In:
Chemistry – An Asian Journal, Wiley, Vol. 16, No. 22 ( 2021-11-15), p. 3702-3712
Abstract:
Interleukin‐33 (IL‐33) is an epithelial‐derived cytokine that plays an important role in immune‐mediated diseases such as asthma, atopic dermatitis, and rheumatoid arthritis. Although IL‐33 is considered a potential target for the treatment of allergy‐related diseases, no small molecule that inhibits IL‐33 has been reported. Based on the structure‐activity relationship and in vitro 2D NMR studies employing 15 N‐labeled IL‐33, we identified that the oxazolo[4,5‐ c ]‐quinolinone analog 7 c binds to the interface region of IL‐33 and IL‐33 receptor (ST2), an orphan receptor of the IL‐1 receptor family. Compound 7 c effectively inhibited the production of IL‐6 in human mast cells in a dose‐dependent manner. Compound 7 c is the first low molecular weight IL‐33 inhibitor and may be used as a prototype molecule for structural optimization and investigation of the IL‐33/ST2 signaling pathway.
Type of Medium:
Online Resource
ISSN:
1861-4728
,
1861-471X
DOI:
10.1002/asia.202100896
Language:
English
Publisher:
Wiley
Publication Date:
2021
detail.hit.zdb_id:
2233006-9