Celgene Corporation and the Joan and Sanford I. Weill Medical College of Cornell University announced that data from an in vitro study determined that thalidomide and IMiDs (Immunomodulatory Drugs) inhibited COX-2 (Cyclooxygenase-2). Based on these data, Celgene and Weill Cornell have expanded their research partnership to an extensive three-year collaboration to evaluate the molecular mechanism by which thalidomide and IMiDs regulate COX-2 expression.
"The knowledge of how thalidomide and IMiDs modulate COX-2 will help us select the appropriate clinical indications for our current drug candidates in development," said David I. Stirling, Chief Scientific Officer of Celgene Corporation. "In addition, understanding the mechanism of action will allow us to design novel drugs targeted at cancer and inflammation."
COX-2 is an enzyme that is induced by numerous cytokines, growth factors, and tumor promoters, including lipopolysaccharide (LPS). It is known to play an important role in promoting inflammation and angiogenesis while inhibiting immune response and apoptosis. In addition to its role in inflammation, recent studies suggest that COX-2 may be pivotal in the maintenance of tumor viability, growth and metastasis.
In the study, conducted at Weill Cornell by Andrew J. Dannenberg and colleagues, a macrophage cell line was treated with either LPS or LPS and thalidomide. Treatment with LPS caused an increase in the amount of COX-2; however, treatment with thalidomide caused a dose-dependent suppression of this effect. IMiDs also inhibited LPS-mediated induction of COX-2.
"These data provide new insights into the antiangiogenic and anti-inflammatory properties of thalidomide and the IMiDs," said Dr. Dannenberg, Director of Cancer Prevention, New York Presbyterian Hospital - Weill Cornell Campus. "Based on these findings and their implications, over the next three years we will further elucidate the mechanism of action by which thalidomide and the IMiDs inhibit COX-2."
The three-year research collaboration between Celgene and Cornell University will evaluate how thalidomide and IMiDs decrease the stability of COX-2 mRNA and determine if the compounds decrease TNF-alpha mRNA by a similar mechanism. An additional goal of the partnership is to identify the molecular targets that cause the reduction of COX-2 levels.