1394355-87-3

Upstream product

• 6326-83-6 bis(carboxymethyl)trithiocarbonate 
• 220822-26-4 4-<3-(4-methylpiperazin-1-yl)propoxy>aniline 
• 99557-99-0 4-<3-(4-methylpiperazin-1-yl)propoxy>nitrobenzene 

Downstream Products

• 1394356-06-9 C₃₁H₃₂N₄O₄S₂ 
• 1394356-04-7 C₃₁H₃₂N₄O₄S₂ 
• 1394356-05-8 C₃₁H₃₂N₄O₄S₂ 

Relevant academic research and scientific papers

Identification and characterization of potent, selective and metabolically stable IKKβ inhibitor

We have previously reported the identification of a rhodanine compound (1) with well-balanced inhibitory activity against IKKβ and collagen-induced TNFα activated cells. However, we need more optimized compounds because of its instability over plasma and microsome. As part of a program directed toward the optimization of IKKβ inhibitor, we modified a substituent of parent compound to a series of functional groups. Among substituted compounds, fluorine substituent (12) on the para position of phenyl ring restored the stability toward plasma and microsome while retaining inhibitory potency and selectivity against IKKβ over other kinases. Also, we have demonstrated that compound 12 is an ATP non-competitive inhibitor and safe enough to apply to animal experiment from an acute toxicity test.

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

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.