Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5MD4P)

• DTT Name: Interleukin-33 (IL33)
• Synonyms: Nuclear factor from high endothelial venules; NFHEV; NF-HEV; Interleukin1 family member 11; Interleukin-1 family member 11; IL1F11; IL-33; IL-1F11; C9orf26
• Gene Name: IL33
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Cytokine: interleukin
• UniProt ID: IL33_HUMAN
• TTD ID: T23797
• Sequence:
  MKPKMKYSTNKISTAKWKNTASKALCFKLGKSQQKAKEVCPMYFMKLRSGLMIKKEACYF
  RRETTKRPSLKTGRKHKRHLVLAACQQQSTVECFAFGISGVQKYTRALHDSSITGISPIT
  EYLASLSTYNDQSITFALEDESYEIYVEDLKKDEKKDKVLLSYYESQHPSNESGDGVDGK
  MLMVTLSPTKDFWLHANNKEHSVELHKCEKPLPDQAFFVLHNMHSNCVSFECKTDPGVFI
  GVKDNHLALIKVDSSENLCTENILFKLSET
• Function: Involved in the maturation of Th2 cells inducing the secretion of T-helper type 2-associated cytokines. Also involved in activation of mast cells, basophils, eosinophils and natural killer cells. Acts as a chemoattractant for Th2 cells, and may function as an "alarmin", that amplifies immune responses during tissue injury. Cytokine that binds to and signals through the IL1RL1/ST2 receptor which in turn activates NF-kappa-B and MAPK signaling pathways in target cells.
• KEGG Pathway:
  Cytosolic DNA-sensing pathway (hsa04623)
  Influenza A (hsa05164)
• Reactome Pathway:
  Ub-specific processing proteases (R-HSA-5689880)
  PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling (R-HSA-6811558)
  Interleukin-33 signaling (R-HSA-9014843)
  PIP3 activates AKT signaling (R-HSA-1257604)

Molecular Interaction Atlas (MIA) of This DTT

6 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Itepekimab	DMR8NDD	Chronic obstructive pulmonary disease	CA22	Phase 3	[2]
MEDI3506	DMDI7SA	Chronic obstructive pulmonary disease	CA22	Phase 3	[3]
SAR440340	DMKYXSS	Chronic obstructive pulmonary disease	CA22	Phase 3	[2]
Tozorakimab	DMCXN80	Acute respiratory failure	CB41.0	Phase 3	[4]
AMG 282	DM92YWD	Asthma	CA23	Phase 1	[1]
PF-07264660	DM0GI2H	Atopic dermatitis	EA80	Phase 1	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Asthma	CA23	Nasal and bronchial airway	1.19E-01	-0.03	-0.03

References

• [1] Clinical pipeline report, company report or official report of Amgen.
• [2] Efficacy and Safety of Itepekimab in Patients with Moderate-to-Severe Asthma. N Engl J Med. 2021 Oct 28;385(18):1656-1668.
• [3] ClinicalTrials.gov (NCT05742802) A Phase III, Multicentre, Randomised, Double-blind, Chronic-dosing, Parallel-group, Placebo-controlled Extension Study to Evaluate the Long-term Efficacy and Safety of Tozorakimab (MEDI3506) in Participants With Chronic Obstructive Pulmonary Disease (COPD) With a History of Exacerbations. U.S.National Institutes of Health.
• [4] ACCORD: A Multicentre, Seamless, Phase 2 Adaptive Randomisation Platform Study to Assess the Efficacy and Safety of Multiple Candidate Agents for the Treatment of COVID-19 in Hospitalised Patients: A structured summary of a study protocol for a randomised controlled trial. Trials. 2020 Jul 31;21(1):691.
• [5] Clinical pipeline report, company report or official report of Pfizer