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Rigel Compound Inhibits Large B-Cell Lymphoma Cell Lines


Posted on 2006-12-12 07:53:00



Rigel Pharmaceuticals, Inc. today presented preclinical results demonstrating that R406/R788, a syk kinase inhibitor, inhibited the proliferation of multiple diffuse large B-cell lymphoma cell lines. R788 is the oral solid dosage formulation of R406. The verbal presentation took place at the American Society of Hematology (ASH) 48th Annual Meeting and Exposition being held this week in Orlando, Florida. The company also announced the publication of additional preclinical results in the December 25th issue of the Journal of Experimental Medicine, demonstrating that R406 blocks the proliferation of tumorigenic pre-B cells in leukemia cell lines. Rigel has filed an Investigational New Drug Application (IND) for R788 in lymphoma and plans to initiate clinical trials in 2007.

According to Rigel, syk kinase appears to amplify B-cell antigen receptor (BCR) signaling, which may be an important survival mechanism in certain B-cell lymphomas, and implicates syk as a possible rational therapeutic target. R406/R788 is a novel syk kinase inhibitor that blocks the activation of mast cells, B-cells and macrophages by blocking IgG signaling. In this study, researchers at the Dana-Farber Cancer Institute and Brigham and Women's Hospital, in conjunction with researchers at Rigel, showed that R406 inhibited proliferation and was cytotoxic in multiple diffuse large B-cell lymphoma cell lines, confirming that R406/R788 may be useful in the treatment of certain B-cell lymphomas.

Diffuse large B-cell lymphoma, the most common type of non-Hodgkin's lymphoma (NHL), is a cancer of the immune system that is usually aggressive and marked by rapidly growing tumors in the lymph nodes, spleen, liver, bone marrow, or other organs.

"More than 54,000 patients are diagnosed with lymphoid malignancies each year. Patients with diffuse large B-cell lymphomas have an average five-year survival rate of only 50 percent," said Margaret A. Shipp, M.D., director of the Dana Farber/Harvard Cancer Center Lymphoma Program, and senior investigator in the ASH study. "New treatments are needed for these aggressive tumors, which is why we are excited about syk-inhibition as a possible novel target."

n this study, deregulated syk kinase activity allowed growth factor-independent proliferation of B lymphocytes and transformed bone-marrow derived pre-B cells that were then able to induce leukemia in an animal model. Treatment of the syk-transformed pre-B cells with R406 demonstrated that R406 allowed these cells to differentiate normally, indicating that inhibiting syk kinase may be a useful approach for the treatment of leukemia.

"The results of both of these studies confirm that syk is a potential target for the treatment of lymphoma and leukemia, which each represent a complex group of different blood-related cancers," stated Donald G. Payan, M.D., executive vice president and chief scientific officer of Rigel. "We have filed an IND for R788 in lymphoma, and look forward to initiating clinical trials in early 2007."


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