Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy
- Discovery of potent and selective rhodanine type IKKβ inhibitors by hit-to-lead strategy
- 송혜승; 이윤석; 노은주; 서재홍; 오광석; 이병호; Hogyu Han; 신계정
- IKKβ inhibitor; allosteric inhibitor; anti-inflammation; NF-κB; TNFα; Hit-to-lead
- Issue Date
- Bioorganic & medicinal chemistry letters
- VOL 22, NO 17, 5668-5674
- 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.
- Appears in Collections:
- KIST Publication > Article
- Files in This Item:
There are no files associated with this item.
- RIS (EndNote)
- XLS (Excel)
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.