Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTRYK0X)

• DTT Name: Interleukin-1 beta (IL1B)
• Synonyms: IL1F2; IL-1beta; IL-1 beta; Catabolin
• Gene Name: IL1B
• DTT Type: Successful target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL1B_HUMAN
• TTD ID: T42000
• Sequence:
  MAEVPELASEMMAYYSGNEDDLFFEADGPKQMKCSFQDLDLCPLDGGIQLRISDHHYSKG
  FRQAASVVVAMDKLRKMLVPCPQTFQENDLSTFFPFIFEEEPIFFDTWDNEAYVHDAPVR
  SLNCTLRDSQQKSLVMSGPYELKALHLQGQDMEQQVVFSMSFVQGEESNDKIPVALGLKE
  KNLYLSCVLKDDKPTLQLESVDPKNYPKKKMEKRFVFNKIEINNKLEFESAQFPNWYIST
  SQAENMPVFLGGTKGGQDITDFTMQFVSS
• Function: Initially discovered as the major endogenous pyrogen, induces prostaglandin synthesis, neutrophil influx and activation, T-cell activation and cytokine production, B-cell activation and antibody production, and fibroblast proliferation and collagen production. Promotes Th17 differentiation of T-cells. Synergizes with IL12/interleukin-12 to induce IFNG synthesis from T-helper 1 (Th1) cells. Potent proinflammatory cytokine.
• KEGG Pathway:
  MAPK signaling pathway (hsa04010)
  Cytokine-cytokine receptor interaction (hsa04060)
  NF-kappa B signaling pathway (hsa04064)
  Apoptosis (hsa04210)
  Osteoclast differentiation (hsa04380)
  Toll-like receptor signaling pathway (hsa04620)
  NOD-like receptor signaling pathway (hsa04621)
  Cytosolic DNA-sensing pathway (hsa04623)
  Hematopoietic cell lineage (hsa04640)
  TNF signaling pathway (hsa04668)
  Inflammatory mediator regulation of TRP channels (hsa04750)
  Non-alcoholic fatty liver disease (NAFLD) (hsa04932)
  Type I diabetes mellitus (hsa04940)
  Alzheimer's disease (hsa05010)
  Prion diseases (hsa05020)
  Salmonella infection (hsa05132)
  Pertussis (hsa05133)
  Legionellosis (hsa05134)
  Leishmaniasis (hsa05140)
  Chagas disease (American trypanosomiasis) (hsa05142)
  African trypanosomiasis (hsa05143)
  Malaria (hsa05144)
  Amoebiasis (hsa05146)
  Tuberculosis (hsa05152)
  Measles (hsa05162)
  Influenza A (hsa05164)
  Herpes simplex infection (hsa05168)
  Inflammatory bowel disease (IBD) (hsa05321)
  Rheumatoid arthritis (hsa05323)
  Graft-versus-host disease (hsa05332)
• Reactome Pathway:
  Interleukin-1 processing (R-HSA-448706)
  CLEC7A/inflammasome pathway (R-HSA-5660668)
  Interleukin-1 signaling (R-HSA-446652)

Molecular Interaction Atlas (MIA) of This DTT

5 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Canakinumab	DM8HLO5	Autosomal dominant familial periodic fever		Approved	[2]
Gallium nitrate	DMF9O6B	Hypercalcaemia	5B91.0	Approved	[1]
Glucosamine	DM4ZLFD	Osteoarthritis	FA00-FA05	Approved	[3]
Rilonacept	DMGLUQS	Arthritis	FA20	Approved	[4]
Diacerein	DMN2Q5I	N. A.	N. A.	Phase 4	[5]

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
XOMA 052	DMOKQV7	Type-2 diabetes	5A11	Phase 3	[6]
ABT-981	DM6PTIX	Osteoarthritis	FA00-FA05	Phase 2	[7]
AC-201	DMB0TNL	Type-2 diabetes	5A11	Phase 2	[8]
LY-2189102	DMU81BH	Cardiovascular disease	BA00-BE2Z	Phase 2	[9]
CYT-013-IL1bQb	DMNICD4	Inflammation	1A00-CA43.1	Phase 1	[10]
TT-301	DM4QV8Y	Alzheimer disease	8A20	Phase 1	[11]

1 Discontinued Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
CDP-484	DMJTB4E	Immune System disease	4A01-4B41	Discontinued in Phase 1/2	[12]

1 Preclinical Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Celastrol	DMWQIJX	Motor neurone disease	8B60	Preclinical	[13]

1 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
DVD-Ig	DMWF9GQ	Solid tumour/cancer	2A00-2F9Z	Investigative	[10]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Alzheimer's disease	8A00.0	Entorhinal cortex	4.74E-01	8.78E-03	0.02
Type 2 diabetes	5A11	Liver tissue	3.05E-01	0.06	0.26
Lateral sclerosis	8A00.0	Cervical spinal cord	3.94E-01	0.07	0.26
Osteoarthritis	FA20	Synovial tissue	9.07E-01	9.60E-03	0.03
Rheumatoid arthritis	FA20	Synovial tissue	7.50E-01	-0.07	-0.23

References

• [1] Elimination of arthritis pain and inflammation for over 2 years with a single 90 min, topical 14% gallium nitrate treatment: case reports and revie... Med Hypotheses. 2005;65(6):1136-41.
• [2] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [3] Glucosamine inhibits IL-1beta-mediated IL-8 production in prostate cancer cells by MAPK attenuation. J Cell Biochem. 2009 Oct 1;108(2):489-98.
• [4] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [5] Non-surgical treatment of osteoarthritis of large joints - new aspects. Wien Med Wochenschr. 2009;159(3-4):76-86.
• [6] Gevokizumab, an anti-IL-1beta mAb for the potential treatment of type 1 and 2 diabetes, rheumatoid arthritis and cardiovascular disease. Curr Opin Mol Ther. 2010 Dec;12(6):755-69.
• [7] 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.
• [8] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [9] Double-blind, randomized study evaluating the glycemic and anti-inflammatory effects of subcutaneous LY2189102, a neutralizing IL-1beta antibody, in patients with type 2 diabetes. Diabetes Care. 2013Aug;36(8):2239-46.
• [10] 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. (Target id: 2623).
• [11] A Swell in the Armamentarium of Antiepileptic Drug Targets. Epilepsy Curr. 2011 Nov-Dec; 11(6): 172-176.
• [12] Biological targets for therapeutic interventions in COPD: clinical potential. Int J Chron Obstruct Pulmon Dis. 2006 September; 1(3): 321-334.
• [13] Emerging disease-modifying therapies for the treatment of motor neuron disease/amyotropic lateral sclerosis. Expert Opin Emerg Drugs. 2007 May;12(2):229-52.