BET bromodomain inhibition suppresses Th17-mediated pathology

http://constpharma.wpengine.com/wp-content/uploads/2013/10/J-Exp-Med-2013-Mele-jem-201303761.pdfConstellation Pharmaceuticals Announces New Preclinical Data on Novel BET Bromodomain Inhibitors Published in the Journal of Experimental Medicine

Results Demonstrate Therapeutic Benefit of BET Inhibition in Autoimmune Disease Models

CAMBRIDGE, Mass. – October 8, 2013Constellation Pharmaceuticals, Inc., a clinical-stage biopharmaceutical company in the field of epigenetics, today announced the publication of a study in the The Journal of Experimental Medicine demonstrating that small molecule inhibitors selectively targeting BET bromodomains can suppress T helper 17 (TH17) differentiation and TH17-mediated pathology in models of autoimmune diseases. The paper appears in the online early edition of J Exp Med published the week of October 7, 2013.

During the last decade, researchers have uncovered the importance of TH17 cells as an integral part of the immune system that protects the human body from infections. However, this research has also shown that, when pathologically activated, these cells can attack multiple organs in the body and trigger autoimmune diseases such as multiple sclerosis, rheumatoid arthritis and psoriasis. Because of the important roles that TH17 cells play in both normal and dysregulated immune function, many academic, biotech and pharmaceutical laboratories have research programs devoted to targeting TH17 cells.

“In our study, we show that BET bromodomains are important in the process that differentiates naïve T cells into TH17 cells, by controlling the expression of several key cytokines, such as IL-21 and IL-17. These effects result in remarkable efficacy in experimental models of multiple sclerosis and rheumatoid arthritis. The picture that emerges, together with work from other groups, is that BET bromodomains control the immune response in very profound ways,” said Jose Lora, Ph.D., executive director of preclinical sciences at Constellation and lead author of the study.

“The work which implicates BET bromodomains as key controllers of T cell differentiation into TH17 cells is of fundamental interest in the field, but also has potential importance for patients suffering from TH17 cell-driven diseases.  Our commitment at Constellation is to translate these promising discoveries into novel therapeutic approaches for patients,” commented Jim Audia, Ph.D., chief scientific officer at Constellation.

 

View full paper here

 

About Constellation Pharmaceuticals
Constellation Pharmaceuticals leverages insights from the rapidly expanding field of epigenetics to discover and develop small molecule therapeutics for the treatment of cancer, inflammatory/immunologic disorders and other diseases. Research at Constellation and by others has shown that abnormal epigenetic regulation of gene expression contributes to many different
diseases. The company’s innovative product discovery engine targets both the enzymes that modify the dynamic structure of chromatin and other proteins that interact with chromatin to control gene expression. Restoration of normal gene expression through chromatin modulation by highly selective and specific inhibitors promises to be a powerful avenue for the development of important new medicines against a broad range of diseases. Constellation’s efforts in epigenetics are supported in part through a research collaboration with Genentech. For more information, please visit the company's website at constpharma.wpengine.com.

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