Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy

Hyeseung Song, Yun Suk Lee, Eun Joo Roh, Jae Hong Seo, Kwang Seok Oh, Byung Ho Lee, Hogyu Han, Kye Jung Shin

Research output: Contribution to journalArticlepeer-review

20 Citations (Scopus)


Regulation of NF-κB activation through the inhibition of IKKβ has been identified as a promising target for the treatment of inflammatory and autoimmune disease such as rheumatoid arthritis. In order to develop novel IKKβ inhibitors, we performed high throughput screening toward around 8000 library compounds, and identified a hit compound containing rhodanine moiety. We modified the structure of hit compound to obtain potent and selective IKKβ inhibitors. Throughout hit-to-lead studies, we have discovered optimized compounds which possess blocking effect toward NF-κB activation and TNFα production in cell as well as inhibition activity against IKKβ. Among them, compound 3q showed the potent inhibitory activity against IKKβ, and excellent selectivity over other kinases such as p38α, p38β, JNK1, JNK2, and JNK3 as well as IKKα.

Original languageEnglish
Pages (from-to)5668-5674
Number of pages7
JournalBioorganic and Medicinal Chemistry Letters
Issue number17
Publication statusPublished - 2012 Sept 1


  • Hit-to-lead
  • IKKβ inhibitor
  • NF-κB
  • Reumatoid athritis
  • TNFα

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry


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