Target Information

Target General Information

Target ID

T13251 (Former ID: TTDC00033)

Target Name

Interleukin-12 alpha (IL12A)

Synonyms

NKSF1; NKSF; NK cell stimulatory factor chain 1; NK cell stimulatory factor; Interleukin-12 subunit alpha; IL-12A; IL-12 subunit p35; IL-12; Cytotoxic lymphocyte maturation factor 35 kDa subunit; CLMF p35

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Gene Name

IL12A

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Psoriasis [ICD-11: EA90]

Ulcerative colitis [ICD-11: DD71]

Function

Cytokine that can act as a growth factor for activated T and NK cells, enhance the lytic activity of NK/lymphokine-activated killer cells, and stimulate the production of IFN-gamma by resting PBMC.

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BioChemical Class

Cytokine: interleukin

UniProt ID

IL12A_HUMAN

Sequence

MCPARSLLLVATLVLLDHLSLARNLPVATPDPGMFPCLHHSQNLLRAVSNMLQKARQTLE
FYPCTSEEIDHEDITKDKTSTVEACLPLELTKNESCLNSRETSFITNGSCLASRKTSFMM
ALCLSSIYEDLKMYQVEFKTMNAKLLMDPKRQIFLDQNMLAVIDELMQALNFNSETVPQK
SSLEEPDFYKTKIKLCILLHAFRIRAVTIDRVMSYLNAS

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3D Structure

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PDB

Drugs and Modes of Action

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Approved Drug(s)

[+] 2 Approved Drugs

Mirikizumab

Drug Info

Approved

Ulcerative colitis

[2]

Ustekinumab

Drug Info

Approved

Plaque psoriasis

[1], [3]

Clinical Trial Drug(s)

[+] 1 Clinical Trial Drugs

STA-5326

Drug Info

Phase 2

Rheumatoid arthritis

[4], [5]

Mode of Action

[+] 1 Modes of Action

Inhibitor

[+] 2 Inhibitor drugs

Mirikizumab

Drug Info

[2]

STA-5326

Drug Info

[8], [9]

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

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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 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
Toll-like receptor signaling pathway	hsa04620	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
RIG-I-like receptor signaling pathway	hsa04622	Affiliated Target
Class: Organismal Systems => Immune system	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
Th1 and Th2 cell differentiation	hsa04658	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
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Degree	4	Degree centrality	4.30E-04	Betweenness centrality	1.60E-05
Closeness centrality	1.93E-01	Radiality	1.33E+01	Clustering coefficient	3.33E-01
Neighborhood connectivity	1.95E+01	Topological coefficient	2.96E-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
PID Pathway	[+] 2 PID Pathways	+
1	IL27-mediated signaling events
2	IL12-mediated signaling events
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

Target-Related Models and Studies

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Target Validation

Target Validation Info

References

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REF 1

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

REF 2

FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 761279

REF 3

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 4

A phase 1/2A trial of STA 5326, an oral interleukin-12/23 inhibitor, in patients with active moderate to severe Crohn's disease. Inflamm Bowel Dis. 2006 Jul;12(7):558-65.

REF 5

Emerging drugs for moderate-to-severe psoriasis. Expert Opin Emerg Drugs. 2005 Feb;10(1):35-52.

REF 6

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

REF 7

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

REF 8

Therapeutic effect of the potent IL-12/IL-23 inhibitor STA-5326 on experimental autoimmune uveoretinitis. Arthritis Res Ther. 2008;10(5):R122.

REF 9

Selective abrogation of Th1 response by STA-5326, a potent IL-12/IL-23 inhibitor. Blood. 2007 Feb 1;109(3):1156-64.

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