ACKR3

Summary

ACKR3 (atypical chemokine receptor 3, HGNC:23692) is a protein-coding gene on chromosome 2q37.3, encoding Atypical chemokine receptor 3 (P25106). Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis.

This gene encodes a member of the G-protein coupled receptor family. Although this protein was earlier thought to be a receptor for vasoactive intestinal peptide (VIP), it is now considered to be an orphan receptor, in that its endogenous ligand has not been identified. The protein is also a coreceptor for human immunodeficiency viruses (HIV). Translocations involving this gene and HMGA2 on chromosome 12 have been observed in lipomas.

Source: NCBI Gene 57007 — RefSeq curated summary.

At a glance

• Gene–disease (curated): oculomotor-abducens synkinesis (Moderate, GenCC)
• GWAS associations: 10
• Clinical variants (ClinVar): 89 total — 34 pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 1 cancer types
• MANE Select transcript: NM_020311

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:23692
Approved symbol	ACKR3
Name	atypical chemokine receptor 3
Location	2q37.3
Locus type	gene with protein product
Status	Approved
Aliases	RDC1, GPR159
Ensembl gene	ENSG00000144476
Ensembl biotype	protein_coding
OMIM	610376
Entrez	57007

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 9 protein_coding

ENST00000272928, ENST00000447924, ENST00000929731, ENST00000946093, ENST00000946094, ENST00000946095, ENST00000946096, ENST00000946097, ENST00000946098

RefSeq mRNA: 1 — MANE Select: NM_020311 NM_020311

CCDS: CCDS2516

Canonical transcript exons

ENST00000272928 — 2 exons

Exon	Start	End
ENSE00000965340	236580440	236582354
ENSE00001333006	236569825	236569924

Expression profiles

Bgee: expression breadth ubiquitous, 278 present calls, max score 99.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.4503 / max 914.7256, expressed in 1309 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
26215	64.7189	1278
26214	0.6178	291
26213	0.4025	243
26218	0.2686	154
202621	0.2242	138
26216	0.2062	120
26212	0.0121	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
synovial joint	UBERON:0002217	99.50	gold quality
vena cava	UBERON:0004087	99.36	gold quality
tendon of biceps brachii	UBERON:0008188	98.92	gold quality
cartilage tissue	UBERON:0002418	98.43	gold quality
skin of hip	UBERON:0001554	98.22	gold quality
saphenous vein	UBERON:0007318	98.19	gold quality
blood vessel layer	UBERON:0004797	98.16	gold quality
pericardium	UBERON:0002407	97.89	gold quality
layer of synovial tissue	UBERON:0007616	97.23	gold quality
popliteal artery	UBERON:0002250	97.03	gold quality
tibial artery	UBERON:0007610	97.03	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.78	gold quality
aorta	UBERON:0000947	96.26	gold quality
tendon	UBERON:0000043	96.03	gold quality
mucosa of stomach	UBERON:0001199	95.91	gold quality
adipose tissue	UBERON:0001013	95.81	gold quality
subcutaneous adipose tissue	UBERON:0002190	95.78	gold quality
connective tissue	UBERON:0002384	95.54	gold quality
superficial temporal artery	UBERON:0001614	95.42	gold quality
calcaneal tendon	UBERON:0003701	95.40	gold quality
ascending aorta	UBERON:0001496	95.37	gold quality
urethra	UBERON:0000057	95.35	gold quality
thoracic aorta	UBERON:0001515	95.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	95.19	gold quality
omental fat pad	UBERON:0010414	95.13	gold quality
peritoneum	UBERON:0002358	95.08	gold quality
tibia	UBERON:0000979	94.66	gold quality
nerve	UBERON:0001021	94.62	gold quality
tibial nerve	UBERON:0001323	94.62	gold quality
parietal pleura	UBERON:0002400	94.38	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 5.

Experiment	Marker?	Max mean expression
E-MTAB-7008	yes	289.28
E-GEOD-109979	yes	281.67
E-ANND-3	yes	27.42
E-GEOD-135922	yes	21.50
E-MTAB-6678	yes	13.34
E-GEOD-86618	no	617.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ARX, CTCF, EBF3, EGR1, ESR1, ETS2, HIC1, HIF1A, NFKB, NRF1, PAX3

miRNA regulators (miRDB)

71 targeting ACKR3, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-539-5P	99.93	70.30	2855
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-383-3P	99.85	65.84	1359
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6817-3P	99.79	68.35	2126
HSA-MIR-548AG	99.77	69.25	1492
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-200A-5P	99.76	69.10	949
HSA-MIR-200B-5P	99.76	69.05	948
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-548AI	99.69	69.24	1494

Literature-anchored findings (GeneRIF, showing 40)

• RDC1, which we propose to rename as CXCR7, is a receptor for CXCL12 (PMID:16107333)
• RDC1 is a marker for memory B cells, which are competent to become antibody-secreting cells (PMID:16455976)
• characterization of CXCR7, which binds with high affinity to SDF-1 & I-TAC; CXCR7 has properties that affect a spectrum of biological & pathological processes, including cell growth/survival and adhesion, as well as promotion of tumor growth (PMID:16940167)
• CD13 rapidly processed CXCL11, but not CXCL8, to generate truncated CXCL11 forms that had reduced binding, signaling, and chemotactic properties for lymphocytes and CXCR3- or CXCR7-transfected cells. (PMID:17363734)
• CXCR7 has key functions in promoting breast and lung tumor development and progression. (PMID:17898181)
• Transcripts of CXCR7 were detected within tumor cells and tumor free lungs, mainly in alveolar macrophage. (PMID:18214534)
• Although CXCR7 is not an intrinsic signaling receptor for CXCL12 on lymphocytes or CD34(+) cells, its blocking can be useful for therapeutic interference with CXCR4-mediated activation of integrins. (PMID:18653785)
• differential expression in early and late term human placenta (PMID:18956235)
• Higher expression of CXCR7 is associated with Rec-Distant and poor DFS in patients with p-stage I NSCLC. (PMID:19309748)
• The tumor suppressor HIC1 is implicated in the transcriptional regulation of the chemokine receptor CXCR7, a key player in the promotion of tumorigenesis in a wide variety of cell types. (PMID:19525223)
• Although CXCR7 is dispensable for bare filter in vitro chemotaxis, CXCR7 plays an essential role in the CXCL12/CXCR4-mediated transendothelial migration of CXCR4-positive CXCR7-positive human tumor cells. (PMID:19641136)
• Data show that beta-arrestin 2 increased uptake of CXCL12 in cells expressing CXCR7, emphasizing the functional relevance of the interaction between CXCR7 and beta-arrestin 2. (PMID:19794961)
• Vascular smooth muscle cells that endogenously express CXCR7 migrate to its ligand interferon-inducible T-cell alpha chemoattractant. (PMID:20018651)
• Studies indicate that CXCR7 is an interceptor for CXCL12 and CXCL11. (PMID:20036838)
• SDF-1 binding receptors CXCR4 & CXCR7 are differently regulated in rhabdomyosarcom (RMS)cells; upregulation of CXCR4 & downregulation of CXCR7 by PAX3-FKHR or hypoxia may give SDF-1 an advantage to engage CXCR4 receptor, thus increasing RMS motility (PMID:20068066)
• expression up-regulated in polyp tissue of chronic rhinosinusitis (PMID:20109310)
• Data show that CXCR7 continuously cycles between the plasma membrane and intracellular compartments in the absence and presence of ligand. (PMID:20161793)
• CXCR7 plays a key role during C. pneumoniae entry. The combination knockdown of CXCR7, ITGB2, and PDGFB significantly inhibits C. pneumoniae entry. (PMID:20233927)
• CXCR7 regulates the invasion, angiogenesis and tumor growth of hepatocellular carcinoma cells (PMID:20380740)
• CXCR7 is found on “differentiated” glioma cells, and the alternate receptor CXCR4 is also localized on glioma stem-like cells (PMID:20388803)
• The report for the first time that high CXCR7 expression preferentially associates with poor patient survival of Ewing’s sarcoma. (PMID:20525755)
• The expression and function of CXCR3 and CXCR7 receptors in cervical carcinoma, rhabdomyosarcoma and glioblastoma cell lines, was evaluated. (PMID:20529825)
• In patients with renal cell carcinoma, level of CXCR7 and CXCR4 expression in tumor tissue correlated with disease free survival and lymphatic metastasis; higher CXCR7 and CXCR4 expression predicts earlier relapse. (PMID:20578990)
• CXCR7 is important for angiogenesis in rheumatoid arthritis synovium (PMID:20617529)
• The autocrine/paracrine macrophage migration inhibitory factor (MIF)/chemokines CXCR4/CXCR7 axis plays an important pleiotropic role in rhabdomyosarcoma growth. (PMID:20861157)
• CXCR7: a new SDF-1-binding receptor in contrast to normal CD34(+) progenitors is functional and is expressed at higher level in human malignant hematopoietic cells. (PMID:20887389)
• whereas CXCR7 protein is expressed by primitive RBCs during murine embryonic development, in adult mammals CXCR7 protein is not expressed by normal peripheral blood cells. (PMID:20889540)
• CXCR4 and CXCR7 cores share ligand-binding surfaces for the binding of the synthetic ligands, indicating that CXCR4 inhibitors should be tested also on CXCR7. (PMID:20956518)
• The results of this study highlight the preferential CXCR7 and CXCL12 expression within more aggressive tumors and the possible role of CXCR7 in meningioma vascularization. (PMID:21316111)
• Studies indicate that CXCL12 binds to CXCR4 and CXCR7 and promote cell survival. (PMID:21349998)
• Results reveal a novel mechanism of ligand-independent growth promotion by CXCR7 and its coregulation by the proinflammatory factor IL-8 in prostate cancer. (PMID:21398406)
• High expression of CXCR7 combined with Alpha fetoprotein in hepatocellular carcinoma correlates with extra-hepatic metastasis to lung after hepatectomy. (PMID:21627360)
• Data suggest that CXCR7 may interact with CXCR4 at the intracellular level, possibly affecting CXCR4 trafficking and/or coupling to other proteins. (PMID:21655198)
• 17-beta-estradiol-regulation of the CXCL12 axis components and their involvement in the growth of breast cancer cells (PMID:21695171)
• CXCR7/CXCR4 heterodimer constitutively recruits beta-arrestin to enhance cell migration. (PMID:21730065)
• The CXCL11/CXCR7 pathway is involved hepatocellular carcinoma progression. (PMID:21778049)
• the C-terminus of EBNA-2 accounts for the greater ability of type 1 EBV to promote B cell proliferation, through mechanisms that include higher induction of genes (LMP-1 and CXCR7) required for proliferation and survival of EBV-LCLs. (PMID:21857817)
• Neuroblastoma expressed both of the SDF-1 receptors CXCR4 and CXCR7. shRNA knockdown showed that these receptors were responsible for the migration of neuroblastoma towards mesenchymal stromal cells. (PMID:21906874)
• High expression of CXCR7 is associated with gallbladder cancer. (PMID:21986127)
• CXCL12, on binding CXCR7, induced phosphorylation of extra cellular regulated protein kinases (ERK 1/2) and Akt. (PMID:22070874)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	ackr3b	ENSDARG00000058179
danio_rerio	ackr3a	ENSDARG00000062478
mus_musculus	Ackr3	ENSMUSG00000044337
rattus_norvegicus	Ackr3	ENSRNOG00000019622
caenorhabditis_elegans		WBGENE00011578

Paralogs (23): CCR6 (ENSG00000112486), CCRL2 (ENSG00000121797), CCR2 (ENSG00000121807), CXCR4 (ENSG00000121966), CCR7 (ENSG00000126353), ACKR4 (ENSG00000129048), ACKR2 (ENSG00000144648), RGR (ENSG00000148604), CXCR5 (ENSG00000160683), CCR5 (ENSG00000160791), CXCR1 (ENSG00000163464), CCR1 (ENSG00000163823), CX3CR1 (ENSG00000168329), CXCR6 (ENSG00000172215), XCR1 (ENSG00000173578), CCR9 (ENSG00000173585), CCR8 (ENSG00000179934), CXCR2 (ENSG00000180871), GALR2 (ENSG00000182687), CCR3 (ENSG00000183625), CCR4 (ENSG00000183813), CCR10 (ENSG00000184451), CXCR3 (ENSG00000186810)

Protein

Protein identifiers

Atypical chemokine receptor 3 — P25106 (reviewed: P25106)

Alternative names: C-X-C chemokine receptor type 7, Chemokine orphan receptor 1, G-protein coupled receptor 159, G-protein coupled receptor RDC1 homolog

All UniProt accessions (2): P25106, A0A140T9K6

UniProt curated annotations — full annotation on UniProt →

Function. Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CXCL11 and CXCL12/SDF1. Chemokine binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization and activation of MAPK signaling pathway. Required for regulation of CXCR4 protein levels in migrating interneurons, thereby adapting their chemokine responsiveness. In glioma cells, transduces signals via MEK/ERK pathway, mediating resistance to apoptosis. Promotes cell growth and survival. Not involved in cell migration, adhesion or proliferation of normal hematopoietic progenitors but activated by CXCL11 in malignant hemapoietic cells, leading to phosphorylation of ERK1/2 (MAPK3/MAPK1) and enhanced cell adhesion and migration. Plays a regulatory role in CXCR4-mediated activation of cell surface integrins by CXCL12. Required for heart valve development. Regulates axon guidance in the oculomotor system through the regulation of CXCL12 levels. Acts as a receptor for SHLP2, mediating its effects on activation of proopiomelanocortin neurons in the arcuate nucleus of the hypothalamus which leads to suppression of food intake and increased energy expenditure. (Microbial infection) Acts as a coreceptor with CXCR4 for a restricted number of HIV isolates.

Subunit / interactions. Homodimer. Can form heterodimers with CXCR4; heterodimerization may regulate CXCR4 signaling activity. Interacts with ARRB1 and ARRB2. (Microbial infection) Interacts with Kaposi virus protein vCCL2.

Subcellular location. Cell membrane. Early endosome. Recycling endosome.

Tissue specificity. Expressed in monocytes, basophils, B-cells, umbilical vein endothelial cells (HUVEC) and B-lymphoblastoid cells. Lower expression detected in CD4+ T-lymphocytes and natural killer cells. In the brain, detected in endothelial cells and capillaries, and in mature neurons of the frontal cortex and hippocampus. Expressed in tubular formation in the kidney. Highly expressed in astroglial tumor endothelial, microglial and glioma cells. Expressed at low levels in normal CD34+ progenitor cells, but at very high levels in several myeloid malignant cell lines. Expressed in breast carcinomas but not in normal breast tissue (at protein level).

Post-translational modifications. The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated. Ubiquitinated at the Lys residues in its C-terminal cytoplasmic tail and is essential for correct trafficking from and to the cell membrane. Deubiquitinated by CXCL12-stimulation in a reversible manner.

Disease relevance. Oculomotor-abducens synkinesis (OCABSN) [MIM:619215] An autosomal recessive disorder characterized by ptosis and elevation of the eyelid on ipsilateral abduction. OCABSN features are consistent with abnormal innervation of the levator palpebrae superioris muscle, which raises the eyelid, and the lateral rectus muscle, which controls lateral eye movement. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal cytoplasmic tail, plays a key role in: correct trafficking to the cell membrane, recruitment of beta-arrestin, ubiquitination, and in chemokine scavenging and signaling functions. The Ser/Thr residues and the Lys residues in the C-terminal cytoplasmic tail are essential for beta-arrestin recruitment and ubiquitination respectively.

Induction. Up-regulated during cell differentiation in glioma cells.

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

RefSeq proteins (1): NP_064707* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000276	GPCR_Rhodpsn	Family
IPR001416	ACKR3	Family
IPR017452	GPCR_Rhodpsn_7TM	Domain
IPR047143	GPER1-like	Family

Pfam: PF00001

UniProt features (53 total): helix 12, topological domain 8, transmembrane region 7, sequence conflict 5, strand 4, turn 4, modified residue 3, glycosylation site 3, sequence variant 2, mutagenesis site 2, chain 1, region of interest 1, disulfide bond 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
6K3F	X-RAY DIFFRACTION	2.3
8TII	ELECTRON MICROSCOPY	3
7SK4	ELECTRON MICROSCOPY	3.3
7SK7	ELECTRON MICROSCOPY	3.3
7SK8	ELECTRON MICROSCOPY	3.3
8VJ9	ELECTRON MICROSCOPY	3.3
9E82	ELECTRON MICROSCOPY	3.4
8TIO	ELECTRON MICROSCOPY	3.6
7SK9	ELECTRON MICROSCOPY	3.7
7SK3	ELECTRON MICROSCOPY	3.8
8TIL	ELECTRON MICROSCOPY	3.8
7SK5	ELECTRON MICROSCOPY	4
7SK6	ELECTRON MICROSCOPY	4
8TIN	ELECTRON MICROSCOPY	4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25106-F1	82.47	0.41

Antibody-complex structures (SAbDab): 13 — 7SK3, 7SK4, 7SK5, 7SK6, 7SK7, 7SK8, 7SK9, 8TII, 8TIL, 8TIN, 8TIO, 8VJ9, 9E82

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 (3): 347, 350, 355

Disulfide bonds (1): 117–196

Glycosylation sites (3): 13, 22, 39

Mutagenesis-validated functional residues (2):

Position	Phenotype
145	does not result in cxcl12-inducible chemotaxis, calcium mobilization or erk activation, and has no effect on cxcr7-media
147	does not result in cxcl12-inducible chemotaxis, calcium mobilization or erk activation, and has no effect on cxcr7-media

Function

Pathways and Gene Ontology

Reactome pathways

8 pathways

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

MSigDB gene sets: 354 (showing top): LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_CELL_CHEMOTAXIS, GOBP_RESPONSE_TO_PEPTIDE, GOZGIT_ESR1_TARGETS_DN, GOBP_POSITIVE_REGULATION_OF_MAPK_CASCADE, GOCC_CELL_SURFACE, TGACCTY_ERR1_Q2, SAENZ_DETOX_PATHWAY_AND_CARCINOGENESIS_DN, GOBP_VESICLE_MEDIATED_TRANSPORT, DARWICHE_PAPILLOMA_PROGRESSION_RISK, GOBP_CRANIAL_NERVE_DEVELOPMENT, GOBP_NEGATIVE_REGULATION_OF_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, SENESE_HDAC1_AND_HDAC2_TARGETS_DN, KRASNOSELSKAYA_ILF3_TARGETS_DN

GO Biological Process (17): angiogenesis (GO:0001525), vasculogenesis (GO:0001570), immune response (GO:0006955), cell adhesion (GO:0007155), positive regulation of cytosolic calcium ion concentration (GO:0007204), negative regulation of cell population proliferation (GO:0008285), calcium-mediated signaling (GO:0019722), oculomotor nerve development (GO:0021557), receptor internalization (GO:0031623), cell chemotaxis (GO:0060326), chemokine-mediated signaling pathway (GO:0070098), positive regulation of ERK1 and ERK2 cascade (GO:0070374), negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage (GO:1902230), positive regulation of mesenchymal stem cell migration (GO:1905322), chemotaxis (GO:0006935), signal transduction (GO:0007165), G protein-coupled receptor signaling pathway (GO:0007186)

GO Molecular Function (9): scavenger receptor activity (GO:0005044), coreceptor activity (GO:0015026), C-C chemokine receptor activity (GO:0016493), C-X-C chemokine receptor activity (GO:0016494), C-C chemokine binding (GO:0019957), C-X-C chemokine binding (GO:0019958), G protein-coupled receptor activity (GO:0004930), protein binding (GO:0005515), chemokine binding (GO:0019956)

GO Cellular Component (8): endosome (GO:0005768), early endosome (GO:0005769), plasma membrane (GO:0005886), clathrin-coated pit (GO:0005905), external side of plasma membrane (GO:0009897), cell surface (GO:0009986), recycling endosome (GO:0055037), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-6 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
blood vessel morphogenesis	2
cellular process	2
G protein-coupled receptor signaling pathway	2
chemokine receptor activity	2
chemokine binding	2
endomembrane system	2
endosome	2
membrane	2
cellular anatomical structure	2
anatomical structure formation involved in morphogenesis	1
cell differentiation	1
immune system process	1
response to stimulus	1
regulation of biological quality	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
intracellular signaling cassette	1
cranial nerve development	1
preganglionic parasympathetic fiber development	1
receptor-mediated endocytosis	1
chemotaxis	1
cell migration	1
cellular response to chemical stimulus	1
cytokine-mediated signaling pathway	1
cellular response to chemokine	1
positive regulation of MAPK cascade	1
ERK1 and ERK2 cascade	1
regulation of ERK1 and ERK2 cascade	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
regulation of intrinsic apoptotic signaling pathway in response to DNA damage	1
negative regulation of intrinsic apoptotic signaling pathway	1
positive regulation of cell migration	1
mesenchymal stem cell migration	1
regulation of mesenchymal stem cell migration	1
response to chemical	1
taxis	1
cell communication	1
signaling	1
regulation of cellular process	1

Protein interactions and networks

STRING

1042 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ACKR3	CXCL11	O14625	997
ACKR3	CXCL12	P48061	997
ACKR3	ADM	P35318	871
ACKR3	CXCR4	P30991	850
ACKR3	ARRB2	P32121	848
ACKR3	CCL21	O00585	817
ACKR3	ARRB1	P49407	780
ACKR3	EGFR	P00533	767
ACKR3	CXCL10	P02778	738
ACKR3	MIF	P14174	716
ACKR3	AVPR1A	P37288	669
ACKR3	CXCL9	Q07325	630
ACKR3	SAG	P10523	625
ACKR3	ACKR1	Q16570	622
ACKR3	AP1B1	P78436	620

IntAct

65 interactions, top by confidence:

A	B	Type	Score
ACKR3	CXCR4	psi-mi:“MI:2364”(proximity)	0.850
CXCR4	ACKR3	psi-mi:“MI:2364”(proximity)	0.850
CXCR4	ACKR3	psi-mi:“MI:0915”(physical association)	0.850
CXCR4	ACKR3	psi-mi:“MI:0403”(colocalization)	0.850
ACKR3	ATP5F1B	psi-mi:“MI:0914”(association)	0.640
ACKR3	AVPR1A	psi-mi:“MI:2364”(proximity)	0.570
ACKR3	AVPR1A	psi-mi:“MI:0915”(physical association)	0.570
AVPR1A	ACKR3	psi-mi:“MI:2364”(proximity)	0.570
AVPR1A	ACKR3	psi-mi:“MI:0914”(association)	0.570
ARRB1	ACKR3	psi-mi:“MI:0915”(physical association)	0.460
ACKR3	ARRB1	psi-mi:“MI:0403”(colocalization)	0.460
ACKR3	ADRA1A	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA1B	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA1D	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA2B	psi-mi:“MI:2364”(proximity)	0.420
ACKR3	ADRA2B	psi-mi:“MI:0914”(association)	0.420
ACKR3		psi-mi:“MI:2364”(proximity)	0.410

BioGRID (35): ATP5B (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5D (Affinity Capture-MS), ATP5O (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5O (Affinity Capture-MS), ESPL1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS), MRPL4 (Affinity Capture-MS), UBR7 (Affinity Capture-MS), ACKR3 (Affinity Capture-MS), HECTD2 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS)

ESM2 similar proteins: A1A5S3, A5PLE7, B0UXR0, B5X337, D4A7K7, O00398, O18982, O54689, O97663, P21556, P25105, P25106, P32249, P35351, P35374, P46002, P47749, P47900, P48042, P49650, P49651, P49685, P50052, P51684, P56412, Q1RMI1, Q28929, Q2NNR5, Q3U507, Q3U6B2, Q3UJF0, Q5ZI82, Q61038, Q62035, Q8BZR0, Q8IYL9, Q8K1Z6, Q924T8, Q95N02, Q95N03

Diamond homologs: A0T2N3, F1MV99, O00155, O00590, O08707, O08858, O09027, O35210, O77590, O88410, O89039, O97666, P0C5I1, P0C7U4, P11613, P21109, P25024, P25025, P25095, P25104, P25106, P29089, P29754, P29755, P30555, P30556, P30680, P30874, P30875, P30935, P30936, P30937, P30938, P31391, P32303, P32745, P33396, P33535, P34976, P34993

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
CXCL12	up-regulates	ACKR3	binding
HIC1	“down-regulates quantity by repression”	ACKR3	“transcriptional regulation”
CXCL11	“up-regulates activity”	ACKR3	binding
hsa-miR-101-3p	“down-regulates quantity by repression”	ACKR3	“post transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 26 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
G alpha (s) signalling events	6	20.0×	3e-05
GPCR downstream signalling	5	9.9×	6e-03
Signaling by GPCR	5	9.1×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of cytosolic calcium ion concentration	6	30.5×	4e-06
positive regulation of MAPK cascade	5	17.5×	3e-04
G protein-coupled receptor signaling pathway	10	15.8×	8e-08
cell-cell signaling	5	15.1×	5e-04
protein transport	5	9.5×	4e-03
positive regulation of gene expression	5	8.4×	6e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 1 cancer types — OVT.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	34
Likely pathogenic	0
Uncertain significance	41
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
147967	GRCh38/hg38 2q37.2-37.3(chr2:234835780-242065208)x1	Pathogenic
148764	GRCh38/hg38 2q37.2-37.3(chr2:235757098-239443690)x1	Pathogenic
151026	GRCh38/hg38 2q37.3(chr2:236413722-242126251)x1	Pathogenic
153183	GRCh38/hg38 2q37.2-37.3(chr2:235846916-241841232)x1	Pathogenic
161051	GRCh38/hg38 2q37.1-37.3(chr2:231770279-242126245)x1	Pathogenic
1703651	GRCh37/hg19 2q37.1-37.3(chr2:233227837-242783384)	Pathogenic
1807819	GRCh37/hg19 2q37.2-37.3(chr2:235942616-242783384)x1	Pathogenic
1808622	GRCh37/hg19 2q37.2-37.3(chr2:236878509-242783384)x1	Pathogenic
2685879	GRCh37/hg19 2q36.2-37.3(chr2:225995545-237594511)x3	Pathogenic
3062606	GRCh37/hg19 2q37.2-37.3(chr2:236726690-242783384)x1	Pathogenic
3062615	GRCh37/hg19 2q37.2-37.3(chr2:236057846-242783384)x1	Pathogenic
3247415	NC_000002.11:g.(?237481970)(242801596_?)del	Pathogenic
3362876	Single allele	Pathogenic
34724	GRCh38/hg38 2q37.1-37.3(chr2:231770279-242126245)x1	Pathogenic
395404	GRCh37/hg19 2q37.1-37.3(chr2:233784243-243040217)x1	Pathogenic
4075968	GRCh37/hg19 2q37.2-37.3(chr2:236127397-242783384)x3	Pathogenic
442002	GRCh37/hg19 2q34-37.3(chr2:213518431-242783384)x3	Pathogenic
442425	GRCh37/hg19 2q36.1-37.3(chr2:222077224-239394441)x3	Pathogenic
443370	GRCh37/hg19 2q37.1-37.3(chr2:234495262-242783384)x1	Pathogenic
443896	GRCh37/hg19 2q37.1-37.3(chr2:235539337-242783384)x1	Pathogenic
562671	GRCh37/hg19 2q37.2-37.3(chr2:235790256-242783384)x1	Pathogenic
57420	GRCh38/hg38 2q37.3(chr2:236555233-242126245)x1	Pathogenic
57457	GRCh38/hg38 2q37.1-37.3(chr2:234345842-242126245)x1	Pathogenic
585134	NM_020311.3(ACKR3):c.772G>A (p.Val258Met)	Pathogenic
58847	GRCh38/hg38 2q36.3-37.3(chr2:226978129-236886599)x1	Pathogenic
58852	GRCh38/hg38 2q37.1-37.3(chr2:233453611-242099155)x1	Pathogenic
58879	GRCh38/hg38 2q37.1-37.3(chr2:234172536-242086301)x1	Pathogenic
58880	GRCh38/hg38 2q37.1-37.3(chr2:234668159-242126245)x1	Pathogenic
58882	GRCh38/hg38 2q37.2-37.3(chr2:235268768-242065208)x1	Pathogenic
58883	GRCh38/hg38 2q37.2-37.3(chr2:235741079-242032456)x1	Pathogenic

SpliceAI

468 predictions. Top by Δscore:

Variant	Effect	Δscore
2:236580426:T:A	acceptor_gain	1.0000
2:236580427:G:A	acceptor_gain	0.9900
2:236580437:TA:T	acceptor_loss	0.9900
2:236580438:A:AG	acceptor_gain	0.9900
2:236580438:AG:A	acceptor_gain	0.9900
2:236580438:AGGT:A	acceptor_loss	0.9900
2:236580439:G:C	acceptor_loss	0.9900
2:236580439:G:GA	acceptor_gain	0.9900
2:236580439:GG:G	acceptor_gain	0.9900
2:236580439:GGT:G	acceptor_gain	0.9900
2:236580439:GGTC:G	acceptor_gain	0.9900
2:236580439:GGTCA:G	acceptor_gain	0.9900
2:236580436:ATAG:A	acceptor_gain	0.9800
2:236580437:T:G	acceptor_gain	0.9800
2:236580436:A:AG	acceptor_gain	0.9700
2:236580422:T:TA	acceptor_gain	0.9600
2:236580439:G:T	acceptor_gain	0.9300
2:236569673:TTTAC:T	donor_gain	0.9200
2:236569923:AGG:A	donor_loss	0.9200
2:236569924:GGT:G	donor_loss	0.9200
2:236569925:G:A	donor_loss	0.9200
2:236569926:T:G	donor_loss	0.9200
2:236580434:TCATA:T	acceptor_gain	0.9200
2:236580435:CATAG:C	acceptor_gain	0.9200
2:236580437:TAG:T	acceptor_gain	0.9200
2:236569921:GGAG:G	donor_gain	0.9100
2:236569922:GAGG:G	donor_gain	0.9100
2:236580436:ATAGG:A	acceptor_gain	0.9100
2:236580438:AGGTC:A	acceptor_gain	0.9100
2:236569662:GACTA:G	donor_gain	0.9000

AlphaMissense

2396 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:236580795:G:C	W110C	0.999
2:236580795:G:T	W110C	0.999
2:236580793:T:A	W110R	0.998
2:236580793:T:C	W110R	0.998
2:236580814:T:A	C117S	0.998
2:236580815:G:C	C117S	0.998
2:236580880:A:C	S139R	0.998
2:236580882:C:A	S139R	0.998
2:236580882:C:G	S139R	0.998
2:236580970:T:A	W169R	0.998
2:236580970:T:C	W169R	0.998
2:236581051:T:A	C196S	0.998
2:236581052:G:C	C196S	0.998
2:236581246:T:C	F261L	0.998
2:236581248:C:A	F261L	0.998
2:236581248:C:G	F261L	0.998
2:236581265:C:A	P267H	0.998
2:236580637:G:C	G58R	0.997
2:236580722:T:C	L86P	0.997
2:236580734:A:C	D90A	0.997
2:236580758:C:G	P98R	0.997
2:236580815:G:A	C117Y	0.997
2:236580816:C:G	C117W	0.997
2:236580856:A:C	S131R	0.997
2:236580858:C:A	S131R	0.997
2:236580858:C:G	S131R	0.997
2:236581126:T:C	F221L	0.997
2:236581128:T:A	F221L	0.997
2:236581128:T:G	F221L	0.997
2:236581136:C:A	P224H	0.997

dbSNP variants (sampled 300 via entrez): RS1000003998 (2:236575003 A>G), RS1000097995 (2:236543654 A>G), RS1000104140 (2:236547585 G>A), RS1000258195 (2:236580389 A>T), RS1000266710 (2:236563634 GATTA>G), RS1000336462 (2:236569315 T>C), RS1000430473 (2:236575101 C>G,T), RS1000458933 (2:236556880 G>C,T), RS1000476076 (2:236547894 G>A), RS1000661091 (2:236571248 A>G), RS1000796495 (2:236538166 T>A), RS1000877289 (2:236540769 G>A,C,T), RS1000899112 (2:236552755 G>A,T), RS1000977455 (2:236557149 T>C), RS1001004910 (2:236573658 GTTATC>G)

Disease associations

OMIM: gene MIM:610376 | disease phenotypes: MIM:600430, MIM:158810, MIM:192500, MIM:619215

GenCC curated gene-disease

Disease	Classification	Inheritance
oculomotor-abducens synkinesis	Moderate	Autosomal recessive

Mondo (5): 2q37 microdeletion syndrome (MONDO:0010886), Bethlem myopathy 1A (MONDO:0024530), familial long QT syndrome (MONDO:0019171), oculomotor-abducens synkinesis (MONDO:0030976), primary ovarian failure (MONDO:0005387)

Orphanet (5): 2q37 microdeletion syndrome (Orphanet:1001), Bethlem muscular dystrophy (Orphanet:610), Romano-Ward syndrome (Orphanet:101016), Congenital long QT syndrome (Orphanet:768), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000508	Ptosis
HP:0003577	Congenital onset
HP:0009921	Duane anomaly
HP:0033851	Oculomotor synkinesis

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001621_8	Airflow obstruction	3.000000e-06
GCST004996_1	Total mean fractional anisotropy measurement in first episode schizophrenia	4.000000e-08
GCST005359_4	Disease progression in age-related macular degeneration	6.000000e-08
GCST006427_19	Depression in smokers	3.000000e-06
GCST006979_94	Heel bone mineral density	4.000000e-10
GCST010698_12	Subcortical volume (min-P)	7.000000e-09
GCST010699_31	Brain morphology (min-P)	5.000000e-09
GCST010701_33	Cortical surface area (MOSTest)	5.000000e-28
GCST010702_97	Subcortical volume (MOSTest)	2.000000e-08
GCST010703_318	Brain morphology (MOSTest)	8.000000e-22

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0003892	pulmonary function measurement
EFO:0005674	white matter microstructure measurement
EFO:0008399	mean fractional anisotropy measurement
EFO:0008336	disease progression measurement
EFO:0009270	heel bone mineral density
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750
C538317	Chromosome 2q37 deletion syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2010631 (SINGLE PROTEIN)

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 (7 total), top 7:

Ligand	Action	Affinity	Parameter
LIH383	Antagonist	9.21	pEC50
α-CGRP	Agonist	8.52	pEC50
canverixin	Antagonist	8.49	pIC50
CXCL12α	Agonist	7.9	pEC50
adrenomedullin	Agonist	7.0	pEC50
plerixafor	Agonist	6.85	pEC50
TC14012	Agonist	6.46	pEC50

Binding affinities (BindingDB)

614 measured of 715 human assays (715 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[(5-benzamido-2-chlorophenyl)methyl]-N-cyclopentylpiperidine-4-carboxamide	EC50	0.4 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[4-chloro-3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-fluoropyridine-2-carboxamide	EC50	0.4 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[(4-fluorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxamide	EC50	0.5 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-(trifluoromethyl)pyridine-2-carboxamide	EC50	0.5 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-chloropyridine-2-carboxamide	EC50	0.6 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-6-(trifluoromethyl)pyridine-2-carboxamide	EC50	0.6 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-(trifluoromethyl)pyridine-2-carboxamide	EC50	0.6 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
5-chloro-N-[4-chloro-3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-3-carboxamide	EC50	0.6 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-fluoropyridine-2-carboxamide	EC50	0.6 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-chloro-3-fluoropyridine-2-carboxamide	EC50	0.7 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
5-chloro-N-[3-[[4-(2-methylbutan-2-ylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	0.8 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-fluoropyridine-2-carboxamide	EC50	0.8 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-fluoropyridine-2-carboxamide	EC50	0.8 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[4-chloro-3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-(trifluoromethyl)pyridine-3-carboxamide	EC50	0.8 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N-propan-2-ylpiperidine-4-carboxamide	EC50	0.8 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N-cyclopentylpiperidine-4-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
6-bromo-N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]-6-methylpyridine-2-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-cyclopentyl-1-[[3-[(4-fluorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
1-[[2-chloro-5-[(4-fluorobenzoyl)amino]phenyl]methyl]-N-cyclopentylpiperidine-4-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]quinoline-2-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[(2,2,3,3-tetramethylcyclopropanecarbonyl)amino]phenyl]methyl]piperidine-4-carboxamide	EC50	0.9 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]-6-(trifluoromethyl)pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[[2-(4-chlorophenyl)-2-methylpropanoyl]amino]phenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
1-[[3-(bicyclo[4.2.0]octa-1,3,5-triene-7-carbonylamino)phenyl]methyl]-N-tert-butylpiperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]-3-methylpyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]-4-methylphenyl]-6-(trifluoromethyl)pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[5-[(4-fluorobenzoyl)amino]-2-methylphenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[(1-phenylcyclopropanecarbonyl)amino]phenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[(2-methyl-2-phenylpropanoyl)amino]phenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(propylcarbamoyl)piperidin-1-yl]methyl]phenyl]-6-(trifluoromethyl)pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(2-methylbutan-2-ylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-(trifluoromethyl)pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
5-chloro-3-fluoro-N-[3-[[4-(2-methylbutan-2-ylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-1-oxido-6-(trifluoromethyl)pyridin-1-ium-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(2-methylbutan-2-ylcarbamoyl)piperidin-1-yl]methyl]phenyl]-1-oxido-6-(trifluoromethyl)pyridin-1-ium-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
6-chloro-N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
3-bromo-N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
5-chloro-N-[3-[[4-(cyclohexylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
5-chloro-N-[3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]pyridine-3-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[4-chloro-3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-(trifluoromethyl)pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[4-chloro-3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]quinoline-6-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N-cyclobutylpiperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
1-[[3-[(4-chlorobenzoyl)amino]phenyl]methyl]-N,N-diethylpiperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(cyclopentylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-fluoro-1-oxidopyridin-1-ium-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-6-(trifluoromethyl)pyridine-2-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-[3-[[4-(tert-butylcarbamoyl)piperidin-1-yl]methyl]phenyl]-5-(trifluoromethyl)pyridine-3-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[[2-(2,6-dichlorophenyl)acetyl]amino]phenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives
N-tert-butyl-1-[[3-[[2-(2-chlorophenyl)acetyl]amino]phenyl]methyl]piperidine-4-carboxamide	EC50	1 nM	US-9428456: 1-[m-carboxamido(hetero)aryl-methyl]-heterocyclyl-carboxamide derivatives

ChEMBL bioactivities

1629 potent at pChembl≥5 of 1666 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	IC50	0.3	nM	CHEMBL6045306
9.52	IC50	0.3	nM	CHEMBL5766130
9.43	IC50	0.37	nM	CHEMBL4758472
9.40	EC50	0.4	nM	CHEMBL3900132
9.40	EC50	0.4	nM	CHEMBL3890099
9.30	EC50	0.5	nM	CHEMBL3920616
9.30	EC50	0.5	nM	CHEMBL3962511
9.28	Ki	0.53	nM	CHEMBL4782111
9.22	EC50	0.6	nM	CHEMBL3889555
9.22	EC50	0.6	nM	CHEMBL3901386
9.22	EC50	0.6	nM	CHEMBL3905861
9.22	EC50	0.6	nM	CHEMBL3981643
9.22	EC50	0.6	nM	CHEMBL3922943
9.22	IC50	0.6	nM	CHEMBL4799528
9.21	EC50	0.61	nM	CHEMBL5194677
9.15	EC50	0.7	nM	CHEMBL3954299
9.12	IC50	0.75	nM	CHEMBL4794973
9.10	EC50	0.8	nM	CHEMBL3981109
9.10	EC50	0.8	nM	CHEMBL3975981
9.10	EC50	0.8	nM	CHEMBL3969034
9.10	EC50	0.8	nM	CHEMBL3973619
9.10	EC50	0.8	nM	CHEMBL3944155
9.06	IC50	0.864	nM	CHEMBL4782111
9.05	EC50	0.9	nM	CHEMBL3960767
9.05	EC50	0.9	nM	CHEMBL3912143
9.05	EC50	0.9	nM	CHEMBL3963616
9.05	EC50	0.9	nM	CHEMBL3954443
9.05	EC50	0.9	nM	CHEMBL3945184
9.05	EC50	0.9	nM	CHEMBL3911787
9.05	EC50	0.9	nM	CHEMBL3920333
9.05	IC50	0.9	nM	CHEMBL4782111
9.04	IC50	0.903	nM	CHEMBL4782111
9.02	IC50	0.962	nM	CHEMBL4782111
9.01	IC50	0.989	nM	CHEMBL4782111
9.01	IC50	0.985	nM	CHEMBL4782111
9.00	EC50	1	nM	CHEMBL2013231
9.00	EC50	1	nM	CHEMBL3945376
9.00	EC50	1	nM	CHEMBL3916030
9.00	EC50	1	nM	CHEMBL3907074
9.00	EC50	1	nM	CHEMBL3978168
9.00	EC50	1	nM	CHEMBL3959846
9.00	EC50	1	nM	CHEMBL3949324
9.00	EC50	1	nM	CHEMBL3939471
9.00	EC50	1	nM	CHEMBL3941353
9.00	EC50	1	nM	CHEMBL3904650
9.00	EC50	1	nM	CHEMBL3891245
9.00	EC50	1	nM	CHEMBL3979681
9.00	EC50	1	nM	CHEMBL3974085
9.00	EC50	1	nM	CHEMBL3933763
9.00	EC50	1	nM	CHEMBL3982018

PubChem BioAssay actives

464 with measured affinity, of 716 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-[(3S,4S)-1-cyclohexyl-3-(2-pyridin-2-ylpropan-2-ylcarbamoyl)piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0004	uM
N-[(3S,4S)-1-(cyclopropylmethyl)-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701550: Binding affinity to SNAP-tag fused human CXCR7 expressed in HEK293 cells by HTRF assay	ki	0.0005	uM
N-[(3S,4S)-1-(cyclobutylmethyl)-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0006	uM
(2S)-6-amino-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[2-[[2-[[(2S)-2-amino-3-phenylpropanoyl]amino]acetyl]amino]acetyl]amino]-3-phenylpropanoyl]amino]-4-methylsulfanylbutanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]-5-(diaminomethylideneamino)pentanoyl]amino]hexanamide	1852188: Agonist activity at human C-terminal Smbit-tagged ACKR3 assessed as beta-arrestin recruitment by Nanoluciferase complementation-based assay	ec50	0.0006	uM
N-[(3S,4S)-1-cyclohexyl-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0008	uM
N-[(E)-3-(2-fluorophenyl)-2-methylprop-2-enyl]-3,4-dimethoxy-N-[2-(1-methylpyrrolidin-2-yl)ethyl]benzamide	654455: Agonist activity at human CXCR7 expressed in HEK293T cells co-expressing beta-arrestin2-YFP assessed as beta-arrestin2 recruitment after 1 hr by BRET assay	ec50	0.0010	uM
N-[(3R,4R)-1-cyclohexyl-3-(dimethylcarbamoyl)piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0015	uM
N-[(3S,4S)-1-cyclohexyl-3-(dimethylcarbamoyl)piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0015	uM
N-[(E)-3-(2-fluorophenyl)-2-methylprop-2-enyl]-3,4,5-trimethoxy-N-[2-(1-methylpyrrolidin-2-yl)ethyl]benzamide	654455: Agonist activity at human CXCR7 expressed in HEK293T cells co-expressing beta-arrestin2-YFP assessed as beta-arrestin2 recruitment after 1 hr by BRET assay	ec50	0.0016	uM
N-[(3S,4S)-1-cyclopentyl-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0019	uM
methyl (3S,4S)-1-cyclohexyl-4-[[5-(2,4-difluorophenyl)-1,2-oxazole-3-carbonyl]amino]piperidine-3-carboxylate	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0020	uM
N-[(3S,4S)-1-cyclohexyl-3-methoxypiperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0020	uM
N-[(3S,4S)-1-cyclohexyl-3-hydroxypiperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0020	uM
5-(2,4-difluorophenyl)-N-[(3S,4S)-1-[(1-methylcyclopropyl)methyl]-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0027	uM
N-[(3S,4S)-1-cyclohexyl-3-(2-phenylethylcarbamoyl)piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0027	uM
N-[(3S,4S)-1-cyclohexyl-3-[[(1R)-1-pyridin-2-ylethyl]carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0032	uM
N-[(3S,4S)-1-cyclohexyl-3-[(1-pyridin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0042	uM
2-[3-[(3S,6S,9R,12S,18R)-9-benzyl-16-[3-(2-chlorophenyl)propyl]-6,12-bis(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosan-3-yl]propyl]guanidine	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0050	uM
N-[(3S,4S)-1-cyclohexyl-3-(hydroxymethyl)piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0050	uM
N-[(3S,4S)-1-cyclohexyl-3-ethoxypiperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0050	uM
N-(1-cyclohexylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0050	uM
N-[(E)-3-(2-fluorophenyl)-2-methylprop-2-enyl]-3,4,5-trimethoxy-N-[2-[(2R)-1-methylpyrrolidin-2-yl]ethyl]benzamide	2005801: Binding affinity to ACKR3 (unknown origin) by [125I] CXCL12 displacement assay	ec50	0.0050	uM
N-[(3S,4S)-1-cyclohexyl-3-[[(1R)-1-phenylethyl]carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0055	uM
[4-[[4-(7-ethylimidazo[1,2-a]pyridin-8-yl)-1,4-diazepan-1-yl]methyl]piperidin-1-yl]-[(1R,2S,4S)-7-oxabicyclo[2.2.1]heptan-2-yl]methanone	1480308: Modulation of prolink-tagged human CXCR7 expressed in CHO-K1 cells assessed as induction of beta-arrestin recruitment after 30 mins by beta-galactosidase reporter assay	ec50	0.0070	uM
N-(1-cyclohexylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,3,4-oxadiazole-2-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0070	uM
2-[3-[(3S,6S,9R,12S,18R)-9-benzyl-16-[3-(2,4-difluorophenyl)propyl]-6,12-bis(1H-indol-3-ylmethyl)-2,5,8,11,14,17-hexaoxo-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosan-3-yl]propyl]guanidine	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0079	uM
(3S,6S,9R,12S,18R)-9-benzyl-6-(2,2-dimethylpropyl)-12,16-bis(3-phenylpropyl)-3-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosane-2,5,8,11,14,17-hexone	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0079	uM
4-[[4-(7-methoxyquinolin-8-yl)-1,4-diazepan-1-yl]methyl]-2-phenyl-1,3-thiazole	1480307: Displacement of [125I]CXCL12 from human CXCR7 expressed in CHO-K1 cell membranes after 2 hrs by scintillation counting method	ki	0.0079	uM
2-hydroxy-N,N-dimethyl-3-[[2-[[(5-methylfuran-2-yl)-(2-methyloxolan-2-yl)methyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide	1953247: Antagonist activity at CXCR7 (unknown origin)	ic50	0.0079	uM
N-[(3S,4S)-1-cyclohexyl-3-(2-pyridin-2-ylethylcarbamoyl)piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0087	uM
(3S,6S,9R,12S,18R)-9-benzyl-16-[3-(2,4-difluorophenyl)propyl]-6-(2,2-dimethylpropyl)-12-(phenylmethoxymethyl)-3-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosane-2,5,8,11,14,17-hexone	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0090	uM
N-(1-cyclobutylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0090	uM
N-(1-cyclopentylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0090	uM
N-[(3S,4S)-1-cyclohexyl-3-[methyl(2-phenylethyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0100	uM
(3S)-3-[4-(7-ethylimidazo[1,2-a]pyridin-8-yl)-1,4-diazepan-1-yl]-3-[1-[(1R,2S,4S)-7-oxabicyclo[2.2.1]heptane-2-carbonyl]piperidin-4-yl]propanamide	1480308: Modulation of prolink-tagged human CXCR7 expressed in CHO-K1 cells assessed as induction of beta-arrestin recruitment after 30 mins by beta-galactosidase reporter assay	ec50	0.0110	uM
3,4,5-trimethoxy-N-[2-(1-methylpyrrolidin-2-yl)ethyl]-N-[(E)-3-phenylbut-2-enyl]benzamide	654454: Displacement of [125I]-CXCL12 from human CXCR7 expressed in HEK293 cells after 3 hrs	ki	0.0126	uM
3-[2-[6-[3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)propanoylamino]hexanoylamino]ethoxy]-N-[(E)-3-(2-fluorophenyl)-2-methylprop-2-enyl]-4,5-dimethoxy-N-[2-[(2R)-1-methylpyrrolidin-2-yl]ethyl]benzamide	2005803: Binding affinity to NanoLuc tagged human wild type ACKR3 expressed in HEK293G cells using furimazine as NanoLuc substrate preincubated for 1 hr in dark in presence of (R)-N-(3-(2-fluorophenyl)-2methylallyl)-3,4,5-trimethoxyN-(2-(1-methylpyrrolidin-2yl)ethyl)benzamide followed by substrate addition and measured after 5 mins by NanoBRET assay	kd	0.0129	uM
3,4,5-trimethoxy-N-[(E)-2-methyl-3-phenylprop-2-enyl]-N-[2-(1-methylpyrrolidin-2-yl)ethyl]benzamide	654454: Displacement of [125I]-CXCL12 from human CXCR7 expressed in HEK293 cells after 3 hrs	ki	0.0158	uM
(1R,5S)-3-N-ethyl-3-N-methyl-6-N-[(3S)-1-(1,7-naphthyridin-8-yl)pyrrolidin-3-yl]-3-azabicyclo[3.1.0]hexane-3,6-dicarboxamide	1752250: Binding affinity to CXCR7 (unknown origin) assessed as inhibition constant	ki	0.0170	uM
5-(2,4-difluorophenyl)-N-[(3S,4S)-1-propyl-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0184	uM
(3S,6S,9R,12S,18R)-9-benzyl-7-methyl-12,16-bis(3-phenylpropyl)-3-(pyridin-3-ylmethyl)-6-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosane-2,5,8,11,14,17-hexone	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0199	uM
N-[(E)-3-(2-fluorophenyl)-2-methylprop-2-enyl]-3,4,5-trimethoxy-N-[2-[(2S)-1-methylpyrrolidin-2-yl]ethyl]benzamide	2005801: Binding affinity to ACKR3 (unknown origin) by [125I] CXCL12 displacement assay	ec50	0.0199	uM
N-(1-cyclohexylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,2,4-oxadiazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0200	uM
5-(2,4-difluorophenyl)-N-[(3S,4S)-1-propan-2-yl-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0205	uM
N-(1-benzylpiperidin-4-yl)-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701533: Antagonist activity at CXCR7 (unknown origin) expressed in CHO-K1 cells co-expressing beta-arrestin assessed as reduction in compound-1 induced response pre-incubated for 15 mins before compound-1 addition	ic50	0.0210	uM
(3S,6S,9R,12S,18R)-9-benzyl-6-(1H-indol-3-ylmethyl)-12,16-bis(3-phenylpropyl)-3-(pyridin-3-ylmethyl)-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosane-2,5,8,11,14,17-hexone	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0230	uM
(3S,6S,9R,12S,18R)-9-benzyl-12,16-bis(3-phenylpropyl)-3-(pyridin-3-ylmethyl)-6-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosane-2,5,8,11,14,17-hexone	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0240	uM
5-(2,4-difluorophenyl)-N-[(3S,4S)-1-[(1-fluorocyclopropyl)methyl]-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0240	uM
(3S,6S,9R,12S,18R)-9,12-dibenzyl-16-[3-(2,4-difluorophenyl)propyl]-6-(2,2-dimethylpropyl)-3-(1,3-thiazol-4-ylmethyl)-1,4,7,10,13,16-hexazabicyclo[16.3.0]henicosane-2,5,8,11,14,17-hexone	1476744: Displacement of [125I]-CXCL12 from human CXCR7 expressed in CHOK1 cell membranes after 2 hrs by scintillation counting method	ki	0.0250	uM
N-[(3S,4S)-1-cyclobutyl-3-[(1-pyrimidin-2-ylcyclopropyl)carbamoyl]piperidin-4-yl]-5-(2,4-difluorophenyl)-1,2-oxazole-3-carboxamide	1701534: Antagonist activity at CXCR7 (unknown origin) expressed in human U2OS cells co-expressing beta-arrestin assessed as reduction in CXCL12-alpha induced response pre-incubated for 15 mins before CXCL12-alpha addition and measured after 24 hrs	ic50	0.0250	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression, increases methylation	6
Estradiol	affects cotreatment, increases expression, decreases expression	5
Valproic Acid	increases expression, affects cotreatment	5
trichostatin A	affects cotreatment, increases expression	3
Lipopolysaccharides	decreases reaction, affects expression, increases expression, affects reaction	3
Cadmium Chloride	increases expression, decreases expression, increases abundance	3
bisphenol A	decreases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	affects expression, increases methylation, affects cotreatment	2
Calcitriol	affects cotreatment, decreases expression	2
Formaldehyde	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	decreases expression, increases expression	2
Tamoxifen	affects expression, affects cotreatment, decreases expression	2
Tobacco Smoke Pollution	decreases expression, increases expression	2
Cyclosporine	decreases expression, increases expression	2
Raloxifene Hydrochloride	affects expression, affects cotreatment, decreases expression	2
Particulate Matter	decreases expression, increases abundance	2
GSK-J4	decreases expression	1
bisphenol F	affects cotreatment, decreases methylation	1
22-hydroxycholesterol	increases expression	1
triphenyl phosphate	affects expression	1
2,5,2’,5’-tetrachlorobiphenyl	increases expression	1
arsenite	affects expression	1
afimoxifene	decreases expression, decreases reaction	1
cobaltous chloride	increases expression	1
nickel chloride	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases expression	1
chloroquine diphosphate	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, decreases expression	1

ChEMBL screening assays

102 unique, capped per target: 77 binding, 24 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2013880	Binding	Displacement of [125I]-CXCL12 from human CXCR7 expressed in HEK293 cells after 3 hrs	Synthesis, modeling and functional activity of substituted styrene-amides as small-molecule CXCR7 agonists. — Eur J Med Chem
CHEMBL2013881	Functional	Agonist activity at human CXCR7 expressed in HEK293T cells co-expressing beta-arrestin2-YFP assessed as beta-arrestin2 recruitment after 1 hr by BRET assay	Synthesis, modeling and functional activity of substituted styrene-amides as small-molecule CXCR7 agonists. — Eur J Med Chem
CHEMBL4406565	ADMET	Agonist activity at human PK1-tgged CXCR7 expressed in CHOK1 cells assessed as induction of beta-arrestin recruitment at 10 uM measured after 90 mins by beta-galactosidase based PathHunter assay	Discovery, Optimization, and Characterization of ML417: A Novel and Highly Selective D3 Dopamine Receptor Agonist. — J Med Chem

Cellosaurus cell lines

10 cell lines: 6 cancer cell line, 3 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A7BP	NP-2/CD4/RDC1	Cancer cell line	Male
CVCL_B8AS	Abcam HCT 116 ACKR3 KO	Cancer cell line	Male
CVCL_B8S3	Abcam MCF-7 ACKR3 KO	Cancer cell line	Female
CVCL_B9CU	Abcam A-549 ACKR3 KO	Cancer cell line	Male
CVCL_E6AL	CHO-CXCR7-Low	Spontaneously immortalized cell line	Female
CVCL_E6AM	CHO-CXCR7-Medium-High	Spontaneously immortalized cell line	Female
CVCL_E6AN	HEK293-CXCR7	Transformed cell line	Female
CVCL_KW82	PathHunter CHO-K1 CXCR7 beta-arrestin	Spontaneously immortalized cell line	Female
CVCL_LA18	PathHunter U2OS CXCR7 Activated GPCR Internalization	Cancer cell line	Female
CVCL_ZK14	Tango CXCR7-bla U2OS	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT01238250	Not specified	RECRUITING	Online Study of People Who Have Genetic Changes and Features of Autism: Simons Searchlight
NCT04020159	Not specified	UNKNOWN	Global Registry for COL6-related Dystrophies
NCT05906732	PHASE1/PHASE2	TERMINATED	Study of LQT-1213 on QTc-induced Prolongation in Healthy Adult Subjects (Part1) and on Congenital Long QT in Patients Diagnosed With Type 2 or 3 Long QT Syndrome (Part 2).
NCT00005176	Not specified	COMPLETED	Long QT Syndrome-Population Genetics and Cardiac Studies
NCT00005250	Not specified	COMPLETED	Linkage Study of Long QT Syndrome In An Amish Kindred
NCT00005367	Not specified	COMPLETED	Epidemiology of Long QTand Asian Sudden Death in Sleep
NCT00221832	Not specified	UNKNOWN	Molecular Genetic Screening and Identification of Congenital Arrhythmogenic Diseases
NCT00292032	Not specified	COMPLETED	Registry of Unexplained Cardiac Arrest
NCT00335036	Not specified	TERMINATED	Pediatric Lead Extractability and Survival Evaluation (PLEASE)