Target Information

Target General Information

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Target ID

T65883 (Former ID: TTDI02045)

Target Name

Claudin-18 (CLDN18)

Synonyms

UNQ778/PRO1572; Claudin18

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Gene Name

CLDN18

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Oesophagogastric junction cancer [ICD-11: 2B71]

Stomach cancer [ICD-11: 2B72]

Function

Plays a major role in tight junction-specific obliteration of the intercellular space, through calcium-independent cell-adhesion activity.

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UniProt ID

CLD18_HUMAN

Sequence

MSTTTCQVVAFLLSILGLAGCIAATGMDMWSTQDLYDNPVTSVFQYEGLWRSCVRQSSGF
TECRPYFTILGLPAMLQAVRALMIVGIVLGAIGLLVSIFALKCIRIGSMEDSAKANMTLT
SGIMFIVSGLCAIAGVSVFANMLVTNFWMSTANMYTGMGGMVQTVQTRYTFGAALFVGWV
AGGLTLIGGVMMCIACRGLAPEETNYKAVSYHASGHSVAYKPGGFKASTGFGSNTKNKKI
YDGGARTEDEVQSYPSKHDYV

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3D Structure

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AlphaFold

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 9 Clinical Trial Drugs

Claudiximab

Drug Info

Phase 3

Gastric adenocarcinoma

[2]

Zolbetuximab

Drug Info

Phase 3

Gastric adenocarcinoma

[3]

CT-041

Drug Info

Phase 1/2

Gastric cancer

[4]

RC118

Drug Info

Phase 1/2

Aggressive cancer

[5]

AMG 910

Drug Info

Phase 1

Gastric adenocarcinoma

[6]

ASP2138

Drug Info

Phase 1

Stomach cancer

[7]

SKB315

Drug Info

Phase 1

Aggressive cancer

[8]

TST001

Drug Info

Phase 1

Solid tumour/cancer

[9]

CAR-CLD18 T cell

Drug Info

Clinical trial

Adenocarcinoma

[10]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

BNT212

Drug Info

Preclinical

Aggressive cancer

[11]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

AMG 910

Drug Info

[14]

CAR-T-Cell-Therapy

[+] 1 CAR-T-Cell-Therapy drugs

CAR-CLD18 T cell

Drug Info

[10]

Cell-based Target Expression Variations

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Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation

Different Human System Profiles of Target

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Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Cell adhesion molecules	hsa04514	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Tight junction	hsa04530	Affiliated Target
Class: Cellular Processes => Cellular community - eukaryotes	Pathway Hierarchy
Leukocyte transendothelial migration	hsa04670	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Target Regulators

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Target-regulating microRNAs

Target-regulating microRNAs Info

Target Profiles in Patients

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Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

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KEGG Pathway

[+] 4 KEGG Pathways

Cell adhesion molecules (CAMs)

Tight junction

Leukocyte transendothelial migration

Hepatitis C

NetPath Pathway

[+] 1 NetPath Pathways

IL4 Signaling Pathway

Reactome

[+] 1 Reactome Pathways

Tight junction interactions

References

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REF 1

Claudin 18.2 is a target for IMAB362 antibody in pancreatic neoplasms. Int J Cancer. 2014 Feb 1;134(3):731-9.

REF 2

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 3

ClinicalTrials.gov (NCT03504397) A Phase 3 Efficacy, Safety and Tolerability Study of Zolbetuximab (Experimental Drug) Plus mFOLFOX6 Chemotherapy Compared to Placebo Plus mFOLFOX6 as Treatment for Gastric and Gastroesophageal Junction (GEJ) Cancer (Spotlight). U.S. National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT04404595) Open-label, Multicenter, Phase 1b/2 Clinical Trial to Evaluate the Safety and Efficacy of Autologous Anti-claudin 18.2 Chimeric Antigen Receptor T-cell Therapy in Subjects With Advanced Gastric, Pancreatic, or Other Specified Digestive System Cancers. U.S.National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT05205850) An Open, Multi-center Phase I/IIa Clinical Study of RC118 for Injection in Patients With Locally Advanced Unresectable or Metastatic Malignant Solid Tumors With Positive Expression of Claudin 18.2. U.S.National Institutes of Health.

REF 6

ClinicalTrials.gov (NCT04260191) Study of AMG 910 in Subjects With CLDN18.2-Positive Gastric and Gastroesophageal Junction Adenocarcinoma. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT05365581) A Phase 1/1b Study of ASP2138 in Participants With Metastatic or Locally Advanced Unresectable Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma or Metastatic Pancreatic Adenocarcinoma Whose Tumors Have Claudin (CLDN) 18.2 Expression. U.S.National Institutes of Health.

REF 8

ClinicalTrials.gov (NCT05367635) A Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of SKB315 for Injection in Patients With Advanced Solid Tumors Expressing Claudin18.2. U.S.National Institutes of Health.

REF 9

ClinicalTrials.gov (NCT04495296) A Trial to Evaluate Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of TST001 in Advanced or Metastatic Solid Tumors. U.S. National Institutes of Health.

REF 10

ClinicalTrials.gov (NCT03302403) Clinical Study of Redirected Autologous T Cells With a Chimeric Antigen Receptor in Patients With Malignant Tumors

REF 11

Clinical pipeline report, company report or official report of Biontech

REF 12

FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021 May;32(5):609-619.

REF 13

Clinical pipeline report, company report or official report of CARSGEN

REF 14

Clinical pipeline report, company report or official report of Amgen.

REF 15

Clinical pipeline report, company report or official report of Klus Pharma

REF 16

Clinical pipeline report, company report or official report of Transcenta.

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