Inhibitors of NF-Kappa B derived from thalidomide

MEDI 302

Bulbul Pandit, pandit.6@osu.edu1, Esperanza Carcache de Blanco2, Zhigen Hu, Hu@dendrite.pharmacy.ohio-state.edu1, and Pui Kai Li, li.27@osu.edu1. (1) Department of Medicinal Chemistry and Pharmacognosy, The Ohio State University, College of Pharmacy, 500 W 12th Avenue, Columbus, OH 43210, (2) Department of Pharmacy Practice and Administration and Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, 500 West 12th Avenue, Columbus, OH 43210
Nuclear factor kappa B (NF-κB) is a group of transcription factors that initiates up regulation of growth factors, cytokines, cell adhesion molecules, and antiapoptotic proteins which mediate promotion, angiogenesis, metastasis and chemoresistance of tumor. As part of a collaborative drug design and discovery effort to search for inhibitors of NFκB, we used Thalidomide and its modified analogs for the design of NFκB inhibitors. Thalidomide and twenty analogs were evaluated. Thalidomide and two active analogs 5HPP-33 and compound 20 inhibited the TNF-α induced activation of NFκB by inhibiting translocation of (p50/p65) to the nucleus in an ELISA-based assay. They also demonstrated stabilization of IκB α following TNF-α activation, in Hela and DU-145 cells by immuno-blot method. The stabilization of IκB α was demonstrated to be a result of inhibition of its phosphorylation following TNF-αactivation.

 

Poster Session
7:00 PM-9:00 PM, Wednesday, August 22, 2007 BCEC -- Exhibit Hall - B2, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 20, 2007 BCEC -- Exhibit Hall - B2, Sci-Mix

Division of Medicinal Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007