Target Information

Target General Information

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Target ID

T16340 (Former ID: TTDI01935)

Target Name

Interleukin-1 alpha (IL1A)

Synonyms

IL1F1; IL-1 alpha; Hematopoietin-1

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Gene Name

IL1A

Target Type

Clinical trial target

[1]

Disease

[+] 2 Target-related Diseases

Colorectal cancer [ICD-11: 2B91]

Influenza [ICD-11: 1E30-1E32]

Function

Produced by activated macrophages, IL-1 stimulates thymocyte proliferation by inducing IL-2 release, B-cell maturation and proliferation, and fibroblast growth factor activity. IL-1 proteins are involved in the inflammatory response, being identified as endogenous pyrogens, and are reported to stimulate the release of prostaglandin and collagenase from synovial cells.

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BioChemical Class

Cytokine: interleukin

UniProt ID

IL1A_HUMAN

Sequence

MAKVPDMFEDLKNCYSENEEDSSSIDHLSLNQKSFYHVSYGPLHEGCMDQSVSLSISETS
KTSKLTFKESMVVVATNGKVLKKRRLSLSQSITDDDLEAIANDSEEEIIKPRSAPFSFLS
NVKYNFMRIIKYEFILNDALNQSIIRANDQYLTAAALHNLDEAVKFDMGAYKSSKDDAKI
TVILRISKTQLYVTAQDEDQPVLLKEMPEIPKTITGSETNLLFFWETHGTKNYFTSVAHP
NLFIATKQDYWVCLAGGPPSITDFQILENQA

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3D Structure

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AlphaFold

ADReCS ID

BADD_A00752 ; BADD_A03065 ; BADD_A05322 ; BADD_A05823

HIT2.0 ID

T34HYH

Drugs and Modes of Action

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Clinical Trial Drug(s)

[+] 5 Clinical Trial Drugs

MABp1

Drug Info

Phase 3

Colorectal cancer

[2]

Xilonix

Drug Info

Phase 3

Influenza virus infection

[3]

ABT-981

Drug Info

Phase 2

Osteoarthritis

[4], [5]

Bermekimab

Drug Info

Phase 2

Hidradenitis suppurativa

[6]

Natrunix

Drug Info

Phase 2

Arthritis

[7]

Discontinued Drug(s)

[+] 2 Discontinued Drugs

IX207-887

Drug Info

Discontinued in Phase 2

Rheumatoid arthritis

[8]

IL1aQb

Drug Info

Terminated

Arteriosclerosis

[9]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 2 Inhibitor drugs

MABp1

Drug Info

[10]

Natrunix

Drug Info

[7]

Modulator

[+] 4 Modulator drugs

Xilonix

Drug Info

[11]

ABT-981

Drug Info

[1]

IX207-887

Drug Info

[13], [14]

Interleukin-1-alpha - Amgen/Roche

Drug Info

[16]

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
MAPK signaling pathway	hsa04010	Affiliated Target
Class: Environmental Information Processing => Signal transduction	Pathway Hierarchy
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
Cellular senescence	hsa04218	Affiliated Target
Class: Cellular Processes => Cell growth and death	Pathway Hierarchy
Osteoclast differentiation	hsa04380	Affiliated Target
Class: Organismal Systems => Development and regeneration	Pathway Hierarchy
Hematopoietic cell lineage	hsa04640	Affiliated Target
Class: Organismal Systems => Immune system	Pathway Hierarchy
Click to Show/Hide the Information of Affiliated Human Pathways

Degree	27	Degree centrality	2.90E-03	Betweenness centrality	3.72E-04
Closeness centrality	2.29E-01	Radiality	1.40E+01	Clustering coefficient	4.50E-01
Neighborhood connectivity	2.90E+01	Topological coefficient	9.51E-02	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	[+] 17 KEGG Pathways	+
1	MAPK signaling pathway
2	Cytokine-cytokine receptor interaction
3	Apoptosis
4	Osteoclast differentiation
5	Hematopoietic cell lineage
6	Non-alcoholic fatty liver disease (NAFLD)
7	Type I diabetes mellitus
8	Prion diseases
9	Salmonella infection
10	Pertussis
11	Leishmaniasis
12	Tuberculosis
13	Measles
14	Influenza A
15	Inflammatory bowel disease (IBD)
16	Rheumatoid arthritis
17	Graft-versus-host disease
NetPath Pathway	[+] 3 NetPath Pathways	+
1	IL5 Signaling Pathway
2	IL1 Signaling Pathway
3	TCR Signaling Pathway
Panther Pathway	[+] 1 Panther Pathways	+
1	Interleukin signaling pathway
PID Pathway	[+] 3 PID Pathways	+
1	IL1-mediated signaling events
2	Validated transcriptional targets of deltaNp63 isoforms
3	a6b1 and a6b4 Integrin signaling
Reactome	[+] 3 Reactome Pathways	+
1	Senescence-Associated Secretory Phenotype (SASP)
2	Interleukin-1 signaling
3	Interleukin-1 processing
WikiPathways	[+] 13 WikiPathways	+
1	SIDS Susceptibility Pathways
2	TCR Signaling Pathway
3	Senescence and Autophagy in Cancer
4	Cytokines and Inflammatory Response
5	Hypertrophy Model
6	MAPK Signaling Pathway
7	FAS pathway and Stress induction of HSP regulation
8	Hematopoietic Stem Cell Differentiation
9	Structural Pathway of Interleukin 1 (IL-1)
10	Spinal Cord Injury
11	Allograft Rejection
12	IL-1 signaling pathway
13	Interleukin-1 signaling

References

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REF 1

Generation and characterization of ABT-981, a dual variable domain immunoglobulin (DVD-Ig(TM)) molecule that specifically and potently neutralizes both IL-1alpha and IL-1beta. MAbs. 2015;7(3):605-19.

REF 2

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

REF 3

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

REF 4

ClinicalTrials.gov (NCT02087904) A Phase 2a Study Evaluating the Safety, Efficacy, and Pharmacodynamic Effects of ABT-981 in Patients With Knee Osteoarthritis

REF 5

ClinicalTrials.gov (NCT02384538) A Phase 2a Study Evaluating the Safety and Efficacy of ABT-981 in Patients With Erosive Hand Osteoarthritis

REF 6

ClinicalTrials.gov (NCT03512275) A Phase II, Open Label Study of Bermekimab in Patients With Moderate to Severe Hidradenitis Suppurativa. U.S.National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT05363917) Phase II Double-Blinded, Placebo-Controlled Randomized Study Examining the Safety and Efficacy of Natrunix Versus Methotrexate (+Folate) for the Treatment of Rheumatoid Arthritis. U.S.National Institutes of Health.

REF 8

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002363)

REF 9

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800021743)

REF 10

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

REF 11

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

REF 12

Target molecules for future hidradenitis suppurativa treatment. Exp Dermatol. 2021 Jun;30 Suppl 1:8-17.

REF 13

Inhibition of interleukin-1 release by IX 207-887. Agents Actions. 1990 Jun;30(3-4):350-62.

REF 14

Modulation of secretory processes of phagocytes by IX 207-887. Springer Semin Immunopathol. 1993;14(4):345-52.

REF 15

Cytos Biotechnology AG - Product Pipeline Review - 2013. Global Markets Direct. Dec 2013.

REF 16

Identification of regions in interleukin-1 alpha important for activity. J Biol Chem. 1993 Oct 15;268(29):22105-11.

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