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: 2
• Clinical variants (ClinVar): 93 total — 10 pathogenic, 2 likely-pathogenic
• GTEx eGene: eQTL in 6 tissues, sQTL in 5 (q < 0.05)
• Phenotypes (HPO): 21
• Drug target: yes — 1 curated mechanism-of-action drug
• Approved drugs (ChEMBL mechanism of action): 1 — Enfortumab Vedotin
• Constraint (gnomAD): pLI 0.86 (intermediate), LOEUF 0.54 (moderately constrained)
• 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: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000368012

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

ENST00000368012, ENST00000486694, ENST00000891630, ENST00000968999, ENST00001142179

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.

Highest expression (Bgee): lower esophagus mucosa, skin of abdomen, skin of leg, esophagus mucosa, zone of skin.

Genetic regulation across tissues (GTEx eQTL / sQTL)

NECTIN4 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 6 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

11 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Skin Sun Exposed Lower leg	sqtl	6.5e-71	+1.09	1:161076995:G:GC
Skin Not Sun Exposed Suprapubic	sqtl	1.9e-38	+2.10	1:161074389:C:T
Minor Salivary Gland	sqtl	6.5e-04	-0.83	1:161076995:G:GC
Esophagus Mucosa	sqtl	2.8e-03	+0.28	1:161073084:AGCAGAGATGCGGT:A
Pituitary	eqtl	1.2e-02	+0.64	1:160559625:A:G
Cells Cultured fibroblasts	eqtl	2.1e-02	-0.19	1:161068977:T:C
Stomach	sqtl	2.3e-02	+1.57	1:161378034:T:A
Testis	eqtl	2.4e-02	+0.24	1:161077335:CTATA:C
Esophagus Gastroesophageal Junction	eqtl	3.1e-02	-0.75	1:160476410:G:A
Artery Tibial	eqtl	4.0e-02	-0.28	1:161022031:A:C
Skin Sun Exposed Lower leg	eqtl	4.4e-02	+0.07	1:160862422:A:G

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

showing 100 of 245 tissues 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
gall bladder	UBERON:0002110	74.69	gold quality
penis	UBERON:0000989	74.16	gold quality
body of pancreas	UBERON:0001150	73.58	gold quality
urinary bladder	UBERON:0001255	73.44	gold quality
prostate gland	UBERON:0002367	73.34	gold quality
right uterine tube	UBERON:0001302	72.62	gold quality
tibialis anterior	UBERON:0001385	72.26	silver quality
esophagus	UBERON:0001043	71.97	gold quality
kidney epithelium	UBERON:0004819	71.97	gold quality
skin of hip	UBERON:0001554	71.89	gold quality
body of stomach	UBERON:0001161	70.22	gold quality
bronchial epithelial cell	CL:0002328	70.20	gold quality
body of tongue	UBERON:0011876	70.06	silver quality
bronchus	UBERON:0002185	69.81	gold quality
epithelium of nasopharynx	UBERON:0001951	69.80	silver quality
epithelium of mammary gland	UBERON:0003244	69.60	silver quality
mammary duct	UBERON:0001765	69.55	silver quality
mucosa of paranasal sinus	UBERON:0005030	69.42	gold quality
right lung	UBERON:0002167	69.34	gold quality
mucosa of transverse colon	UBERON:0004991	69.21	gold quality
stomach	UBERON:0000945	68.63	gold quality
upper lobe of left lung	UBERON:0008952	68.37	gold quality
metanephros cortex	UBERON:0010533	67.06	gold quality
rectum	UBERON:0001052	66.91	gold quality
upper lobe of lung	UBERON:0008948	66.35	gold quality
epithelial cell of pancreas	CL:0000083	66.29	gold quality
trachea	UBERON:0003126	65.86	silver quality
tongue	UBERON:0001723	65.72	silver quality
mucosa of stomach	UBERON:0001199	65.44	gold quality
thoracic mammary gland	UBERON:0005200	65.19	gold quality
mammary gland	UBERON:0001911	65.13	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	65.13	gold quality
trabecular bone tissue	UBERON:0002483	64.35	gold quality
biceps brachii	UBERON:0001507	63.71	gold quality
superior surface of tongue	UBERON:0007371	63.48	gold quality
decidua	UBERON:0002450	63.45	silver quality
colonic epithelium	UBERON:0000397	63.30	silver quality
ileal mucosa	UBERON:0000331	63.29	silver quality
urethra	UBERON:0000057	63.06	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	62.25	gold quality
fundus of stomach	UBERON:0001160	61.94	gold quality
adult mammalian kidney	UBERON:0000082	61.88	gold quality
deltoid	UBERON:0001476	61.54	gold quality
transverse colon	UBERON:0001157	61.51	gold quality
cartilage tissue	UBERON:0002418	61.28	gold quality
layer of synovial tissue	UBERON:0007616	61.24	gold quality
colonic mucosa	UBERON:0000317	61.21	gold quality
endometrium	UBERON:0001295	61.15	gold quality
heart right ventricle	UBERON:0002080	60.98	gold quality
uterine cervix	UBERON:0000002	60.73	gold quality
lung	UBERON:0002048	60.71	gold quality
corpus epididymis	UBERON:0004359	60.66	gold quality
mucosa of sigmoid colon	UBERON:0004993	60.45	gold quality
kidney	UBERON:0002113	59.56	gold quality
caput epididymis	UBERON:0004358	59.15	silver quality
female reproductive system	UBERON:0000474	59.04	gold quality
thymus	UBERON:0002370	58.79	gold quality
metanephros	UBERON:0000081	58.68	gold quality
Brodmann (1909) area 23	UBERON:0013554	58.62	gold quality
vena cava	UBERON:0004087	58.47	gold quality
middle temporal gyrus	UBERON:0002771	58.06	gold quality
bone marrow	UBERON:0002371	57.72	silver quality
saphenous vein	UBERON:0007318	57.58	gold quality
cerebellar vermis	UBERON:0004720	57.52	gold quality
pericardium	UBERON:0002407	57.46	gold quality
dorsal root ganglion	UBERON:0000044	57.29	gold quality
Brodmann (1909) area 46	UBERON:0006483	57.18	gold quality
quadriceps femoris	UBERON:0001377	57.12	gold quality
ventral tegmental area	UBERON:0002691	57.01	gold quality
synovial joint	UBERON:0002217	56.96	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

HPA expression

RNA tissue specificity: Group enriched

showing 60 of 70 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skin 1	tissue	64.1	medium
Vagina	tissue	56.4	low
Esophagus	tissue	39.8	medium
Urinary bladder	tissue	15.7	medium
Salivary gland	tissue	15.6	not detected
Tonsil	tissue	13.6	medium
Breast	tissue	12.8	medium
Placenta	tissue	11.4	low
Stomach 1	tissue	8.3	not detected
Epididymis	tissue	6.6	low
Prostate	tissue	5.9	low
Seminal vesicle	tissue	4.1	low
Cervix	tissue	3.6	low
Gallbladder	tissue	3.5	not detected
Lung	tissue	3.3	not detected
Fallopian tube	tissue	2.7	not detected
Pancreas	tissue	2.2	low
Frontal cortex	tissue	2.2
Rectum	tissue	1.6	not detected
Caudate putamen	tissue	1.5
Colon	tissue	1.4	not detected
Cerebellum	tissue	1.4	not detected
Olfactory bulb	tissue	1.4
Cerebral cortex	tissue	1.3	not detected
Spinal cord	tissue	1.3
Retrosplenial and cingulate cortex	tissue	1.3
Insular cortex	tissue	1.3
Endometrium 1	tissue	1.2	low
Amygdala	tissue	1.2
Corpus callosum	tissue	1.2
Hippocampal formation	tissue	1.2
Entorhinal cortex	tissue	1.2
Retrosplenial cortex	tissue	1.2
Basal ganglia	tissue	1.1	not detected
Ventral forebrain	tissue	1.1
Somatosensory cortex	tissue	1.1
Temporal cortex	tissue	1.1
Occipital cortex	tissue	1.1
Motor cortex	tissue	1.0
Putamen	tissue	1.0
Hypothalamus	tissue	1.0
Prefrontal cortex	tissue	0.9
Nucleus accumbens	tissue	0.9
Choroid plexus	tissue	0.9
Medulla oblongata	tissue	0.9
Kidney	tissue	0.9	low
Periaqueductal gray	tissue	0.9
Septum	tissue	0.9
Midbrain	tissue	0.8
Substantia nigra	tissue	0.8
Locus coeruleus	tissue	0.8
Thymus	tissue	0.8
Postcentral gyrus	tissue	0.8
Duodenum	tissue	0.7	not detected
Hippocampus	tissue	0.7	not detected
Pituitary gland	tissue	0.6
Pons	tissue	0.6
Thalamus	tissue	0.6
Superior colliculi	tissue	0.6
Bone marrow	tissue	0.6	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Anterior thalamic nucleus, ventral (1.5), Corpus callosum, splenium (white matter) (1.3), Flocculonodular lobe (1.3), Parieto-temporal junction (white matter) (1.3), Temporal white matter (1.3).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting NECTIN4 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 59 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 0.864, LOEUF 0.538, missense Z 0.846 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000368012 splits into 3 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
1:161,072,664–161,077,614	364 / 415.7	0.88	no
1:161,077,615–161,079,608	37 / 60.3	0.61	no
1:161,079,609–161,089,296	218 / 186.3	1.17	no

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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1918990) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 4 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased exploration in new environment	1
decreased susceptibility to type I hypersensitivity reaction	1
decreased grip strength	1
preweaning lethality, incomplete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q5E9Z9	88.8%	Diamond
Xenopus laevis	Q66KX2	71.9%	Diamond
Xenopus tropicalis	Q5FWR8	50.3%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
KLHDC9	protein-coding	126823
ARHGAP30	protein-coding	257106
PFDN2	protein-coding	5202
USF1	protein-coding	7391
TSTD1	protein-coding	100131187
NECTIN4-AS1	ncRNA	105371471
NIT1	protein-coding	4817
DEDD	protein-coding	9191

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): K4PZ75, Q96NY8

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 (44 total): strand 16, helix 5, disulfide bond 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 by resolution:

PDB	Title	Method	Resolution (Å)
4JJH	Crystal structure of the D1 domain from human Nectin-4 extracellular fragment …	X-RAY DIFFRACTION	2.25
9UCL	CryoEM structure of IgV domain of human Nectin-4 with Trimbody	ELECTRON MICROSCOPY	2.43
4GJT	complex structure of nectin-4 bound to MV-H	X-RAY DIFFRACTION	3.1
9KKJ	Structure of Nectin-4 D1 domain in complex with the Fab fragment of 9MW2821 mAb	ELECTRON MICROSCOPY	3.26
4FRW	Crystal structure of human nectin-4 extracellular fragment D1-D2	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 antibodies co-crystallized with this protein: 9KKJ

Human Protein Atlas

Protein class: Predicted membrane proteins, Predicted secreted proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of skin

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

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)

Type	Positions
Disulfide bond	52–127, 171–223, 270–315

Glycosylation sites (1)

Type	Positions
N-linked (glcnac…) asparagine	281

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-418990	Adherens junctions interactions	curated
R-HSA-420597	Nectin/Necl trans heterodimerization	curated
R-HSA-446728	Cell junction organization	—
R-HSA-1500931	Cell-Cell communication	—
R-HSA-421270	Cell-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 (4): plasma membrane (GO:0005886), adherens junction (GO:0005912), extracellular exosome (GO:0070062), extracellular region (GO:0005576)

Reactome top-level categories

4 top-level categories:

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

GO top-level categories

26 GO namespaces:

Category	Terms
cell-cell adhesion	2
cellular process	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
cellular anatomical structure	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 15 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
negative regulation of natural killer cell mediated cytotoxicity	BP	direct assay
adherens junction	CC	direct assay
extracellular exosome	CC	high-throughput assay
plasma membrane	CC	direct assay
identical protein binding	MF	physical interaction
receptor ligand activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 630 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NECTIN4	AFDN	P55196	794
NECTIN4	SLAMF1	Q13291	791
NECTIN4	MYBPH	Q13203	719
NECTIN4	TACSTD2	P09758	717
NECTIN4	CD46	P15529	676
NECTIN4	ADAM17	P78536	646
NECTIN4	ERBB2	P04626	498
NECTIN4	CD274	Q9NZQ7	490
NECTIN4	FGFR3	P22607	400
NECTIN4	KLHDC9	Q8NEP7	396
NECTIN4	FOLR1	P15328	388
NECTIN4	PVRIG	Q6DKI7	374
NECTIN4	MSLN	Q13421	370
NECTIN4	SLITRK6	Q9H5Y7	359
NECTIN4	CD226	Q15762	357

IntAct

Human interaction partners of NECTIN4 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

11 partners by confidence:

Partner	Interaction type	MIscore	Records
NECTIN1	direct interaction	0.760	6
H	direct interaction	0.720	4
ZNF582	physical association	0.590	2
DEFB121	physical association	0.560	3
EIF2B2	association	0.530	1
TIGIT	physical association	0.400	2
NECTIN2	physical association	0.400	1
STING1	physical association	0.400	1
AFDN	physical association	0.370	1
EIF2B5	association	0.350	1
GLB1	association	0.350	1

Protein complexes (CORUM) (2)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

2 complexes by size:

Complex	Subunits	Members
★ NECTIN1-NECTIN4 complex	2	NECTIN1, NECTIN4
★ NECTIN4 homodimer	1	NECTIN4

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
NECTIN1	receptor	Adhesion by Nectin

Disease & clinical

Genetic variants

Variant evidence for NECTIN4: 93 ClinVar records (12 pathogenic / likely pathogenic); 3 PharmGKB clinical annotations; 2 GWAS associations. Per-variant detail is on Sugi Variant.

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	11

Top pathogenic / likely-pathogenic (12)

Showing all 12 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
807665	NM_030916.3(NECTIN4):c.229C>T (p.Gln77Ter)	Pathogenic	criteria provided, single submitter	1
996828	NM_030916.3(NECTIN4):c.880C>T (p.Arg294Ter)	Pathogenic	criteria provided, single submitter	1
3613989	NM_030916.3(NECTIN4):c.1117C>T (p.Arg373Ter)	Pathogenic	criteria provided, single submitter	1
4717321	NM_030916.3(NECTIN4):c.242dup (p.Leu82fs)	Pathogenic	criteria provided, single submitter	1
1324796	NM_030916.3(NECTIN4):c.1233+1G>A	Likely pathogenic	criteria provided, single submitter	1
3393124	NM_030916.3(NECTIN4):c.1516C>T (p.Arg506Trp)	Likely pathogenic	criteria provided, single submitter	1
1600	NM_030916.3(NECTIN4):c.851G>A (p.Arg284Gln)	Pathogenic	no assertion criteria provided	1
1601	NM_030916.3(NECTIN4):c.554C>T (p.Thr185Met)	Pathogenic	no assertion criteria provided	1
1602	NM_030916.3(NECTIN4):c.906del (p.Pro304fs)	Pathogenic	no assertion criteria provided	1
30794	NM_030916.3(NECTIN4):c.635C>G (p.Pro212Arg)	Pathogenic	no assertion criteria provided	1
425551	NM_030916.3(NECTIN4):c.724G>A (p.Val242Met)	Pathogenic	no assertion criteria provided	1
425552	NM_030916.3(NECTIN4):c.181C>T (p.Gln61Ter)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore NECTIN4’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 33 predictions of 727):

Position(s)	Effect	Δscore	Sites
1:161073718–161073719	donor_loss	1.0000	5
1:161074216	donor_loss	1.0000
1:161077451–161077452	donor_loss	1.0000	3
1:161077744–161077745	acceptor_loss	1.0000	6
1:161079588–161079589	donor_loss	1.0000	4
1:161079950–161079951	acceptor_loss	1.0000	3
1:161072886–161072887	acceptor_loss	0.9900	4
1:161072895	acceptor_gain	0.9900
1:161073796–161073797	acceptor_loss	0.9900	4
1:161074215–161074216	donor_loss	0.9900	2

AlphaMissense

990 missense substitutions predicted likely pathogenic (of 3,268 scored), across 288 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
F485	8	0.973	0.999
D121	8	0.963	0.992
H227	8	0.946	0.994
F302	8	0.927	0.996
H508	8	0.767	0.918
C171	7	0.999	1.000
C223	7	0.999	1.000
W183	7	0.998	1.000
C315	7	0.997	0.999
C270	7	0.995	0.999
C127	7	0.993	0.999
W282	7	0.992	1.000
C52	7	0.990	0.996
F208	7	0.986	0.999
W67	7	0.979	0.999
R394	7	0.928	0.989
F137	7	0.920	0.983
F132	7	0.915	0.989
F244	7	0.909	0.985
W259	7	0.909	0.997

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Bladder Urothelial Carcinoma)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000301

Disease associations

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

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
ectodermal dysplasia-syndactyly syndrome 1	Definitive	Autosomal recessive	3
ectodermal dysplasia-syndactyly syndrome	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (7 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

7 panels:

Panel	Rating
DDG2P	green
Ectodermal dysplasia	green
Ectodermal dysplasia without a known gene mutation	green
Fetal anomalies	green
Paediatric disorders	green
Amelogenesis imperfecta	amber
Palmoplantar keratodermas	amber

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 phenotypes (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

2 associations:

Study	Trait	p-value
GCST003542_72	Night sleep phenotypes	4e-6
GCST003542_51	Night sleep phenotypes	7e-6

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3712928 (SINGLE PROTEIN)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the NECTIN4 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
ENFORTUMAB VEDOTIN	Antibody drug conjugate	4

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

3 annotations by evidence level (1 strongest → 4):

Variant	Association	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

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

3 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs11265549	methadone	Toxicity	Genotype AA is associated with increased likelihood of Pruritus when treated with methadone in people with Opioid-Related Disorders as compared to genotypes AG + GG.	PMID:32555608
rs11265549	methadone	Dosage	Genotype AA is associated with decreased dose of methadone in people with Opioid-Related Disorders as compared to genotypes AG + GG.	PMID:32555608
rs11265549	methadone	Metabolism/PK	Genotype AA is associated with decreased concentrations of methadone in people with Opioid-Related Disorders as compared to genotypes AG + GG.	PMID:32555608

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

Binding affinities (BindingDB)

50 measured of 56 human assays (56 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5193789	EC50	0.67 nM
CHEMBL5218456	KI	2.4 nM
CHEMBL5220448	KI	2.4 nM
CHEMBL5219064	KD	2.5 nM
CHEMBL5202442	KD	2.8 nM
CHEMBL5218740	KI	2.8 nM
CHEMBL5220463	KI	4.9 nM
CHEMBL5220631	KI	5.2 nM
CHEMBL5220922	KI	6.1 nM
CHEMBL5219136	KI	8.8 nM
CHEMBL5220083	KI	9.7 nM
CHEMBL5219641	KI	12 nM
CHEMBL5221012	KI	13 nM
CHEMBL5220023	KI	13 nM
CHEMBL5202254	EC50	14 nM
CHEMBL5220092	KI	14 nM
CHEMBL5219400	KI	16 nM
CHEMBL5220320	KI	18 nM
CHEMBL5220037	KI	19 nM
CHEMBL5218904	KI	24 nM
CHEMBL5219498	KI	27 nM
CHEMBL5220040	KI	27 nM
CHEMBL5220458	KI	27 nM
CHEMBL5220510	KI	28 nM
CHEMBL5220499	KI	31 nM
CHEMBL5219259	KI	37 nM
CHEMBL5218678	KI	38 nM
CHEMBL5221108	KI	39 nM
CHEMBL5220688	KI	39 nM
CHEMBL5219916	KI	44 nM
CHEMBL5219878	KI	46 nM
CHEMBL5219402	KI	47 nM
CHEMBL5220400	KI	58 nM
CHEMBL5220633	KI	59 nM
CHEMBL5221095	KI	64 nM
CHEMBL5220747	KI	67 nM
CHEMBL5218503	KI	69 nM
CHEMBL5218565	KI	70 nM
CHEMBL5220697	KI	76 nM
CHEMBL5220678	KI	78 nM
CHEMBL5220964	KI	81 nM
CHEMBL5219480	KI	142 nM
CHEMBL5220777	KI	158 nM
CHEMBL5218845	KI	176 nM
CHEMBL5219726	KI	185 nM
CHEMBL5220813	KI	202 nM
CHEMBL5218816	KI	286 nM
CHEMBL5220830	KI	606 nM
CHEMBL5219369	KI	694 nM
CHEMBL5219755	KI	737 nM

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 expression, increases methylation, affects expression	7
Benzo(a)pyrene	decreases methylation, increases expression, increases methylation, decreases expression	6
Particulate Matter	increases abundance, increases expression, affects methylation	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	decreases expression, increases 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	increases expression, affects cotreatment	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 abundance, increases expression	1
cupric chloride	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment	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

7 cell lines: 4 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_F4MQ	HyCyte EMT6 stable cell line for hNECTIN4 overexpression	Cancer cell line	Female
CVCL_RR11	MCF10A PVRL4 (-/-)	Spontaneously immortalized cell line	Female

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for NECTIN4 across ~30M SureChEMBL compounds — explore on Sugi Predict.