association)0.370
CNTNAP1CCR4psi-mi:“MI:0915”(physical association)0.370
CDK10CCR4psi-mi:“MI:0915”(physical association)0.370
CLASP2CCR4psi-mi:“MI:0915”(physical association)0.370
ERGIC3CCR4psi-mi:“MI:0915”(physical association)0.370
FXR2CCR4psi-mi:“MI:0915”(physical association)0.370
GHITMCCR4psi-mi:“MI:0915”(physical association)0.370
FAM234ACCR4psi-mi:“MI:0915”(physical association)0.370
NAT14CCR4psi-mi:“MI:0915”(physical association)0.370
NDRG2CCR4psi-mi:“MI:0915”(physical association)0.370
NSUN2CCR4psi-mi:“MI:0915”(physical association)0.370
PRDX1CCR4psi-mi:“MI:0915”(physical association)0.370

BioGRID (37): ZNF335 (Affinity Capture-Western), TUSC5 (Two-hybrid), ADRBK1 (Affinity Capture-Western), ADRBK2 (Affinity Capture-Western), CCR4 (Reconstituted Complex), DHCR24 (Two-hybrid), ATP2A2 (Two-hybrid), BSG (Two-hybrid), B3GAT3 (Two-hybrid), CACNA1H (Two-hybrid), CCKBR (Two-hybrid), CH25H (Two-hybrid), CLPTM1 (Two-hybrid), CNTNAP1 (Two-hybrid), CDK10 (Two-hybrid)

ESM2 similar proteins: A0A4W3GG95, B0F9W3, B3G515, E7FEL0, F7EQ49, O00398, O08878, O46685, O70526, O97665, P25023, P25105, P30411, P32299, P46093, P47774, P49684, P50132, P51679, P51680, P51685, P51686, P55085, P55086, P56484, P79960, Q15743, Q1JQB3, Q1WLP9, Q28642, Q2HJA4, Q2TAD5, Q4KLH9, Q4VA82, Q63645, Q80Z39, Q8BFQ3, Q8BFU7, Q8BLG2, Q8BMP4

Diamond homologs: A0A4W3GG95, A0A6I8PUB9, B2GV46, B5X337, D4A7K7, E7FEL0, E9QJ73, F8VQN3, O00270, O08726, O08858, O14842, O14843, O15529, O42179, O43603, O46685, O60755, O77408, O88410, O88626, O88634, O88853, P21109, P23944, P25024, P25025, P35344, P35383, P35414, P41231, P41232, P46092, P46093, P49652, P49682, P49683, P50132, P51675, P51679

SIGNOR signaling

1 interactions.

AEffectBMechanism
CCL2“up-regulates activity”CCR4binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 36 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 termPartnersFoldFDR
calcium ion transport527.5×3e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic1
Likely pathogenic0
Uncertain significance36
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (1)

Variant IDHGVSClassification
253599GRCh37/hg19 3p24.1-22.3(chr3:29689082-34233218)x1Pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2369 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
3:32953816:A:CS132R0.997
3:32953818:C:AS132R0.997
3:32953818:C:GS132R0.997
3:32953894:A:CS158R0.997
3:32953896:T:AS158R0.997
3:32953896:T:GS158R0.997
3:32953906:T:AW162R0.996
3:32953906:T:CW162R0.996
3:32953731:G:CW103C0.994
3:32953731:G:TW103C0.994
3:32953664:T:CL81P0.993
3:32953789:A:CS123R0.993
3:32953791:T:AS123R0.993
3:32953791:T:GS123R0.993
3:32953662:C:AN80K0.991
3:32953662:C:GN80K0.991
3:32953729:T:AW103R0.991
3:32953729:T:CW103R0.991
3:32953981:T:AC187S0.991
3:32953982:G:CC187S0.991
3:32953593:T:AN57K0.990
3:32953593:T:GN57K0.990
3:32953676:A:CD85A0.990
3:32953677:T:AD85E0.989
3:32953677:T:GD85E0.989
3:32953750:T:AC110S0.989
3:32953751:G:CC110S0.989
3:32953679:T:CL86P0.988
3:32953780:G:CG120R0.987
3:32953579:G:CG53R0.986

dbSNP variants (sampled 300 via entrez): RS1000863052 (3:32952484 C>T), RS1000927514 (3:32952981 A>G), RS1001107718 (3:32952712 G>C,T), RS1001163787 (3:32956008 T>C), RS1001455593 (3:32951758 C>T), RS1001599783 (3:32950672 C>T), RS1003425078 (3:32954956 C>G), RS1003504908 (3:32954710 T>G), RS1003885384 (3:32955288 G>T), RS1004562012 (3:32956654 G>T), RS1004623888 (3:32955502 A>G), RS1004700618 (3:32956161 G>T), RS1004713335 (3:32950954 C>A,T), RS1005807083 (3:32950539 T>A), RS1007312011 (3:32950925 A>C)

Disease associations

OMIM: gene MIM:604836 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2414 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

7 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 199,915 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

MoleculeNamePhasePatents
CHEMBL104CLOTRIMAZOLE456,325
CHEMBL633AMIODARONE429,704
CHEMBL64391ITRACONAZOLE4606
CHEMBL964DISULFIRAM438,611
CHEMBL50QUERCETIN374,559
CHEMBL2105686CENICRIVIROC MESYLATE185
CHEMBL2178575GSK-2239633125

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 (9 total), top 9:

LigandActionAffinityParameter
CCL22Full agonist9.2pIC50
CCL17Full agonist8.7pIC50
AZD1678Antagonist8.5pIC50
GSK2239633AAntagonist7.83pIC50
compound 8ic [PMID: 19081254]Antagonist7.74pIC50
AZD2098Antagonist7.6pIC50
compound 31 [PMID: 31259550]Antagonist7.4pIC50
FLX475Antagonist7.0pIC50
zelnecirnonAntagonist7.0pIC50

Binding affinities (BindingDB)

52 measured of 90 human assays (90 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

LigandMeasureValuePatent
ethyl 1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-methyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carboxylateIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-methyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-(3-methyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-ethyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-ethyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-methyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-ethyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
ethyl 1-[(2,4-dichlorophenyl)methyl]-6-(3-methyl-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carboxylateIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(3R,4S)-4-(2,5-dihydropyrrol-1-yl)-3-methylpiperidin-1-yl]-3-methylpyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(2S)-2,5-dimethyl-4-pyrrolidin-1-ylpiperidin-1-yl]-3-methylpyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(2S,4S,5R)-2,5-dimethyl-4-pyrrolidin-1-ylpiperidin-1-yl]-3-methylpyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methyl-6-[(3R,4S)-3-methyl-4-[(2S)-2-methylpyrrolidin-1-yl]piperidin-1-yl]pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-(3-fluoro-4-piperidin-1-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazine-3-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[1-(2,4-dichlorophenyl)ethyl]-6-[3-(hydroxymethyl)-4-piperidin-1-ylpiperidin-1-yl]pyrazolo[3,4-b]pyrazine-3-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(3S,4R)-3-(hydroxymethyl)-4-piperidin-1-ylpiperidin-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methyl-6-[4-[(2R)-2-methylpyrrolidin-1-yl]piperidin-1-yl]pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
(2S)-1-[(3R,4S)-1-[3-cyano-1-[(1R)-1-(2,4-dichlorophenyl)ethyl]pyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidine-2-carboxylic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
2-[(2S)-1-[(3R,4S)-1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]propan-2-olIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methyl-6-[(3R,4S)-3-methyl-4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(3R)-3-methyl-4-[(3R)-3-methylpiperidin-1-yl]piperidin-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-[(2S)-1-[(3R)-1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]propanoic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
2-[(2S)-1-[(3R)-1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]ethanamineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
4-[(2S)-1-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]-1,1,1-trifluorobutan-2-olIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-[(2S)-1-[(3R)-1-[1-[(1R)-1-(4-chloro-2-fluorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]propanoic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-[(2S)-1-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]piperidin-4-yl]pyrrolidin-2-yl]propanoic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
2-[(2S)-1-[(3S)-1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]ethanesulfonamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-((2S)-1-(1-(1-((R)-1-(2,4-Dichlorophenyl)ethyl)-3-methyl-1H-pyrazolo[3,4-b]pyrazin-6-yl)-3-methylpiperidin-4-yl)pyrrolidin-2-yl)-2-fluoropropanoic acid 2,2,2-trifluoroacetate (major diastereomer)IC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-[(2S)-1-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]-2-hydroxypropanoic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-[(2S)-1-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-3-methylpiperidin-4-yl]pyrrolidin-2-yl]butanoic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[4-(4-fluoropiperidin-1-yl)-3-methylpiperidin-1-yl]-3-methylpyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[4-[3-(hydroxymethyl)piperidin-1-yl]piperidin-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
(3R)-1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]piperidine-3-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
[(3R)-1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-4-[(3R)-3-methylpiperidin-1-yl]piperidin-3-yl]methanolIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methyl-6-(3-methyl-4-piperidin-3-ylpiperidin-1-yl)pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[4-(1-ethylpiperidin-3-yl)-3-methylpiperidin-1-yl]-3-methylpyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
[(2S)-1-[4-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]cyclohex-3-en-1-yl]pyrrolidin-2-yl]methanolIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(3R,4S)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-3-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
(2S)-1-[4-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-6-methylcyclohex-3-en-1-yl]pyrrolidine-2-carboxylic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
3-[(2S)-1-[4-[3-cyano-1-[(1R)-1-(2,4-dichlorophenyl)ethyl]pyrazolo[3,4-b]pyrazin-6-yl]-2-methylcyclohex-3-en-1-yl]pyrrolidin-2-yl]propanoic acidIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[(5S)-4-[(2S)-2-(hydroxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
(2S)-1-[(6S)-4-[3-cyano-1-[(1R)-1-(2,4-dichlorophenyl)ethyl]pyrazolo[3,4-b]pyrazin-6-yl]-6-methylcyclohex-3-en-1-yl]pyrrolidine-2-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
6-[(5R)-4-[(2S)-2-(aminomethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]-1-[(1R)-1-(2,4-dichlorophenyl)ethyl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
N-[[(2S)-1-[(6R)-4-[3-cyano-1-[(1R)-1-(2,4-dichlorophenyl)ethyl]pyrazolo[3,4-b]pyrazin-6-yl]-6-methylcyclohex-3-en-1-yl]pyrrolidin-2-yl]methyl]methanesulfonamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[4-[(2S)-2-(methoxymethyl)pyrrolidin-1-yl]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[5-methyl-4-[(2R)-2-methylpyrrolidin-1-yl]cyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
(2S)-1-[(6R)-4-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]-6-methylcyclohex-3-en-1-yl]pyrrolidine-2-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[5-methyl-4-[(2R)-2-methylpyrrolidin-1-yl]cyclohexen-1-yl]-3-(trifluoromethyl)pyrazolo[3,4-b]pyrazineIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
[(2S)-1-[4-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-(trifluoromethyl)pyrazolo[3,4-b]pyrazin-6-yl]-6-methylcyclohex-3-en-1-yl]pyrrolidin-2-yl]methanolIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
(2S)-1-[(1S,6R)-4-[3-cyano-1-[(1R)-1-(2,4-dichlorophenyl)ethyl]pyrazolo[3,4-b]pyrazin-6-yl]-6-methylcyclohex-3-en-1-yl]-N-methylpyrrolidine-2-carboxamideIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[4-[ethyl-[(3-hydroxyoxetan-3-yl)methyl]amino]-5-methylcyclohexen-1-yl]pyrazolo[3,4-b]pyrazine-3-carbonitrileIC50300 nMUS-10246462: Chemokine receptor modulators and uses thereof

ChEMBL bioactivities

698 potent at pChembl≥5 of 749 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChemblTypeValueUnitMolecule
9.50IC500.3162nMCHEMBL4172769
9.20IC500.631nMCHEMBL4167445
9.10Ki0.7943nMCHEMBL2018953
9.00Ki1nMCHEMBL3797662
9.00IC501nMCHEMBL4162364
8.80Ki1.585nMCHEMBL3799266
8.60Ki2.512nMCHEMBL372399
8.60Ki2.512nMCHEMBL3797537
8.60IC502.512nMCHEMBL4160218
8.60IC502.512nMCHEMBL4172635
8.52IC503nMCHEMBL233046
8.50Ki3.162nMCHEMBL2018954
8.50Ki3.162nMCHEMBL3799578
8.41IC503.89nMCHEMBL2018954
8.40Ki3.981nMCHEMBL3798452
8.40IC503.981nMCHEMBL4172635
8.40IC503.981nMCHEMBL4175323
8.40IC503.981nMCHEMBL4160846
8.40IC503.981nMCHEMBL4173046
8.30Ki5.012nMCHEMBL3799393
8.26IC505.495nMCHEMBL2018953
8.22IC506nMCHEMBL4641127
8.20IC506.31nMCHEMBL2326625
8.20IC506.31nMCHEMBL2326611
8.20EC506.31nMCHEMBL3799393
8.15IC507nMCHEMBL233046
8.14IC507.2nMCHEMBL3901913
8.10Ki7.943nMCHEMBL2018968
8.10IC507.943nMCHEMBL372399
8.10IC507.943nMCHEMBL3799266
8.10IC507.943nMCHEMBL3799578
8.10IC507.943nMCHEMBL3797662
8.10IC507.943nMCHEMBL4173861
8.10IC507.943nMCHEMBL4165356
8.10IC508nMCHEMBL4642563
8.09IC508.1nMCHEMBL3904195
8.05IC509nMCHEMBL4637695
8.03IC509.4nMCHEMBL3952996
8.00Ki10nMCHEMBL2018969
8.00Ki10nMGSK-2239633
8.00EC5010nMCHEMBL2018953
8.00IC5010nMCHEMBL372399
8.00IC5010nMCHEMBL4170431
7.90IC5012.59nMCHEMBL2018968
7.90Ki12.59nMCHEMBL2018964
7.90IC5012.59nMCHEMBL2326630
7.90IC5012.59nMCHEMBL2321924
7.90EC5012.59nMCHEMBL3798452
7.90IC5012.59nMCHEMBL4165939
7.90IC5012.59nMCHEMBL4162097

PubChem BioAssay actives

651 with measured affinity, of 1100 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.

CompoundAssayTypeValueUnit
2,3-dichloro-N-[5-chloro-3-[[2-(hydroxymethyl)phenyl]methoxy]pyrazin-2-yl]benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0003uM
2,3-dichloro-N-[5-chloro-3-(pyridin-3-ylmethoxy)pyrazin-2-yl]benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0006uM
[4-[4-[(2,4-dichlorophenyl)methylamino]pyrido[2,3-d]pyrimidin-2-yl]piperazin-1-yl]-[(2R)-piperidin-2-yl]methanone655598: Displacement of [125I]TARC from human CCR4 expressed in CHO membranes by SPAki0.0008uM
N-[(2,4-dichlorophenyl)methyl]-N-methyl-2-[2-(pyrrolidin-2-ylmethyl)-2,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-amine1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0010uM
2,3-dichloro-N-(5,6-difluoro-3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0010uM
N-[(2,4-dichlorophenyl)methyl]-2-[2-(pyrrolidin-2-ylmethyl)-2,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-amine1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0016uM
[4-[4-[(2,4-dichlorophenyl)methylamino]pyrimidin-2-yl]piperazin-1-yl]-[(2R)-piperidin-2-yl]methanone1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0025uM
N-[(2,4-dichlorophenyl)methyl]-2-[2-(piperidin-2-ylmethyl)-2,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-amine1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0025uM
2,3-dichloro-N-(5-fluoro-3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0025uM
2,3-dichloro-N-(5-chloro-3-prop-2-ynoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0025uM
[4-[4-[(2,4-dichlorophenyl)methylamino]pyrido[2,3-d]pyrimidin-2-yl]piperazin-1-yl]-[(2S)-piperidin-2-yl]methanone292928: Antagonist activity at human CCR4 expressed in CEMS529 cells assessed as effect on calcium mobilizationic500.0030uM
N-[(2,4-difluorophenyl)methyl]-2-[2-(pyrrolidin-2-ylmethyl)-2,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-amine1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0032uM
N-[5-bromo-3-[[3-[2-(dimethylamino)ethoxy]-4-methoxyphenyl]methoxy]pyrazin-2-yl]-4-methylbenzenesulfonamide1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0032uM
N-[(2,4-dichlorophenyl)methyl]-2-[2-[[(2S)-pyrrolidin-2-yl]methyl]-2,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-amine1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0040uM
2,3-dichloro-N-(6-fluoro-3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0040uM
2,3-dichloro-N-[6-chloro-5-(hydroxymethyl)-3-methoxypyrazin-2-yl]benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0040uM
N-[3-[(3-bromophenyl)methoxy]-5-chloropyrazin-2-yl]-2,3-dichlorobenzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0040uM
N-[(2,4-dichlorophenyl)methyl]-2-[2-[[(2R)-pyrrolidin-2-yl]methyl]-2,8-diazaspiro[4.5]decan-8-yl]pyrimidin-4-amine1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0050uM
N-[2-[(3R)-3-[1-[1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-3-methylpyrazolo[3,4-b]pyrazin-6-yl]azetidin-3-yl]piperidin-1-yl]ethyl]acetamide1669404: Antagonist activity at human CCR4 expressed in rat chem-5 cells assessed as inhibition of CCL22-induced calcium flux measured at 2.5 secs time interval for 45 secs by calcium 6 dye-based FLIPR assayic500.0060uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-(hydroxymethyl)indazol-1-yl]methyl]phenyl]methyl]acetamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0063uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-4-methylmorpholine-3-carboxamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0063uM
2,3-dichloro-N-(6-chloro-3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0079uM
3,4-dichloro-N-(5-chloro-3-methoxypyrazin-2-yl)thiophene-2-sulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0079uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-hydroxypropanamide655598: Displacement of [125I]TARC from human CCR4 expressed in CHO membranes by SPAki0.0079uM
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[3-[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]azetidin-1-yl]pyrazolo[3,4-b]pyrazine-3-carboxamide1669404: Antagonist activity at human CCR4 expressed in rat chem-5 cells assessed as inhibition of CCL22-induced calcium flux measured at 2.5 secs time interval for 45 secs by calcium 6 dye-based FLIPR assayic500.0080uM
1-[(1R)-1-(2,4-dichlorophenyl)ethyl]-6-[3-[(3R)-1-(2-hydroxyethyl)piperidin-3-yl]azetidin-1-yl]-N,N-dimethylpyrazolo[3,4-b]pyrazine-3-carboxamide1669404: Antagonist activity at human CCR4 expressed in rat chem-5 cells assessed as inhibition of CCL22-induced calcium flux measured at 2.5 secs time interval for 45 secs by calcium 6 dye-based FLIPR assayic500.0090uM
N-(5-bromo-3-methoxypyrazin-2-yl)-2,3-dichlorobenzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0100uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-hydroxy-2-methylpropanamide655598: Displacement of [125I]TARC from human CCR4 expressed in CHO membranes by SPAki0.0100uM
N-[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]-2-hydroxyacetamide707906: Binding affinity to CCR4ki0.0100uM
2,3-dichloro-N-[5-chloro-3-(pyrimidin-5-ylmethoxy)pyrazin-2-yl]benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0126uM
2,3-dichloro-N-(5-chloro-3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0126uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-hydroxyindazol-1-yl]methyl]phenyl]methyl]acetamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0126uM
2,3-dichloro-N-(5-ethoxy-3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0126uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-5-fluoro-4-methoxyindazol-1-yl]methyl]phenyl]methyl]acetamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0126uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]acetamide655598: Displacement of [125I]TARC from human CCR4 expressed in CHO membranes by SPAki0.0126uM
4-N-cycloheptyl-2-N-cyclopentyl-6,7-dimethoxyquinazoline-2,4-diamine343856: Antagonist activity at human CCR4 receptor expressed in mouse B300-19 cells by [35S]GTPgammaS binding assayic500.0130uM
N-cycloheptyl-7-methoxy-2-(4-pyrrolidin-1-ylpiperidin-1-yl)quinazolin-4-amine343856: Antagonist activity at human CCR4 receptor expressed in mouse B300-19 cells by [35S]GTPgammaS binding assayic500.0130uM
4-[[cyclohexylmethyl-[[2-(trifluoromethyl)phenyl]methyl]amino]methyl]-N-naphthalen-1-yl-1,3-thiazol-2-amine264000: Displacement of [125I]TARC from CCR4 expressed in human CEM cell lineic500.0140uM
2,3-dichloro-N-(3-methoxypyrazin-2-yl)benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0158uM
2-chloro-N-(5-chloro-3-methoxypyrazin-2-yl)-3-fluorobenzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0158uM
[8-[4-[(2,4-dichlorophenyl)methylamino]pyrimidin-2-yl]-2,8-diazaspiro[4.5]decan-2-yl]-[(2R)-pyrrolidin-2-yl]methanone1296777: Displacement of [125I]-TARC from human recombinant CCR4 expressed in CHO cell membranes by scintillation counting methodki0.0158uM
2,3-dichloro-N-[5-chloro-3-(2-methylpropoxy)pyrazin-2-yl]benzenesulfonamide1502609: Antagonist activity at recombinant human CCR4 expressed in CHO-K1 cells assessed as inhibition of CCL22 induced Ca2+ mobilization after 2 hrs by FMAT based fluorescence assayic500.0158uM
N-[[3-[[3-[(3-fluoro-4-methylphenyl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-hydroxy-2-methylpropanamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0158uM
(3S)-N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]morpholine-3-carboxamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0158uM
(2R)-N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-(methylamino)propanamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0158uM
2-amino-N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-methylpropanamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0158uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-hydroxyacetamide655598: Displacement of [125I]TARC from human CCR4 expressed in CHO membranes by SPAki0.0158uM
N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-6-fluoro-4-methoxyindazol-1-yl]methyl]phenyl]methyl]-2-hydroxy-2-methylpropanamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0158uM
(2S)-N-[[3-[[3-[(5-chlorothiophen-2-yl)sulfonylamino]-4-methoxyindazol-1-yl]methyl]phenyl]methyl]piperidine-2-carboxamide728788: Antagonist activity at human recombinant CCR4 receptor expressed in CHO cell membranes by [35S]GTPgammaS binding assayic500.0158uM
4-[[bis(cyclohexylmethyl)amino]methyl]-N-naphthalen-1-yl-1,3-thiazol-2-amine264000: Displacement of [125I]TARC from CCR4 expressed in human CEM cell lineic500.0180uM

CTD chemical–gene interactions

26 total (human), top 26 by PubMed support.

ChemicalActions (top 5)PubMed papers
bisphenol Aincreases methylation1
deoxynivalenolincreases expression1
kojic aciddecreases expression1
3,3’-diindolylmethaneaffects methylation1
sulforaphaneaffects methylation1
1-nitropyreneincreases expression1
S-(1,2-dichlorovinyl)cysteinedecreases reaction, increases expression1
fumonisin B1increases expression1
perfluorooctane sulfonic aciddecreases expression1
CGP 52608increases reaction, affects binding1
N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochlorideaffects cotreatment, decreases expression, decreases reaction1
abrineincreases expression1
Fingolimod Hydrochloridedecreases expression1
Decitabineaffects expression1
Arsenicaffects expression1
Asbestosincreases expression1
Benzo(a)pyreneincreases methylation1
Calciumaffects abundance1
Dexamethasoneincreases expression1
Endosulfandecreases expression1
Lipopolysaccharidesincreases expression, decreases reaction1
Mevalonic Aciddecreases reaction, increases expression1
Ozoneincreases expression1
Zearalenoneincreases expression1
Simvastatindecreases reaction, increases expression1
Hydrolyzable Tanninsdecreases reaction, affects cotreatment, decreases expression1

ChEMBL screening assays

152 unique, capped per target: 98 binding, 54 functional

Representative assays (with source publication via chembl_document):

Assay IDTypeDescriptionSource paper
CHEMBL1003795BindingDisplacement of [125I]TARC from human CCR4 expressed in CHO cells at 10 uMSynthesis and structure-activity relationship of benzetimide derivatives as human CXCR3 antagonists. — Bioorg Med Chem Lett
CHEMBL1020783FunctionalAntagonist activity at human CCR4 receptor expressed in mouse B300-19 cells assessed as CCL22-induced [35S]GTPgammaS bindingPotent and orally bioavailable CCR4 antagonists: Synthesis and structure-activity relationship study of 2-aminoquinazolines. — Bioorg Med Chem

Cellosaurus cell lines

9 cell lines: 7 cancer cell line, 2 spontaneously immortalized cell line

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

CellosaurusNameCategorySex
CVCL_1D97HOS-CD4-CCR4Cancer cell lineFemale
CVCL_B8CNAbcam HCT 116 CCR4 KOCancer cell lineMale
CVCL_B8TGAbcam MCF-7 CCR4 KOCancer cell lineFemale
CVCL_B9EWAbcam A-549 CCR4 KOCancer cell lineMale
CVCL_E6P5Genomeditech CHO-K1 H_CCR4Spontaneously immortalized cell lineFemale
CVCL_KW58PathHunter CHO-K1 CCR4 beta-arrestinSpontaneously immortalized cell lineFemale
CVCL_KZ95PathHunter U2OS CCR4 Total GPCR InternalizationCancer cell lineFemale
CVCL_S497GHOST(3).CCR4Cancer cell lineFemale
CVCL_ZK01Tango CCR4-bla U2OSCancer cell lineFemale

Clinical trials (associated diseases)

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

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

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Sources 81

This page pulls from 81 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_assaychembl_documentchembl_moleculechembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgtopdb_interactiongwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpatentpatent_compoundpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot