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Target Overview
Claudin 18 is a transmembrane protein and is an important component of the tight junction complexes that regulate cell-cell adhesion, cell permeability, and cell polarity. Alternative splicing of Claudin 18 transcripts results in 2 isoforms: CLDN18.1, which is expressed in the lung and CLDN18.2, which is restricted to the gastric epithelium. In normal tissues, CLDN18.2 expression is restricted to the gastric mucosa. In tumor tissues, CLDN18.2 is widely overexpressed in a variety of cancers such as GC, GEJC, PDAC, and adenocarcinoma of esophagus and is a validated therapeutic target.1-4
Compound Overview
AZD4360 is an ADC that targets CLDN18.2, consisting of a human IgG1κ anti-CLDN18.2 antibody that is conjugated to a warhead with a drug-antibody ratio of 4. By targeting CLDN18.2-positive cancer cells, AZD4360 is internalized and releases its payload that leads to programmed cell death. The payload can also diffuse to neighboring cancer cells lacking CLDN18.2, enabling a bystander killing effect.
Mechanism of Action
References
1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634. 2. Shitara K, Lordick F, Bang Y-J, et al. Lancet. 2023;401(10389):1655-1668. 3. Shah MA, Shitara K, Ajani JA, et al. Nat Med. 2023;29(8):2133-2141. 4. Ruan DY, Liu FR, Wei XL, et al. Lancet Oncol. 2025;26(2):227-238.
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Abbreviations
CLDN18.2
Claudin 18 isoform 2
GC
gastric cancer
GEJC
gastroesophageal junction cancer
PDAC
pancreatic ductal adenocarcinoma
TOP1i
topoisomerase 1 inhibitor
Target Overview
Claudin 18 is a transmembrane protein and is an important component of the tight junction complexes that regulate cell-cell adhesion, cell permeability, and cell polarity. Alternative splicing of Claudin 18 transcripts results in 2 isoforms: CLDN18.1, which is expressed in the lung and CLDN18.2, which is restricted to the gastric epithelium. In normal tissues, CLDN18.2 expression is restricted to the gastric mucosa. In tumor tissues, CLDN18.2 is widely overexpressed in a variety of cancers such as GC, GEJC, PDAC, and adenocarcinoma of esophagus and is a validated therapeutic target.1-4
Compound Overview
AZD4360 is an ADC that targets CLDN18.2, consisting of a human IgG1κ anti-CLDN18.2 antibody that is conjugated to a warhead with a drug-antibody ratio of 4. By targeting CLDN18.2-positive cancer cells, AZD4360 is internalized and releases its payload that leads to programmed cell death. The payload can also diffuse to neighboring cancer cells lacking CLDN18.2, enabling a bystander killing effect.
Mechanism of Action
References
1. Sahin U, Koslowski M, Dhaene K, et al. Clin Cancer Res. 2008;14(23):7624-7634. 2. Shitara K, Lordick F, Bang Y-J, et al. Lancet. 2023;401(10389):1655-1668. 3. Shah MA, Shitara K, Ajani JA, et al. Nat Med. 2023;29(8):2133-2141. 4. Ruan DY, Liu FR, Wei XL, et al. Lancet Oncol. 2025;26(2):227-238.
Clinical trial information
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Abbreviations
CLDN18.2
Claudin 18 isoform 2
GC
gastric cancer
GEJC
gastroesophageal junction cancer
PDAC
pancreatic ductal adenocarcinoma
TOP1i
topoisomerase 1 inhibitor