Rigel, a clinical-stage drug development company, announced that it will present data from preclinical studies of multiple potent and selective inhibitors of Janus Kinase 3 (JAK3) at the 2006 World Transplant Congress taking place from 22-27th at the Hynes Convention Centre in Boston, Massachusetts.
The Rigel JAK3 inhibitor compounds were found, to significantly extend allograft survival in animal heart transplant models. These compounds effectively inhibit JAK3-dependent lymphocyte proliferation and are highly selective in an array of off-target assays. The compounds were discovered and characterized, by Rigel and the heart transplant models, were conducted by researchers at Stanford as part of collaboration with Rigel.
"These promising preclinical results suggest that, these drug candidates may provide a new, additional method of immunosuppression, and may result in a safer and more desirable protocol for preventing transplant rejection and treating other T cell-mediated diseases," stated Donald G. Payan, MD, executive vice president and chief scientific officer of Rigel. "We will file an IND with one of the JAK3 inhibitors and plan to pursue JAK3 inhibition in a variety of autoimmune diseases, in addition to transplant rejection therapy."
Organ recipients receive life-long treatment with immunosuppressive drugs in order to prevent organ rejection. With the currently available pharmaceuticals, fewer than 50 per cent have a functioning replacement organ after 10 years. Current anti-rejection therapy suppresses the immune system with a cocktail of drugs including cyclosporine and steroids, the long-term use of which has been shown to cause kidney damage, hypertension, atherosclerosis, and diabetes.
JAK3 is a cytoplasmic tyrosine kinase with expression limited to T cells, B cells, natural killer (NK) cells, mast cells, and macrophages. JAK3 acts in the signal transduction cascade of numerous growth factors critical for lymphocyte (white blood cell) activation, and plays an important role in lymphocyte differentiation and proliferation.