文献类型：期刊文献

英文题名：Rational Design, Synthesis and Evaluation of Oxazolo[4,5-c]-quinolinone Analogs as Novel Interleukin-33 Inhibitors

作者：Kim, Yujin Ma, Chao Park, Seonghu Shin-, Yujin Lee, Taeyun Paek, Jiwon Kim, Kyong Hoon Jang, Geonhee Cho, Haelim Son, Seyoung Son, Sang-Hyun Lee, Ki Yong Lee, Kiho Jung, Yong Woo Jeon, Young Ho Byun, Youngjoo

第一作者：Kim, Yujin

通信作者：Jung, YW[1];Jeon, YH[1];Byun, Y[1]

机构：[1]Korea Univ, Coll Pharm, 2511 Sejong Ro, Sejong 30019, South Korea;[2]Korea Univ, Dept Biotechnol & Bioinformat, Sejong 30019, South Korea;[3]T&J TECH Inc, 212 Gasan Digital 1 Ro, Seoul 08502, South Korea;[4]Azcuris Co Ltd, 2511 Sejong Ro, Sejong 30019, South Korea;[5]Guizhou Inst Technol, Coll Food & Pharmaceut Engn, Guiyang 550003, Guizhou, Peoples R China

第一机构：Korea Univ, Coll Pharm, 2511 Sejong Ro, Sejong 30019, South Korea

通信机构：corresponding author), Korea Univ, Coll Pharm, 2511 Sejong Ro, Sejong 30019, South Korea.

年份：2021

卷号：16

期号：22

起止页码：3702-3712

外文期刊名：CHEMISTRY-AN ASIAN JOURNAL

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000700474800001)】；

基金：This work was supported by the National Research Foundation funded by the Ministry of Science, ICT & Future Planning (MSIP) and by the Ministry of Education of Korea (2014R1A4A1007304 and 2019R1A6A1A03031807)

语种：英文

外文关键词：Interleukin-33; Allergy; Cytokine; Inhibitors; Oxazoloquinoline

摘要：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 N-15-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.