Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTPM6HI)

• DTT Name: Interleukin-1 alpha (IL1A)
• Synonyms: IL1F1; IL-1 alpha; Hematopoietin-1
• Gene Name: IL1A
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL1A_HUMAN
• TTD ID: T16340
• Sequence:
  MAKVPDMFEDLKNCYSENEEDSSSIDHLSLNQKSFYHVSYGPLHEGCMDQSVSLSISETS
  KTSKLTFKESMVVVATNGKVLKKRRLSLSQSITDDDLEAIANDSEEEIIKPRSAPFSFLS
  NVKYNFMRIIKYEFILNDALNQSIIRANDQYLTAAALHNLDEAVKFDMGAYKSSKDDAKI
  TVILRISKTQLYVTAQDEDQPVLLKEMPEIPKTITGSETNLLFFWETHGTKNYFTSVAHP
  NLFIATKQDYWVCLAGGPPSITDFQILENQA
• 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.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Cytokine-cytokine receptor interaction (hsa04060)
  Apoptosis (hsa04210)
  Osteoclast differentiation (hsa04380)
  Hematopoietic cell lineage (hsa04640)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Type I diabetes mellitus (hsa04940)
  Prion diseases (hsa05020)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Leishmaniasis (hsa05140)
  Tuberculosis (hsa05152)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Inflammatory bowel disease (IBD) (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Graft-versus-host disease (hsa05332)
• Reactome Pathway:
  Interleukin-1 signaling (R-HSA-446652)
  Interleukin-1 processing (R-HSA-448706)
  Senescence-Associated Secretory Phenotype (SASP) (R-HSA-2559582)

Molecular Interaction Atlas (MIA) of This DTT

5 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
MABp1	DM8D13S	Colorectal cancer	2B91.Z	Phase 3	[2]
Xilonix	DMK34MZ	Colorectal cancer	2B91.Z	Phase 3	[3]
ABT-981	DM6PTIX	Osteoarthritis	FA00-FA05	Phase 2	[1]
Bermekimab	DM7A592	Hidradenitis suppurativa	ED92.0	Phase 2	[4]
Natrunix	DMBRSWJ	Arthritis	FA20	Phase 2	[5]

2 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
IX207-887	DM4TE8R	Rheumatoid arthritis	FA20	Discontinued in Phase 2	[6]
IL1aQb	DMKS4Z9	Arteriosclerosis	BD40	Terminated	[7]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Interleukin-1-alpha - Amgen/Roche	DMB9AIX	Discovery agent	N.A.	Investigative	[8]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Rheumatoid arthritis	FA20	Synovial tissue	4.82E-01	0.11	0.4
Coronary artery disease	BA80-BA8Z	Peripheral blood	5.89E-01	-0.03	-0.14
Osteoarthritis	FA20	Synovial tissue	4.46E-01	0.06	0.18
Type 2 diabetes	5A11	Liver tissue	7.52E-01	1.41E-02	0.09

References

• [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.
• [2] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [3] Clinical pipeline report, company report or official report of xbiotech.
• [4] Target molecules for future hidradenitis suppurativa treatment. Exp Dermatol. 2021 Jun;30 Suppl 1:8-17.
• [5] 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.
• [6] Inhibition of interleukin-1 release by IX 207-887. Agents Actions. 1990 Jun;30(3-4):350-62.
• [7] Cytos Biotechnology AG - Product Pipeline Review - 2013. Global Markets Direct. Dec 2013.
• [8] Identification of regions in interleukin-1 alpha important for activity. J Biol Chem. 1993 Oct 15;268(29):22105-11.