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claudin 18

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 2903

Nomenclature: claudin 18

Family: Claudins

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 4 261 3q22.3 CLDN18 claudin 18
Mouse 4 264 9 E3.3 Cldn18 claudin 18
Rat - 261 8q31 Cldn18 claudin 18
Previous and Unofficial Names Click here for help
surfactant associated protein J | SFTPJ
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
zolbetuximab Peptide Primary target of this compound Hs Binding - - 1
[1]
ZWB67 Peptide Click here for species-specific activity table Hs Binding - - 4
[4]
Description: EC50 ~2 μg/mL in cells expressing CLDN18.2
Antibody Comments
NOTE: to date the antibodies that target CLDN18 are designed to bind ONLY to the CLDN18.2 splice variant.
A clinical candidate in this class of agents is Amgen's bispecific CLDN18.2/CD3e gresonitamab (AMG910; Phase 1 NCT04260191), although there is nothing in the peer reviewed literature about this antibody. An anti-CLDN18.2 ADC was disclosed during the 'First Disclosures of New Drug Candidates' session at the April 2023 (Orlando) meeting of the AACR: EO-3021 (SYS1810), from Elevation Oncology, is loaded with the microtubule disrupting, antimitotic agent monomethyl auristatin E (MMAE; vedotin when linked to a mAb).
Immunopharmacology Comments
Claudin-18.1 is expressed exclusively in the tight junctions of lung epithelia. Claudin-18 deficiency has been identified as a contributor to airway epithelial barrier dysfunction and asthmatic reactions to air-borne antigens [3].
Immuno Process Associations
Immuno Process:  Immune regulation
Immuno Process:  Immune system development
Immuno Process:  Cytokine production & signalling
Biologically Significant Variants Click here for help
Type:  Splice variant
Species:  Human
Description:  CLDN18, transcript variant 2 has an alternate 5' exon, as compared to variant 1. The encoded protein, isoform 2 (CLDN18.2) is the same length as isoform 1, but has a different N-terminus.
Amino acids:  261
Nucleotide accession: 
Protein accession: 
General Comments
CLDN18 is a member of the claudins family of integral membrane proteins. Claudins are components of tight junction strands which serve as a physical barrier between epithelial or endothelial cell sheets. Alternatively spliced transcript variants encoding different protein isoforms have been identified in human and mouse.

In normal human tissue the splice variant CLDN18.2 is expressed exclusively on short-lived differentiated gastric epithelial cells, so is therefore a highly selective surface marker of gastric lineage. Expression of CLDN18.2 is maintained through malignant transformation and hence, is frequently displayed on the surface of human gastric cancer cells. It is also found ectopically expressed in esophageal, pancreatic and lung adenocarcinomas. The limited expression of CLDN18.2 makes it a favourable target for immunotherapy based drug development, and it is being investigated as a target for gastrointestinal, and other cancers in which it is expressed. Zolbetuximab (IMAB362) is a first-in-class anti-CLDN18.2 therapeutic candidate [2].

References

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1. Sahin U, Koslowski M, Dhaene K, Usener D, Brandenburg G, Seitz G, Huber C, Türeci O. (2008) Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res, 14 (23): 7624-34. [PMID:19047087]

2. Sahin U, Tureci O. (2014) Therapy involving antibodies against claudin 18.2 for treatment of cancer. Patent number: WO2014146778. Assignee: Ganymed Pharmaceuticals Ag. Priority date: 18/03/2013. Publication date: 25/09/2014.

3. Sweerus K, Lachowicz-Scroggins M, Gordon E, LaFemina M, Huang X, Parikh M, Kanegai C, Fahy JV, Frank JA. (2017) Claudin-18 deficiency is associated with airway epithelial barrier dysfunction and asthma. J Allergy Clin Immunol, 139 (1): 72-81.e1. [PMID:27215490]

4. Xu G, Qian N, Liu Y, Li H, Yang C, Wang J, Wang F, Chen L, Bai G, Xu Q et al.. (2022) Preclinical characterization of a Fab-like CD3/CLDN18.2 XFab® bispecific antibody against solid tumors. Immunobiology, 227 (6): 152283. [PMID:36198215]

How to cite this page

Claudins: claudin 18. Last modified on 20/04/2023. Accessed on 25/04/2024. IUPHAR/BPS Guide to PHARMACOLOGY, https://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=2903.