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nectin cell adhesion molecule 4

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 3112

Nomenclature: nectin cell adhesion molecule 4

Family: Immunoglobulin C2-set domain-containing proteins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 510 1q23.3 NECTIN4 nectin cell adhesion molecule 4
Previous and Unofficial Names Click here for help
Ig superfamily receptor LNIR | Nectin-4 | Nectin cell adhesion molecule 4 | Poliovirus receptor-related protein 4 | PVRL4
Database Links Click here for help
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Antibodies
Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
enfortumab vedotin Peptide Approved drug Primary target of this compound Hs Binding - - 3
[3]
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
BT7480 Peptide Click here for species-specific activity table Immunopharmacology Ligand Hs Binding 8.3 pKd 4
pKd 8.3 (Kd 5.1x10-9 M) [4]
Description: Binding affinity determined by SPR
Immunopharmacology Comments
Nectin 4 is the target of the immuno-oncology monoclonal antibody enfortumab vedotin, which was FDA approved in 2019 as a therapy for locally advanced/metastatic urothelial cancer that has been previously treated using a PD-1 or PD-L1 immune checkpoint inhibitor and platinum-containing chemotherapy in the neoadjuvant/adjuvant, locally advanced or metastatic setting.
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Ectodermal dysplasia-syndactyly syndrome
Description: A rare autosomal recessive disorder that is characterised by sparse to absent scalp hair, eyebrows, and eyelashes, cutaneous syndactyly and teeth abnormalities.
OMIM: 613573
Orphanet: ORPHA247820
Role: 
References:  1-2
General Comments
Nectin 4 is a surface protein that participates in Ca2+-independent cell-cell adhesion. It is a component of adherens junctions, through interaction with the adaptor protein afadin (AFDN), which links it to the actin cytoskeleton. Nectin 4 is highly expressed in a wide range of solid tumours. The metalloproteinase ADAM17/TACE can cleave nectin 4's extracellular domain to create a secreted form.

References

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1. Brancati F, Fortugno P, Bottillo I, Lopez M, Josselin E, Boudghene-Stambouli O, Agolini E, Bernardini L, Bellacchio E, Iannicelli M et al.. (2010) Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome. Am J Hum Genet, 87 (2): 265-73. [PMID:20691405]

2. Jelani M, Chishti MS, Ahmad W. (2011) Mutation in PVRL4 gene encoding nectin-4 underlies ectodermal-dysplasia-syndactyly syndrome (EDSS1). J Hum Genet, 56 (5): 352-7. [PMID:21346770]

3. McGregor BA, Sonpavde G. (2019) Enfortumab Vedotin, a fully human monoclonal antibody against Nectin 4 conjugated to monomethyl auristatin E for metastatic urothelial Carcinoma. Expert Opin Investig Drugs, 28 (10): 821-826. [PMID:31526130]

4. Upadhyaya P, Kristensson J, Lahdenranta J, Repash E, Ma J, Kublin J, Mudd GE, Luus L, Jeffrey P, Hurov K et al.. (2022) Discovery and Optimization of a Synthetic Class of Nectin-4-Targeted CD137 Agonists for Immuno-oncology. J Med Chem, [Epub ahead of print]. DOI: 10.1021/acs.jmedchem.2c00505 [PMID:35819182]

How to cite this page

Immunoglobulin C2-set domain-containing proteins: nectin cell adhesion molecule 4. Last modified on 13/07/2022. Accessed on 29/11/2022. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=3112.