Novel Small Molecule Inhibitors Targeting the IL-6/STAT3 Pathway or IL-1β

Jihye Yoo, Darong Kim, Jiyoung Park, Young Kook Kim, Hea Young Park Choo, Hyun Ae Woo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Development of small molecules that inhibit inflammatory cytokines is a desirable strategy for the treatment of inflammatory diseases such as rheumatoid arthritis (RA). Following up a previous study, we synthesized 10 novel compounds with a 2,5-diaminobenzoxazole moiety and evaluated their biological activities. Among them, compound 3e showed potent inhibitory activity on Interleukin 6 (IL-6)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling inhibition (71.5%), and 3a showed excellent inhibitory activity on Interleukin 1 (IL-1β) (92.1%). To test in vivo anti-inflammatory activity, compounds 3a and 3e were administered by intraperitoneal (IP) injection after subcutaneous (SC) injection of zymosan A into the right footpad of mice. Inflammation on the footpad was reduced after administration of compounds 3a and 3e. Especially, compound 3a showed a significant ameliorative effect on zymosan-induced inflammation. From the in vivo and in vitro test results, we confirmed that our synthesized compounds are effective on the RA animal model through inhibition of the IL-6/STAT3 signaling pathway. Since drugs developed with small molecule inhibitors have several advantages over biological drugs, further study on these compounds is needed for the development of potent SMI drugs on RA.

Original languageEnglish
Article number2696
Issue number9
StatePublished - 1 May 2022

Bibliographical note

Funding Information:
Funding: This research was funded by grants from the National Research Foundation of Korea (2021R1A2C2095037 and 2021R1C1C2006086) and from the Korea Basic Science Institute (National Research Facilities and Equipment Center) funded by the Ministry of Education (2021R1A6C103A408).

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  • 2,5-diaminnobenzoxazole
  • Anti-inflammatory effect
  • IL-1β
  • IL-6
  • Rheumatoid arthritis
  • Small molecule inhibitors
  • Zymosan A


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