Target Information

Target General Information

Target ID

T23797 (Former ID: TTDI02101)

Target Name

Interleukin-33 (IL33)

Synonyms

Nuclear factor from high endothelial venules; NFHEV; NF-HEV; Interleukin1 family member 11; Interleukin-1 family member 11; IL1F11; IL-33; IL-1F11; C9orf26

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Gene Name

IL33

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Chronic obstructive pulmonary disease [ICD-11: CA22]

Respiratory failure ICD-11: CB41

Function

Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury. Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.

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BioChemical Class

Cytokine: interleukin

UniProt ID

IL33_HUMAN

Sequence

MKPKMKYSTNKISTAKWKNTASKALCFKLGKSQQKAKEVCPMYFMKLRSGLMIKKEACYF
RRETTKRPSLKTGRKHKRHLVLAACQQQSTVECFAFGISGVQKYTRALHDSSITGISPIT
EYLASLSTYNDQSITFALEDESYEIYVEDLKKDEKKDKVLLSYYESQHPSNESGDGVDGK
MLMVTLSPTKDFWLHANNKEHSVELHKCEKPLPDQAFFVLHNMHSNCVSFECKTDPGVFI
GVKDNHLALIKVDSSENLCTENILFKLSET

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3D Structure

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AlphaFold

HIT2.0 ID

T03TJ0

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 6 Clinical Trial Drugs

Itepekimab

Drug Info

Phase 3

Chronic obstructive pulmonary disease

[2]

MEDI3506

Drug Info

Phase 3

Chronic obstructive pulmonary disease

[3]

SAR440340

Drug Info

Phase 3

Chronic obstructive pulmonary disease

[2]

Tozorakimab

Drug Info

Phase 3

Chronic obstructive pulmonary disease

[3]

AMG 282

Drug Info

Phase 1

Asthma

[4]

PF-07264660

Drug Info

Phase 1

Atopic dermatitis

[5]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

Tozorakimab

Drug Info

[7]

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). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

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).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

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
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
Necroptosis	hsa04217	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Cytosolic DNA-sensing pathway	hsa04623	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	4	Degree centrality	4.30E-04	Betweenness centrality	2.12E-04
Closeness centrality	2.01E-01	Radiality	1.35E+01	Clustering coefficient	0.00E+00
Neighborhood connectivity	1.83E+01	Topological coefficient	2.54E-01	Eccentricity	12
Download	Click to Download the Full PPI Network of This Target

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

[+] 2 KEGG Pathways

Cytosolic DNA-sensing pathway

Influenza A

References

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REF 1

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

REF 2

ClinicalTrials.gov (NCT04701983) Randomized, Double-blind, Placebo-controlled, Parallel Group Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of SAR440340/REGN3500/Itepekimab (Anti-IL-33 mAb) in Patients With Moderate-to-severe Chronic Obstructive Pulmonary Disease (COPD). U.S.National Institutes of Health.

REF 3

ClinicalTrials.gov (NCT05742802) A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Extension Study to Evaluate the Long-term Efficacy and Safety of Tozorakimab (MEDI3506) in Participants With Chronic Obstructive Pulmonary Disease (COPD) With a History of Exacerbations. U.S.National Institutes of Health.

REF 4

ClinicalTrials.gov (NCT02170337) A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AMG 282 in Healthy Subjects and Subjects With Chronic Rhinosinusitis With Nasal Polyps. U.S. National Institutes of Health.

REF 5

ClinicalTrials.gov (NCT05496738) A PHASE 1, RANDOMIZED, DOUBLE-BLIND, SPONSOR-OPEN, PLACEBO-CONTROLLED, DOSE-ESCALATING STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF SINGLE AND MULTIPLE INTRAVENOUS AND SUBCUTANEOUS DOSES OF PF-07264660 IN HEALTHY PARTICIPANTS. U.S.National Institutes of Health.

REF 6

Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. N Engl J Med. 2021 Oct 28;385(18):1656-1668.

REF 7

ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jul 31;21(1):691.

REF 8

Clinical pipeline report, company report or official report of Pfizer

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