Discovery of novel and selective IKK-beta serine-threonine protein kinase inhibitors. Part 1.

作者信息

Murata Toshiki, Shimada Mitsuyuki, Sakakibara Sachiko, Yoshino Takashi, Kadono Hiroshi, Masuda Tsutomu, Shimazaki Makoto, Shintani Takuya, Fuchikami Kinji, Sakai Katsuya, Inbe Hisayo, Takeshita Keisuke, Niki Toshiro, Umeda Masaomi, Bacon Kevin B, Ziegelbauer Karl B, Lowinger Timothy B

机构信息

Department of Chemistry, Research Center Kyoto, Bayer Yakuhin, Ltd., Kizu, Soraku, Kyoto 619-0216, Japan.

出版信息

Bioorg Med Chem Lett. 2003 Mar 10;13(5):913-8. doi: 10.1016/s0960-894x(02)01046-6.

IkappaB kinase beta (IKK-beta) is a serine-threonine protein kinase critically involved in the activation of the transcription factor Nuclear Factor kappa B (NF-kappaB) in response to various inflammatory stimuli. We have identified a small molecule inhibitor of IKK-beta. Optimization of the lead compound resulted in improvements in both in vitro and in vivo potency, and provided IKK-beta inhibitors exhibiting potent activity in an acute cytokine release model (LPS-induced TNFalpha).