NECTIN4

Summary

NECTIN4 (nectin cell adhesion molecule 4, HGNC:19688) is a protein-coding gene on chromosome 1q23.3, encoding Nectin-4 (Q96NY8). Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1.

This gene encodes a member of the nectin family. The encoded protein contains two immunoglobulin-like (Ig-like) C2-type domains and one Ig-like V-type domain. It is involved in cell adhesion through trans-homophilic and -heterophilic interactions. It is a single-pass type I membrane protein. The soluble form is produced by proteolytic cleavage at the cell surface by the metalloproteinase ADAM17/TACE. The secreted form is found in both breast tumor cell lines and breast tumor patients. Mutations in this gene are the cause of ectodermal dysplasia-syndactyly syndrome type 1, an autosomal recessive disorder. Alternatively spliced transcript variants have been found but the full-length nature of the variant has not been determined.

Source: NCBI Gene 81607 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia-syndactyly syndrome 1 (Definitive, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 93 total — 10 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_030916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19688
Approved symbol	NECTIN4
Name	nectin cell adhesion molecule 4
Location	1q23.3
Locus type	gene with protein product
Status	Approved
Aliases	nectin-4, PRR4, LNIR
Ensembl gene	ENSG00000143217
Ensembl biotype	protein_coding
OMIM	609607
Entrez	81607

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000368012, ENST00000486694, ENST00000891630, ENST00000968999

RefSeq mRNA: 1 — MANE Select: NM_030916 NM_030916

CCDS: CCDS1216

Canonical transcript exons

ENST00000368012 — 9 exons

Exon	Start	End
ENSE00001040996	161074217	161074373
ENSE00001040998	161073225	161073299
ENSE00001041003	161074611	161074759
ENSE00001446125	161070998	161072885
ENSE00001446126	161089218	161089558
ENSE00002232577	161076355	161076475
ENSE00003348696	161079590	161079949
ENSE00003351283	161077453	161077743
ENSE00003657274	161073720	161073795

Expression profiles

Bgee: expression breadth ubiquitous, 160 present calls, max score 97.60.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8456 / max 167.6281, expressed in 479 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
15583	1.9973	305
15580	0.5751	165
15582	0.1284	68
15584	0.1029	56
15585	0.0304	15
15581	0.0115	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower esophagus mucosa	UBERON:0035834	97.60	gold quality
skin of abdomen	UBERON:0001416	97.27	gold quality
skin of leg	UBERON:0001511	96.92	gold quality
esophagus mucosa	UBERON:0002469	96.04	gold quality
zone of skin	UBERON:0000014	94.83	gold quality
minor salivary gland	UBERON:0001830	90.88	gold quality
mouth mucosa	UBERON:0003729	90.41	gold quality
upper arm skin	UBERON:0004263	89.56	gold quality
gingiva	UBERON:0001828	87.82	gold quality
gingival epithelium	UBERON:0001949	87.81	gold quality
saliva-secreting gland	UBERON:0001044	87.12	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.75	gold quality
esophagus squamous epithelium	UBERON:0006920	86.18	gold quality
amniotic fluid	UBERON:0000173	85.93	gold quality
nasal cavity epithelium	UBERON:0005384	85.57	silver quality
vagina	UBERON:0000996	84.52	gold quality
upper leg skin	UBERON:0004262	84.24	gold quality
islet of Langerhans	UBERON:0000006	83.08	gold quality
oral cavity	UBERON:0000167	82.09	gold quality
tonsil	UBERON:0002372	81.08	gold quality
buccal mucosa cell	CL:0002336	79.93	silver quality
placenta	UBERON:0001987	78.96	gold quality
mammalian vulva	UBERON:0000997	78.43	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	77.89	gold quality
nasal cavity mucosa	UBERON:0001826	77.78	gold quality
palpebral conjunctiva	UBERON:0001812	77.53	gold quality
pharyngeal mucosa	UBERON:0000355	77.14	gold quality
nipple	UBERON:0002030	76.40	gold quality
pancreatic ductal cell	CL:0002079	76.29	silver quality
pancreas	UBERON:0001264	75.41	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 8.

Experiment	Marker?	Max mean expression
E-ENAD-21	yes	951.99
E-CURD-7	yes	910.39
E-MTAB-8142	yes	476.23
E-CURD-114	yes	75.50
E-MTAB-6701	yes	45.75
E-HCAD-10	yes	15.31
E-MTAB-6678	yes	6.54
E-MTAB-10596	no	146.24
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

59 targeting NECTIN4, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-4267	99.96	66.53	2368
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-6715B-5P	99.64	69.63	1420
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-3942-3P	99.57	69.03	2854
HSA-MIR-4269	99.55	69.89	1373
HSA-MIR-4251	99.40	69.19	3363

Literature-anchored findings (GeneRIF, showing 40)

• the active form of TACE is overexpressed in breast tumors and may indicate that TACE is responsible for Nectin-4 shedding not only in vitro but also in vivo (PMID:15784625)
• Nectin-4 was not detected in normal breast epithelium; by contrast Nectin-4 was expressed in ductal breast carcinoma. (PMID:17474988)
• Nectin-4 might play a significant role in lung carcinogenesis, and it should be a new candidate serum and tissue biomarker, as well as a therapeutic target. (PMID:19679554)
• Ectodermal dysplasia-syndactyly syndrome is the second known “nectinopathy” caused by mutations in a nectin adhesion molecule. (PMID:20691405)
• nectin 4 may serve as a potential biomarker that helps discriminate benign gynecologic diseases from ovarian cancer in a panel with CA125. (PMID:20959669)
• Ectoderma dysplasia-syndactyly syndrome. Second example of “nectinopathy”. (PMID:21333831)
• Sequence analysis revealed a homozygous missense mutation (c.635C>G; p.Pro212Arg) in the recently reported PVRL4 gene causing EDSS1 (PMID:21346770)
• The findings of study suggest that increased expression of Nectin-4 may indicate a worse prognosis in breast cancer patients. (PMID:21526486)
• Measles virus infection reduced PVRL4 surface expression in MCF7 cells, a property that is characteristic of receptor-associated viral infections. (PMID:21901103)
• measles virus targets nectin-4 to emerge in the airways (PMID:22048310)
• crystals of nectin-4 diffracted to 1.8 A resolution and belonged to space group P2(1), with unit-cell parameters a = 33.1, b = 51.7, c = 56.9 A, beta = 94.7 degrees (PMID:22869128)
• Data suggest that expression of nectin-4 is up-regulated in eutopic endometrium of patients with endometriosis compared with control subjects. (PMID:22926846)
• We show that human nectin4 is fully functional as a canince distemper virus receptor. (PMID:23174504)
• structure of the membrane-distal domain of nectin-4 in complex with measles virus hemagglutinin (MV-H; structure shows nectin-4 binds the MV-H beta4-beta5 groove exclusively via its N-terminal IgV domain; the contact interface is dominated by hydrophobic interactions (PMID:23202587)
• Transformation of breast cancer cells is dependent on PVRL4. (PMID:23682311)
• Thus, while nectin-4 and CD46 interact functionally with the measles virus H protein beta4-beta5 hydrophobic groove, SLAM merely covers it. (PMID:23760251)
• Ablation of nectin4 binding compromises CD46 usage by a hybrid vesicular stomatitis virus/measles virus. (PMID:24335299)
• data outline a synergistic action of nectin-1 and -4 in the early steps of AJ formation and implicate this interaction in modulating the Rac1 signaling pathway (PMID:24577405)
• Ovarian tissue expression and serum nectin 4 appear to be potential markers in ovarian cancer. (PMID:25019423)
• Authors show that the same key residues in the BC and FG loops of nectin-4 govern binding to the measles virus attachment protein hemagglutinin (H) and cell entry, nectin-4 homodimerization, and heterodimerization with nectin-1. (PMID:25275122)
• The present study described clinical investigation of the EDSS1 identified in a large consanguineous family; DNA sequence analysis revealed a novel homozygous nonsense mutation (181C>T, p.Asp61*) in the PVRL4 gene. (PMID:25529316)
• Nectin-4 is a significant prognostic predictor, and may play a critical role in pancreatic cancer. Nectin-4 may be novel therapeutic target for pancreatic cancer. (PMID:25888293)
• In airway epithelial cells, measles virus spread requires the nectin-4/afadin complex and is based on cytoplasm transfer between columnar cells. (PMID:25926640)
• The data presented in this study suggested that nectin-4 may be a therapeutic target for systemic lupus erythematous through affecting the cell apoptosis (PMID:26617807)
• Nectin-4 is critical for gallbladder cancer cell progression via PI3K/AKT pathway activation of Rac1. (PMID:26949052)
• High Nectin-4 expression is associated with neoplasms. (PMID:27013195)
• Nectin-4 expression, when compared with control group, was higher in endometriotic lesions of patients having ovarian endometriosis and peritoneal endometriosis. This difference was significant in the endometrium of patients having endometriosis. (PMID:27328518)
• This study suggests that PVRL4 is post-transcriptionally regulated by miR-128 and miR-31. (PMID:27507538)
• Nectin-4 is both a new promising prognostic biomarker and specific therapeutic target for Triple-negative breast cancers (PMID:27998973)
• Nectin-4 promotes cell-cell adhesion/aggregation, migration, and proliferation of ovarian tumor cells. (PMID:28038455)
• ADAM17 and ADAM10 cleave Nectin-4 and release soluble Nectin-4 (sN4). (PMID:28232483)
• We show that Measles virus gains entry into MCF7, DLD-1, and HTB-20 cancer cells through a PVRL4-mediated macropinocytosis pathway and identified the typical cellular GTPase and kinase involved. (PMID:28250131)
• nectin-4 serves as a stimulatory co-receptor for the prolactin receptor by regulating the feedback inhibition of SOCS1 in the JAK2-STAT5a signaling pathway (PMID:28258213)
• Nectin-4 is not only a BCSC marker but also a breast cancer metastasis marker (PMID:28600142)
• We suggest that Nectin-4 is a relevant prognostic factor and a therapeutic target in luminalB (HER2 negative) breast cancer. (PMID:28778498)
• that Nectin-4 had a promoter effect on human gastric cancer cell growth and motility (PMID:29208564)
• novel homozygous missense variant in NECTIN4 causing ectodermal dysplasia cutaneous syndactyly syndrome in a consanguineous Pakistani family (PMID:29430627)
• soluble nectin-4 ecto-domain promotes breast cancer induced angiogenesis via endothelial Integrin-beta4 (PMID:30056265)
• There are as yet unknown factors that induce NECTIN4 overexpression in trophoblast cells that may contribute to abnormal placentation via an aberrant immune response and the onset of a preeclamptic pregnancy. (PMID:30217189)
• Nectin-1-expressing cells acquire dye-labeled cytoplasmic proteins synchronously with nectin-4, a process most active during cell adhesion. (PMID:31331966)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	nectin4a	ENSDARG00000077419
danio_rerio	nectin4b	ENSDARG00000103148
mus_musculus	Nectin4	ENSMUSG00000006411
rattus_norvegicus	Nectin4	ENSRNOG00000004029
drosophila_melanogaster	Fas3	FBGN0000636

Paralogs (14): PVR (ENSG00000073008), CD200 (ENSG00000091972), CADM4 (ENSG00000105767), CRTAM (ENSG00000109943), NECTIN1 (ENSG00000110400), NECTIN2 (ENSG00000130202), CD226 (ENSG00000150637), CADM3 (ENSG00000162706), SMAGP (ENSG00000170545), CADM2 (ENSG00000175161), NECTIN3 (ENSG00000177707), TIGIT (ENSG00000181847), CADM1 (ENSG00000182985), NCR3 (ENSG00000204475)

Protein

Protein identifiers

Nectin-4 — Q96NY8 (reviewed: Q96NY8)

Alternative names: Ig superfamily receptor LNIR, Nectin cell adhesion molecule 4, Poliovirus receptor-related protein 4

All UniProt accessions (2): Q96NY8, K4PZ75

UniProt curated annotations — full annotation on UniProt →

Function. Seems to be involved in cell adhesion through trans-homophilic and -heterophilic interactions, the latter including specifically interactions with NECTIN1. Does not act as receptor for alpha-herpesvirus entry into cells. (Microbial infection) Acts as a receptor for measles virus.

Subunit / interactions. Self-associates. Interacts via its Ig-like V-type domain with NECTIN1 Ig-like V-type domain. Interacts via its C-terminus with AFDN. (Microbial infection) Interacts (via N-terminus) with measles virus hemagglutinin protein.

Subcellular location. Cell membrane. Cell junction. Adherens junction Secreted.

Tissue specificity. Predominantly expressed in placenta. Not detected in normal breast epithelium but expressed in breast carcinoma.

Post-translational modifications. The soluble form is produced by proteolytic cleavage at the cell surface (shedding), probably by ADAM17/TACE.

Disease relevance. Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) [MIM:613573] A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EDSS1 is characterized by the association of hair and teeth abnormalities with cutaneous syndactyly of the hands and/or feet. Hair morphologic abnormalities include twists at irregular intervals (pilli torti) and swelling along the shafts, particularly associated with areas of breakage. Dental findings consist of abnormally widely spaced teeth, with peg-shaped and conical crowns. Patients have normal sweating. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the nectin family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q96NY8-1	1	yes
Q96NY8-2	2

RefSeq proteins (1): NP_112178* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013162	CD80_C2-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR033320	IgC1_2_Nectin-3-4-like	Domain
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR051427	Nectin/Nectin-like	Family

Pfam: PF07686, PF08205, PF13927

UniProt features (42 total): strand 16, disulfide bond 3, helix 3, domain 3, chain 2, region of interest 2, splice variant 2, sequence variant 2, turn 2, topological domain 2, signal peptide 1, compositionally biased region 1, glycosylation site 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
4JJH	X-RAY DIFFRACTION	2.25
9UCL	ELECTRON MICROSCOPY	2.43
4GJT	X-RAY DIFFRACTION	3.1
9KKJ	ELECTRON MICROSCOPY	3.26
4FRW	X-RAY DIFFRACTION	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96NY8-F1	79.79	0.52

Antibody-complex structures (SAbDab): 1 — 9KKJ

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 (3): 52–127, 171–223, 270–315

Glycosylation sites (1): 281

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-418990	Adherens junctions interactions
R-HSA-420597	Nectin/Necl trans heterodimerization
R-HSA-1500931	Cell-Cell communication
R-HSA-421270	Cell-cell junction organization
R-HSA-446728	Cell junction organization

MSigDB gene sets: 284 (showing top): GOBP_HETEROPHILIC_CELL_CELL_ADHESION, GCANCTGNY_MYOD_Q6, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, AREB6_03, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_LEUKOCYTE_MEDIATED_CYTOTOXICITY, GOBP_NEGATIVE_REGULATION_OF_NATURAL_KILLER_CELL_MEDIATED_IMMUNITY, GGGTGGRR_PAX4_03, GOBP_LEUKOCYTE_MEDIATED_IMMUNITY, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_NEGATIVE_REGULATION_OF_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_CELL_CELL_ADHESION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, RICKMAN_METASTASIS_DN, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM

GO Biological Process (6): homophilic cell-cell adhesion (GO:0007156), heterophilic cell-cell adhesion (GO:0007157), negative regulation of natural killer cell mediated cytotoxicity (GO:0045953), cell adhesion (GO:0007155), signal transduction (GO:0007165), symbiont entry into host cell (GO:0046718)

GO Molecular Function (5): virus receptor activity (GO:0001618), identical protein binding (GO:0042802), receptor ligand activity (GO:0048018), cell adhesion mediator activity (GO:0098631), protein binding (GO:0005515)

GO Cellular Component (6): plasma membrane (GO:0005886), adherens junction (GO:0005912), extracellular exosome (GO:0070062), extracellular region (GO:0005576), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Cell-cell junction organization	1
Adherens junctions interactions	1
Cell junction organization	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell-cell adhesion	2
cellular process	2
cellular anatomical structure	2
negative regulation of leukocyte mediated cytotoxicity	1
negative regulation of natural killer cell mediated immunity	1
natural killer cell mediated cytotoxicity	1
regulation of natural killer cell mediated cytotoxicity	1
cell communication	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
viral life cycle	1
symbiont entry into host	1
symbiont entry into host cell	1
exogenous protein binding	1
protein binding	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
cell adhesion	1
cell adhesion molecule binding	1
binding	1
membrane	1
cell periphery	1
cell-cell junction	1
extracellular vesicle	1
cell junction	1

Protein interactions and networks

STRING

790 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NECTIN4	MYBPH	Q13203	993
NECTIN4	AFDN	P55196	967
NECTIN4	SLAMF1	Q13291	845
NECTIN4	CD46	P15529	797
NECTIN4	ADAM17	P78536	675
NECTIN4	ITGB4	P16144	668
NECTIN4	NECTIN1	Q15223	621
NECTIN4	TACSTD2	P09758	582
NECTIN4	CD226	Q15762	582
NECTIN4	CD96	P40200	579
NECTIN4	PVRIG	Q6DKI7	522
NECTIN4	ERVW-1	Q9UQF0	502
NECTIN4	CD79B	P40259	451
NECTIN4	KLHDC9	Q8NEP7	450
NECTIN4	SLAMF6	Q96DU3	446

IntAct

31 interactions, top by confidence:

A	B	Type	Score
NECTIN1	NECTIN4	psi-mi:“MI:0407”(direct interaction)	0.760
NECTIN1	NECTIN4	psi-mi:“MI:0915”(physical association)	0.760
NECTIN4	NECTIN1	psi-mi:“MI:0915”(physical association)	0.760
NECTIN4	H	psi-mi:“MI:0407”(direct interaction)	0.720
NECTIN4	H	psi-mi:“MI:0915”(physical association)	0.720
H	NECTIN4	psi-mi:“MI:0407”(direct interaction)	0.720
NECTIN4	NECTIN4	psi-mi:“MI:0407”(direct interaction)	0.620
ZNF582	NECTIN4	psi-mi:“MI:0915”(physical association)	0.590
ERH	SNRPD3	psi-mi:“MI:0914”(association)	0.580
DEFB121	NECTIN4	psi-mi:“MI:0915”(physical association)	0.560
NECTIN4	EIF2B2	psi-mi:“MI:0914”(association)	0.530
STING1	NECTIN4	psi-mi:“MI:0915”(physical association)	0.400
NECTIN4	NECTIN2	psi-mi:“MI:0915”(physical association)	0.400
NECTIN4	TIGIT	psi-mi:“MI:0915”(physical association)	0.400
Pick1	NECTIN4	psi-mi:“MI:0915”(physical association)	0.370
AFDN	NECTIN4	psi-mi:“MI:0915”(physical association)	0.370
NECTIN4	GLB1	psi-mi:“MI:0914”(association)	0.350
NECTIN4	EIF2B5	psi-mi:“MI:0914”(association)	0.350
INSR	BLTP3B	psi-mi:“MI:0914”(association)	0.350
CDH1	ESYT2	psi-mi:“MI:2364”(proximity)	0.270
DEFB121	NECTIN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (50): EIF2B4 (Affinity Capture-MS), PDSS1 (Affinity Capture-MS), FBXO10 (Affinity Capture-MS), EIF2B1 (Affinity Capture-MS), PIGU (Affinity Capture-MS), C6orf62 (Affinity Capture-MS), ENAH (Affinity Capture-MS), EVL (Affinity Capture-MS), CTSA (Affinity Capture-MS), EIF2B2 (Affinity Capture-MS), EIF2B3 (Affinity Capture-MS), RRP1 (Affinity Capture-MS), PVRL4 (Affinity Capture-MS), PVRL4 (Proximity Label-MS), PDSS1 (Affinity Capture-MS)

ESM2 similar proteins: A0JNA2, A4FUY1, C0HL12, O14514, O19131, O60241, O75325, P0C5H6, P15151, P32506, P32507, P70225, P98095, Q05BQ1, Q13477, Q14626, Q14CZ8, Q29RN8, Q3UHD1, Q4V9Z5, Q53EL9, Q5DRQ8, Q5R7Y0, Q5RF19, Q5STE3, Q63148, Q64385, Q6AX42, Q6BAA4, Q6MZW2, Q6UWL2, Q6UWL6, Q6UXD5, Q6WN34, Q7TSK2, Q7TSU7, Q8BHA1, Q8BQC3, Q8CGM1, Q8IVU1

Diamond homologs: A0A0B4J1L0, A0A140LHF2, D3ZQE1, E9QA28, O75871, P06731, P11464, P11465, P13688, P16573, P31809, P31997, P35329, P40198, P40199, Q00887, Q00888, Q00889, Q13046, Q14002, Q15238, Q16557, Q2WEN9, Q3KPI0, Q4VAH7, Q61400, Q63111, Q7TPB4, Q810J1, Q8R007, Q8R2Y2, Q8VE98, Q925P2, Q96NY8, Q9UQ72, Q9UQ74, A8MVW5, Q28730, Q28824, Q60625

SIGNOR signaling

0 interactions.

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	10
Likely pathogenic	2
Uncertain significance	23
Likely benign	33
Benign	12

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1600	NM_030916.3(NECTIN4):c.851G>A (p.Arg284Gln)	Pathogenic
1601	NM_030916.3(NECTIN4):c.554C>T (p.Thr185Met)	Pathogenic
1602	NM_030916.3(NECTIN4):c.906del (p.Pro304fs)	Pathogenic
30794	NM_030916.3(NECTIN4):c.635C>G (p.Pro212Arg)	Pathogenic
3613989	NM_030916.3(NECTIN4):c.1117C>T (p.Arg373Ter)	Pathogenic
425551	NM_030916.3(NECTIN4):c.724G>A (p.Val242Met)	Pathogenic
425552	NM_030916.3(NECTIN4):c.181C>T (p.Gln61Ter)	Pathogenic
4717321	NM_030916.3(NECTIN4):c.242dup (p.Leu82fs)	Pathogenic
807665	NM_030916.3(NECTIN4):c.229C>T (p.Gln77Ter)	Pathogenic
996828	NM_030916.3(NECTIN4):c.880C>T (p.Arg294Ter)	Pathogenic
1324796	NM_030916.3(NECTIN4):c.1233+1G>A	Likely pathogenic
3393124	NM_030916.3(NECTIN4):c.1516C>T (p.Arg506Trp)	Likely pathogenic

SpliceAI

1364 predictions. Top by Δscore:

Variant	Effect	Δscore
1:161072894:C:CT	acceptor_gain	1.0000
1:161073718:ACC:A	donor_loss	1.0000
1:161073719:C:T	donor_loss	1.0000
1:161073792:CTCA:C	acceptor_gain	1.0000
1:161073794:CA:C	acceptor_gain	1.0000
1:161073794:CACTG:C	acceptor_loss	1.0000
1:161073795:ACTGG:A	acceptor_loss	1.0000
1:161073796:C:CC	acceptor_gain	1.0000
1:161073796:CTGGG:C	acceptor_loss	1.0000
1:161074209:GTACT:G	donor_loss	1.0000
1:161074213:TCA:T	donor_loss	1.0000
1:161074214:CAC:C	donor_loss	1.0000
1:161074215:A:AC	donor_gain	1.0000
1:161074215:AC:A	donor_loss	1.0000
1:161074216:C:CA	donor_gain	1.0000
1:161074216:CT:C	donor_gain	1.0000
1:161074216:CTA:C	donor_gain	1.0000
1:161074216:CTAT:C	donor_gain	1.0000
1:161074216:CTATT:C	donor_gain	1.0000
1:161074282:C:CT	acceptor_gain	1.0000
1:161076476:C:CC	acceptor_gain	1.0000
1:161077447:A:AC	donor_gain	1.0000
1:161077448:C:CC	donor_gain	1.0000
1:161077449:TTA:T	donor_loss	1.0000
1:161077450:TAC:T	donor_loss	1.0000
1:161077451:A:AC	donor_gain	1.0000
1:161077451:A:T	donor_loss	1.0000
1:161077452:C:A	donor_loss	1.0000
1:161077452:C:CA	donor_gain	1.0000
1:161077452:CA:C	donor_gain	1.0000

AlphaMissense

3268 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:161076360:C:A	W282C	1.000
1:161076360:C:G	W282C	1.000
1:161077515:C:G	C223S	1.000
1:161077516:A:T	C223S	1.000
1:161077634:C:A	W183C	1.000
1:161077634:C:G	W183C	1.000
1:161077636:A:G	W183R	1.000
1:161077636:A:T	W183R	1.000
1:161077671:C:G	C171S	1.000
1:161077672:A:T	C171S	1.000
1:161072740:A:C	F485C	0.999
1:161074667:C:G	C315S	0.999
1:161074667:C:T	C315Y	0.999
1:161074668:A:G	C315R	0.999
1:161074668:A:T	C315S	0.999
1:161076362:A:G	W282R	0.999
1:161076362:A:T	W282R	0.999
1:161076397:C:G	C270S	0.999
1:161076398:A:G	C270R	0.999
1:161076398:A:T	C270S	0.999
1:161077514:A:C	C223W	0.999
1:161077515:C:T	C223Y	0.999
1:161077516:A:G	C223R	0.999
1:161077560:A:G	F208S	0.999
1:161077670:G:C	C171W	0.999
1:161077671:C:T	C171Y	0.999
1:161077672:A:G	C171R	0.999
1:161079649:C:G	C127S	0.999
1:161079650:A:T	C127S	0.999
1:161079828:C:A	W67C	0.999

dbSNP variants (sampled 300 via entrez): RS1000010464 (1:161084028 G>C), RS1000082792 (1:161086461 G>A), RS1000581348 (1:161091158 G>A,C), RS1000738008 (1:161090806 A>G), RS1000838954 (1:161077628 C>A,G,T), RS1001069849 (1:161071389 A>G), RS1001376365 (1:161077963 A>G), RS1001838416 (1:161071824 A>C,T), RS1001891554 (1:161078340 G>A), RS1001917888 (1:161073238 C>T), RS1001943041 (1:161072531 G>A), RS1002119825 (1:161084291 A>C,G), RS1002224699 (1:161091240 G>A), RS1002243543 (1:161079459 G>A,C), RS1002250465 (1:161089467 C>G,T)

Disease associations

OMIM: gene MIM:609607 | disease phenotypes: MIM:613573

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia-syndactyly syndrome 1	Definitive	Autosomal recessive
ectodermal dysplasia-syndactyly syndrome	Supportive	Autosomal recessive

Mondo (2): ectodermal dysplasia-syndactyly syndrome 1 (MONDO:0024565), ectodermal dysplasia-syndactyly syndrome (MONDO:0013311)

Orphanet (1): Ectodermal dysplasia-pili torti-cutaneous syndactyly syndrome (Orphanet:247820)

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000653	Sparse eyelashes
HP:0000687	Widely spaced teeth
HP:0000698	Conical tooth
HP:0000968	Ectodermal dysplasia
HP:0001596	Alopecia
HP:0001792	Small nail
HP:0001800	Hypoplastic toenails
HP:0002046	Heat intolerance
HP:0002208	Coarse hair
HP:0002209	Sparse scalp hair
HP:0002232	Patchy alopecia
HP:0002550	Absent facial hair
HP:0003577	Congenital onset
HP:0003777	Pili torti
HP:0004692	4-5 toe syndactyly
HP:0005709	2-3 toe cutaneous syndactyly
HP:0006297	Enamel hypoplasia
HP:0010554	Cutaneous finger syndactyly
HP:0010709	2-4 finger cutaneous syndactyly
HP:0010765	Palmar hyperkeratosis

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003542_114	Night sleep phenotypes	7.000000e-06
GCST003542_135	Night sleep phenotypes	4.000000e-06
GCST011124_22	Caffeine consumption from tea	7.000000e-13

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0010091	tea consumption measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712928 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs11265549	Toxicity	3	methadone	Opioid-Related Disorders;Pruritus
rs11265549	Dosage	3	methadone	Opioid-Related Disorders
rs11265549	Metabolism/PK	3	methadone	Opioid-Related Disorders

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs11265549	NECTIN4	3	2.75	3	methadone

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: other protein — Immunoglobulin C2-set domain-containing proteins

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
BT7480	Binding	8.29	pKd

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
9.17	EC50	0.67	nM	CHEMBL5193789
8.62	Ki	2.4	nM	CHEMBL5218456
8.62	Ki	2.4	nM	CHEMBL5220448
8.60	Kd	2.5	nM	CHEMBL5219064
8.55	Kd	2.8	nM	CHEMBL5202442
8.55	Ki	2.8	nM	CHEMBL5218740
8.31	Ki	4.9	nM	CHEMBL5220463
8.28	Ki	5.2	nM	CHEMBL5220631
8.21	Ki	6.1	nM	CHEMBL5220922
8.06	Ki	8.8	nM	CHEMBL5219136
8.01	Ki	9.7	nM	CHEMBL5220083
7.94	Ki	11.5	nM	CHEMBL5219641
7.88	Ki	13.2	nM	CHEMBL5220023
7.87	Ki	13.5	nM	CHEMBL5220092
7.87	Ki	13.4	nM	CHEMBL5221012
7.85	EC50	14	nM	CHEMBL5202254
7.79	Ki	16.3	nM	CHEMBL5219400
7.75	Ki	17.6	nM	CHEMBL5220320
7.71	Ki	19.4	nM	CHEMBL5220037
7.62	Ki	23.9	nM	CHEMBL5218904
7.56	Ki	27.3	nM	CHEMBL5219498
7.56	Ki	27.4	nM	CHEMBL5220040
7.56	Ki	27.3	nM	CHEMBL5220458
7.55	Ki	28	nM	CHEMBL5220510
7.50	Ki	31.4	nM	CHEMBL5220499
7.43	Ki	37.3	nM	CHEMBL5219259
7.43	Ki	37.5	nM	CHEMBL5218678
7.41	Ki	38.6	nM	CHEMBL5221108
7.41	Ki	38.7	nM	CHEMBL5220688
7.35	Ki	44.3	nM	CHEMBL5219916
7.33	Ki	46.8	nM	CHEMBL5219402
7.33	Ki	46.4	nM	CHEMBL5219878
7.24	Ki	57.6	nM	CHEMBL5220400
7.23	Ki	59.2	nM	CHEMBL5220633
7.19	Ki	64.2	nM	CHEMBL5221095
7.17	Ki	66.9	nM	CHEMBL5220747
7.16	Ki	68.9	nM	CHEMBL5218503
7.16	Ki	69.8	nM	CHEMBL5218565
7.12	Ki	76.1	nM	CHEMBL5220697
7.11	Ki	77.7	nM	CHEMBL5220678
7.09	Ki	81.1	nM	CHEMBL5220964
6.85	Ki	142	nM	CHEMBL5219480
6.80	Ki	158	nM	CHEMBL5220777
6.75	Ki	176	nM	CHEMBL5218845
6.73	Ki	185	nM	CHEMBL5219726
6.70	Ki	202	nM	CHEMBL5220813
6.54	Ki	286	nM	CHEMBL5218816
6.22	Ki	606	nM	CHEMBL5220830
6.16	Ki	694	nM	CHEMBL5219369
6.13	Ki	737	nM	CHEMBL5219755

PubChem BioAssay actives

50 with measured affinity, of 56 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
3-[(9R,12S,18S,21S,24R,30S,33S,36R,39S,42S,45S,51S,54S,57S,60R)-9-acetamido-24-[4-[3-[1-[2-[2-[2-[2-[2-[3-[4-[(9R,12S,15S,17R,21S,27S,30S,33S,36S,39S,42S,45R,48R,51S,54S,60R)-60-acetamido-39-(4-carbamimidamidobutyl)-9-carbamoyl-17-hydroxy-27-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-36-(1H-imidazol-4-ylmethyl)-12,33-bis(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-51-(naphthalen-1-ylmethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontan-48-yl]butylamino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]propanoylamino]butyl]-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-39-benzyl-57-butyl-45-(carboxymethyl)-12-(2,2-dimethylpropyl)-33,54-bis[(4-hydroxyphenyl)methyl]-42-methyl-4,10,13,19,22,25,31,34,37,40,43,46,52,55,58,65,68-heptadecaoxo-7,62,71-trithia-1,3,11,14,20,23,26,32,35,38,41,44,47,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.014,18.026,30.047,51]triheptacontan-21-yl]propanoic acid	1893343: Agonist activity at human Nectin-4 expressed in Jurkat T cells co-expressing response element driven luciferase reporter gene assessed as luminescence measured after 6 hrs by HT1376/CD137 reporter co-culture assay	ec50	0.0007	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-48-(naphthalen-1-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0024	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-48-(naphthalen-2-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0024	uM
(3S)-4-[[(9R,13R,18S,21S,24S,30S,33S,36R,39S,42S,51S,54S,57S,63R)-24-(2-amino-2-oxoethyl)-60-(4-carbamimidamidobutyl)-63-carbamoyl-51-(carboxymethyl)-13-hydroxy-42-(1H-imidazol-4-ylmethyl)-54,57-bis(1H-indol-3-ylmethyl)-18,33,39-tris(2-methylpropyl)-4,10,16,19,22,25,31,34,37,40,43,49,52,55,58,61,68,73-octadecaoxo-21-propan-2-yl-7,65,74-trithia-1,3,11,17,20,23,26,32,35,38,41,44,50,53,56,59,62,69-octadecazahexacyclo[34.34.5.13,69.011,15.026,30.044,48]hexaheptacontan-9-yl]amino]-3-[[(2S)-6-carbamimidamido-2-[[(1S)-1-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[3-[[5-[[(2S)-1-[[(2S)-5-(carbamoylamino)-1-[4-[[[(2S)-1-[[(2S)-1-[[(3S,4S,5S)-1-[2-[(1S,2S)-3-[[(1R,2S)-1-hydroxy-1-phenylpropan-2-yl]amino]-1-methoxy-2-methyl-3-oxopropyl]pyrrolidin-1-yl]-3-methoxy-5-methyl-1-oxoheptan-4-yl]-methylamino]-3-methyl-1-oxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]-methylcarbamoyl]oxymethyl]anilino]-1-oxopentan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-5-oxopentanoyl]amino]propanoyl-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]-methylamino]acetyl]amino]ethyl]amino]hexanoyl]amino]-4-oxobutanoic acid	1917820: Binding affinity to C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as dissociation constant by SPR assay	kd	0.0025	uM
3-[(9R,12S,15S,18S,24S,27S,30S,33R,36S,39S,45S,48S,54R)-54-[[(2S)-2-acetamidopropanoyl]amino]-9-[[(2S)-1-amino-3-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[4-[3-[[3-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[2-[[(9R,12S,15S,17R,21S,27S,30S,33S,36S,39S,42S,45R,48R,51S,54S,60R)-39-(4-carbamimidamidobutyl)-9-carbamoyl-36,48-bis(carboxymethyl)-17-hydroxy-27-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-12,33-bis(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-51-(naphthalen-1-ylmethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontan-60-yl]amino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-2-oxoethyl]-methylamino]-3-oxopropyl]amino]-3-oxopropyl]triazol-1-yl]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]-1-oxopropan-2-yl]carbamoyl]-39-(3-amino-3-oxopropyl)-30-benzyl-51-[(2S)-butan-2-yl]-12-butyl-48-(2-carboxyethyl)-24-(carboxymethyl)-15,36-bis[(4-hydroxyphenyl)methyl]-27-methyl-4,11,14,17,23,26,29,32,35,38,41,44,47,50,53,59,62-heptadecaoxo-7,56,65-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,52,60-heptadecazatetracyclo[31.28.5.13,60.018,22]heptahexacontan-45-yl]propanoic acid	1893344: Binding affinity to human Nectin-4 assessed as dissociation constant using 1:1 Nectin-4/CD137 by surface plasmon resonance analysis	kd	0.0028	uM
(9R,12S,15S,21S,27S,30S,33S,36S,39S,42S,45R,48R,51S,54S,60S)-60-acetamido-39-(4-carbamimidamidobutyl)-36,48-bis(carboxymethyl)-17-hydroxy-27-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-12,33-bis(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-51-(naphthalen-1-ylmethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0028	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-30-[(5-fluoro-1H-indol-3-yl)methyl]-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12-(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0049	uM
(9R,12S,15S,17R,21S,27S,30S,33S,36S,39S,42S,45R,48R,51S,54S,60S)-60-acetamido-36-(2-amino-2-oxoethyl)-39-(4-carbamimidamidobutyl)-48-(carboxymethyl)-17-hydroxy-27-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-12,33-bis(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-51-(pyridin-2-ylmethyl)-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0052	uM
(9R,12S,15S,21S,27S,30S,33S,36S,39S,42S,45R,48R,51S,54S,60S)-60-acetamido-36-(2-amino-2-oxoethyl)-39-(4-carbamimidamidobutyl)-48-(carboxymethyl)-27-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-12,33-bis(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-51-(pyridin-2-ylmethyl)-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0061	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0088	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-12-[(5-fluoro-1H-indol-3-yl)methyl]-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-30-(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0097	uM
(9R,12S,15S,21S,27S,30S,33S,36S,39S,42S,45R,51S,54S,60S)-60-acetamido-39-(4-aminobutyl)-36-(2-amino-2-oxoethyl)-30-(hydroxymethyl)-12,27,33-tris(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-51-(pyridin-2-ylmethyl)-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0115	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-45-(carboxymethyl)-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0132	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-48-[(3-methylphenyl)methyl]-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0134	uM
(2S)-2-[[(2S,3R)-2-[[(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carbonyl]amino]-3-hydroxybutanoyl]amino]-N-[(2S)-1,6-diamino-1-oxohexan-2-yl]butanediamide	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0135	uM
3-[(9R,12S,18S,21S,24R,30S,33S,36R,39S,42S,45S,51S,54S,57S,60R)-9-acetamido-60-[[(2S)-1-amino-1-oxopropan-2-yl]carbamoyl]-39-benzyl-24-[4-[3-[1-[2-[2-[2-[2-[2-[3-[[(9R,12S,15S,17R,21S,27S,30S,33S,36S,39S,42S,45R,51S,54S,60R)-51-benzyl-39-(4-carbamimidamidobutyl)-9-carbamoyl-36-(carboxymethyl)-17-hydroxy-27-[(1R)-1-hydroxyethyl]-30-(hydroxymethyl)-12,33-bis(1H-indol-3-ylmethyl)-42-(2-methylsulfanylethyl)-4,11,14,20,26,29,32,35,38,41,44,47,50,53,59,65,68-heptadecaoxo-7,62,71-trithia-1,3,10,13,19,25,28,31,34,37,40,43,46,49,52,58,66-heptadecazahexacyclo[43.22.5.13,66.015,19.021,25.054,58]triheptacontan-60-yl]amino]-3-oxopropoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]triazol-4-yl]propanoylamino]butyl]-57-butyl-45-(carboxymethyl)-12-(2,2-dimethylpropyl)-33,54-bis[(4-hydroxyphenyl)methyl]-42-methyl-4,10,13,19,22,25,31,34,37,40,43,46,52,55,58,65,68-heptadecaoxo-7,62,71-trithia-1,3,11,14,20,23,26,32,35,38,41,44,47,53,56,59,66-heptadecazahexacyclo[34.31.5.13,66.014,18.026,30.047,51]triheptacontan-21-yl]propanoic acid	1893343: Agonist activity at human Nectin-4 expressed in Jurkat T cells co-expressing response element driven luciferase reporter gene assessed as luminescence measured after 6 hrs by HT1376/CD137 reporter co-culture assay	ec50	0.0140	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-33-(1H-imidazol-4-ylmethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0163	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0176	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-48-[(4-methylphenyl)methyl]-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0194	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0239	uM
(2S)-2-[[(2S,3R)-2-[[(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-57-[[(2S)-2-aminopropanoyl]amino]-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carbonyl]amino]-3-hydroxybutanoyl]amino]-N-[(2S)-1,6-diamino-1-oxohexan-2-yl]butanediamide	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0273	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-24,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-12-(naphthalen-2-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0273	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-15-[(2S)-butan-2-yl]-33-(carboxymethyl)-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0274	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-24-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0280	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0314	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-acetamidobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0373	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-24-(naphthalen-2-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0375	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-39-[(2R)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0386	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylpropyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0387	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfonylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0443	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-53-oxa-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0464	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-39-(3-amino-3-oxopropyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0468	uM
(2S)-2-[[(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-57-[[(2S)-2-aminopropanoyl]amino]-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carbonyl]amino]propanoic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0576	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-30-(naphthalen-1-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0592	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-39-(2,2-dimethylpropyl)-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0642	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,56S)-56-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,55,61,64-heptadecaoxo-7,58,67-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,54,62-heptadecazapentacyclo[40.21.5.13,62.018,22.051,54]nonahexacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0669	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(3-methylbutyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0689	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-24-(naphthalen-1-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0698	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-24,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-12-(naphthalen-1-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0761	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(carboxymethyl)-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0777	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-(carboxymethyl)-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.0811	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-30-(naphthalen-2-ylmethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.1420	uM
(9R,12S,15S,18S,20S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-20-hydroxy-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.1580	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-3-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.1760	uM
(9R,12S,15S,18S,23S,26S,29S,32S,35S,38S,41R,47S,50S,56S)-56-acetamido-35-(4-aminobutyl)-32-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-26-(hydroxymethyl)-12,23,29-tris(1H-indol-3-ylmethyl)-38-(2-methylsulfanylethyl)-4,11,14,17,22,25,28,31,34,37,40,43,46,49,55,61,64-heptadecaoxo-47-(pyridin-2-ylmethyl)-7,58,67-trithia-1,3,10,13,16,21,24,27,30,33,36,39,42,45,48,54,62-heptadecazapentacyclo[39.22.5.13,62.018,21.050,54]nonahexacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.1850	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,45R,48S,51S,57S)-57-acetamido-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-36-(4-carbamimidamidobutyl)-45-(carboxymethyl)-24-[(1R)-1-hydroxyethyl]-27-(hydroxymethyl)-12,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-20-oxa-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.2020	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-24,30-bis(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-12-(1H-pyrrolo[2,3-b]pyridin-3-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.2860	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-48-(pyridin-2-ylmethyl)-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.6060	uM
(9R,12S,15S,18S,25S,28S,31S,34S,37S,40S,43R,49S,52S,58S)-58-acetamido-37-(4-aminobutyl)-34-(2-amino-2-oxoethyl)-15-[(2S)-butan-2-yl]-24-hydroxy-28-(hydroxymethyl)-12,25,31-tris(1H-indol-3-ylmethyl)-40-(2-methylsulfanylethyl)-4,11,14,17,27,30,33,36,39,42,45,48,51,57,63,66-hexadecaoxo-49-(pyridin-2-ylmethyl)-7,60,69-trithia-1,3,10,13,16,23,26,29,32,35,38,41,44,47,50,56,64-heptadecazapentacyclo[41.22.5.13,64.018,23.052,56]henheptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.6940	uM
(9R,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R,48S,51S,53R,57S)-57-acetamido-36-(4-aminobutyl)-33-(2-amino-2-oxoethyl)-48-benzyl-15-[(2S)-butan-2-yl]-53-hydroxy-27-(hydroxymethyl)-12,24,30-tris(1H-indol-3-ylmethyl)-39-(2-methylsulfanylethyl)-4,11,14,17,23,26,29,32,35,38,41,44,47,50,56,62,65-heptadecaoxo-7,59,68-trithia-1,3,10,13,16,22,25,28,31,34,37,40,43,46,49,55,63-heptadecazapentacyclo[40.22.5.13,63.018,22.051,55]heptacontane-9-carboxylic acid	1917815: Displacement of tracer from C-terminal FLAG-tagged human Nectin-4 (32 to 349 residues) expressed in baculovirus infected sf9 cells assessed as inhibition constant measured at 5 to 10 mins interval for 60 mins by fluorescence polarization assay	ki	0.7370	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Aflatoxin B1	increases methylation, affects expression, increases expression	7
Benzo(a)pyrene	decreases expression, decreases methylation, increases expression, increases methylation	6
Particulate Matter	affects methylation, increases abundance, increases expression	4
Air Pollutants	affects methylation, increases abundance, increases expression	3
Estradiol	affects cotreatment, decreases expression	3
lasiocarpine	increases expression	2
methyleugenol	increases expression	2
sodium arsenite	increases expression	2
mercuric bromide	increases expression, affects cotreatment	2
Formaldehyde	increases expression, decreases expression	2
N-Nitrosopyrrolidine	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	affects expression, decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
aristolochic acid I	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	increases expression	1
propionaldehyde	increases expression	1
pirinixic acid	decreases expression	1
bisphenol A	decreases expression	1
kojic acid	increases expression	1
butyraldehyde	increases expression	1
zinc chromate	increases expression, increases abundance	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
dibenzo(a,l)pyrene	decreases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
clothianidin	decreases expression	1
abrine	increases expression	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5149477	Binding	Agonist activity at human Nectin-4 expressed in Jurkat T cells co-expressing response element driven luciferase reporter gene assessed as luminescence measured after 6 hrs by HT1376/CD137 reporter co-culture assay	Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 cancer cell line, 2 spontaneously immortalized cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E0IV	Ubigene HeLa NECTIN4 KO	Cancer cell line	Female
CVCL_E1CI	Ubigene SW780 NECTIN4 KO	Cancer cell line	Female
CVCL_E6RD	Genomeditech CHO-K1 H_NECTIN4	Spontaneously immortalized cell line	Female
CVCL_E6UQ	Genomeditech HEK-293 H_NECTIN4	Transformed cell line	Female
CVCL_E8DJ	BPS Bioscience MCF-7 NECTIN4 KO	Cancer cell line	Female
CVCL_RR11	MCF10A PVRL4 (-/-)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

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