Target Information

Target General Information

Target ID

T06841 (Former ID: TTDI01808)

Target Name

Interleukin-23 (IL23)

Synonyms

UNQ2498/PRO5798; SGRF; P40 subunit of interleukin-23; Interleukin-23 subunit p19; Interleukin-23 subunit alpha; Interleukin 23 subunit alpha; IL-23p19; IL-23-A; IL-23 subunit alpha; IL-23

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Gene Name

IL23A

Target Type

Successful target

[1]

Disease

[+] 1 Target-related Diseases

Psoriasis [ICD-11: EA90]

Function

IL-23 may constitute with IL-17 an acute response to infection in peripheral tissues. IL-23 binds to a heterodimeric receptor complex composed of IL12RB1 and IL23R, activates the Jak-Stat signaling cascade, stimulates memory rather than naive T-cells and promotes production of proinflammatory cytokines. IL-23 induces autoimmune inflammation and thus may be responsible for autoimmune inflammatory diseases and may be important for tumorigenesis. Associates with IL12B to form the IL-23 interleukin, a heterodimeric cytokine which functions in innate and adaptive immunity.

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BioChemical Class

Cytokine: interleukin

UniProt ID

IL23A_HUMAN

Sequence

MLGSRAVMLLLLLPWTAQGRAVPGGSSPAWTQCQQLSQKLCTLAWSAHPLVGHMDLREEG
DEETTNDVPHIQCGDGCDPQGLRDNSQFCLQRIHQGLIFYEKLLGSDIFTGEPSLLPDSP
VGQLHASLLGLSQLLQPEGHHWETQQIPSLSPSQPWQRLLLRFKILRSLQAFVAVAARVF
AHGAATLSP

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3D Structure

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PDB

HIT2.0 ID

T51AX1

Drugs and Modes of Action

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Approved Drug(s)

[+] 4 Approved Drugs

CNTO-1959

Drug Info

Approved

Plaque psoriasis

[2]

Risankizumab

Drug Info

Approved

Plaque psoriasis

[3]

Tildrakizumab

Drug Info

Approved

Plaque psoriasis

[4]

Ustekinumab

Drug Info

Approved

Plaque psoriasis

[5], [6]

Clinical Trial Drug(s)

[+] 4 Clinical Trial Drugs

BI 655066

Drug Info

Phase 3

Chronic plaque psoriasis

[9]

MK-3222

Drug Info

Phase 3

Psoriasis vulgaris

[10], [11]

CNT0-1959

Drug Info

Phase 2

Rheumatoid arthritis

[12]

AMG-139

Drug Info

Phase 1

Crohn disease

[14]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 1 Inhibitor drugs

Risankizumab

Drug Info

[3]

Modulator

[+] 1 Modulator drugs

Tildrakizumab

Drug Info

[4]

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 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 Pathway Affiliation Biological Network Descriptors

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 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 Pathway Affiliation

Biological Network Descriptors

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

KEGG Pathway	Pathway ID	Affiliated Target
Cytokine-cytokine receptor interaction	hsa04060	Affiliated Target
Class: Environmental Information Processing => Signaling molecules and interaction	Pathway Hierarchy
C-type lectin receptor signaling pathway	hsa04625	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
JAK-STAT signaling pathway	hsa04630	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
Th17 cell differentiation	hsa04659	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy

Degree	8	Degree centrality	8.59E-04	Betweenness centrality	7.75E-06
Closeness centrality	2.19E-01	Radiality	1.38E+01	Clustering coefficient	6.07E-01
Neighborhood connectivity	3.71E+01	Topological coefficient	2.13E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

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		Top
KEGG Pathway	[+] 19 KEGG Pathways	+
1	Cytokine-cytokine receptor interaction
2	Toll-like receptor signaling pathway
3	RIG-I-like receptor signaling pathway
4	Jak-STAT signaling pathway
5	Type I diabetes mellitus
6	Pertussis
7	Legionellosis
8	Leishmaniasis
9	Chagas disease (American trypanosomiasis)
10	African trypanosomiasis
11	Malaria
12	Toxoplasmosis
13	Amoebiasis
14	Tuberculosis
15	Measles
16	Influenza A
17	Herpes simplex infection
18	Inflammatory bowel disease (IBD)
19	Allograft rejection
WikiPathways	[+] 4 WikiPathways	+
1	Toll-like receptor signaling pathway
2	Aryl Hydrocarbon Receptor Pathway
3	Allograft Rejection
4	Regulation of toll-like receptor signaling pathway

References

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REF 1

Interleukin-23 in the pathogenesis and treatment of psoriasis. Skin Therapy Lett. 2015 Mar-Apr;20(2):1-4.

REF 2

2017 FDA drug approvals.Nat Rev Drug Discov. 2018 Feb;17(2):81-85.

REF 3

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019

REF 4

2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.

REF 5

URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6885).

REF 6

Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.

REF 7

ClinicalTrials.gov (NCT03961815) An Open-label, Long-term Extension Study of Brazikumab in Participants With Moderately to Severely Active Crohn's Disease (INTREPID OLE). U.S.National Institutes of Health.

REF 8

ClinicalTrials.gov (NCT04607980) A Phase 3, Multicenter, Randomized, Double-Blind Study Evaluating the Efficacy and Safety of ABP 654 Compared With Ustekinumab in Subjects With Moderate to Severe Plaque Psoriasis. U.S.National Institutes of Health.

REF 9

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

REF 10

REF 11

ClinicalTrials.gov (NCT01936688) A Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous MK-3222 in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-012). U.S. National Institutes of Health.

REF 12

Anti-Interleukin-23 Monoclonal Antibody Guselkumab Shows Significant Efficacy in Treatment of Moderate to Severe Plaque Psoriasis. Janssen Research & Development, LLC (Janssen). Mar 24, 2014.

REF 13

ClinicalTrials.gov (NCT03739931) Dose Escalation Study of mRNA-2752 for Intratumoral Injection to Participants With Advanced Malignancies. U.S. National Institutes of Health.

REF 14

ClinicalTrials.gov (NCT01258205) Multiple Ascending Doses of AMG 139 in Healthy and Crohn's Disease Subjects. U.S. National Institutes of Health.

REF 15

Emerging drugs for psoriasis. Expert Opin Emerg Drugs. 2009 Mar;14(1):145-63.

REF 16

Emerging drugs to treat Crohn's disease. Expert Opin Emerg Drugs. 2007 Mar;12(1):49-59.

REF 17

Anti-IL-23A mAb BI 655066 for treatment of moderate-to-severe psoriasis: Safety, efficacy, pharmacokinetics, and biomarker results of a single-rising-dose, randomized, double-blind, placebo-controlled trial. J Allergy Clin Immunol. 2015 Jul;136(1):116-124.e7.

REF 18

Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9.

REF 19

Preclinical development of AMG 139, a human antibody specifically targeting IL-23. Br J Pharmacol. 2015 Jan;172(1):159-72.

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