Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT4GZA4)

• DTT Name: Interleukin-1 receptor-like 1 (IL1RL1)
• Synonyms: Protein ST2
• Gene Name: IL1RL1
• DTT Type: Clinical trial target; [1]
• UniProt ID: ILRL1_HUMAN
• TTD ID: T63229
• EC Number: EC 3.2.2.6
• Sequence:
  MGFWILAILTILMYSTAAKFSKQSWGLENEALIVRCPRQGKPSYTVDWYYSQTNKSIPTQ
  ERNRVFASGQLLKFLPAAVADSGIYTCIVRSPTFNRTGYANVTIYKKQSDCNVPDYLMYS
  TVSGSEKNSKIYCPTIDLYNWTAPLEWFKNCQALQGSRYRAHKSFLVIDNVMTEDAGDYT
  CKFIHNENGANYSVTATRSFTVKDEQGFSLFPVIGAPAQNEIKEVEIGKNANLTCSACFG
  KGTQFLAAVLWQLNGTKITDFGEPRIQQEEGQNQSFSNGLACLDMVLRIADVKEEDLLLQ
  YDCLALNLHGLRRHTVRLSRKNPIDHHSIYCIIAVCSVFLMLINVLVIILKMFWIEATLL
  WRDIAKPYKTRNDGKLYDAYVVYPRNYKSSTDGASRVEHFVHQILPDVLENKCGYTLCIY
  GRDMLPGEDVVTAVETNIRKSRRHIFILTPQITHNKEFAYEQEVALHCALIQNDAKVILI
  EMEALSELDMLQAEALQDSLQHLMKVQGTIKWREDHIANKRSLNSKFWKHVRYQMPVPSK
  IPRKASSLTPLAAQKQ
• Function: Receptor for interleukin-33 (IL-33) which plays crucial roles in innate and adaptive immunity, contributing to tissue homeostasis and responses to environmental stresses together with coreceptor IL1RAP (PubMed:35238669). Its stimulation recruits MYD88, IRAK1, IRAK4, and TRAF6, followed by phosphorylation of MAPK3/ERK1 and/or MAPK1/ERK2, MAPK14, and MAPK8. Possibly involved in helper T-cell function (PubMed:16286016) (Probable). Upon tissue injury, induces UCP2-dependent mitochondrial rewiring that attenuates the generation of reactive oxygen species and preserves the integrity of Krebs cycle required for persistent production of itaconate and subsequent GATA3-dependent differentiation of inflammation-resolving alternatively activated macrophages (By similarity). {ECO:0000250|UniProtKB:P14719, ECO:0000269|PubMed:16286016, ECO:0000269|PubMed:35238669, ECO:0000305|PubMed:19836339}.; [Isoform B]: Inhibits IL-33 signaling. {ECO:0000250|UniProtKB:P14719}.
• KEGG Pathway: 9173 (hsa)
• Reactome Pathway:
  (R-HSA-1257604)
  (R-HSA-6811558)
  (R-HSA-9014843 [Q01638-2])

Molecular Interaction Atlas (MIA) of This DTT

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Astegolimab	DMKOHC5	Chronic obstructive pulmonary disease	CA22	Phase 3	[2]
GSK3772847	DM7J41B	Asthma	CA23	Phase 2	[1]

References

• [1] Efficacy and safety of GSK3772847 in participants with moderate-to-severe asthma with allergic fungal airway disease: A phase IIa randomized, multicenter, double-blind, sponsor-open, comparative trial. PLoS One. 2023 Feb 3;18(2):e0281205.
• [2] Astegolimab, an anti-ST2, in chronic obstructive pulmonary disease (COPD-ST2OP): a phase 2a, placebo-controlled trial. Lancet Respir Med. 2022 May;10(5):469-477.