( rker. In a separate study researche...)Pharmacyclics Identifies Functional Biomarkers for its Novel HDAC,Inhibitor and Demonstrates Preclinical Anti-Tumor Activity with,Bruton's Tyrosine Kinase Inhibitors,Health

In a separate study, researchers tested the effects of Pharmacyclics' BTK inhibitor, PCI-31523, on a variety of B cell receptor (BCR) -expressing lymphoma cell lines. Because many lymphomas require an intact BCR for survival, they should be uniquely sensitive to drugs that target the BCR pathway. Results of the study (Abstract #5398) demonstrated that multiple diffuse large B cell lymphoma lines and follicular lymphoma lines are sensitive to PCI-31523, with growth arrest and apoptosis occurring at concentrations as low as 0.5uM.

In other studies, oral dosing of PCI-31523 (10mg/kg qd) resulted in almost complete inhibition of inflammation in an animal model of arthritis, indicating that this compound may be effective in both autoimmune disease and lymphoma.

About HDAC Inhibition and Cancer

Histone deacetylase (HDAC) inhibitors are a new class of anticancer drugs that modulate transcriptional activity in cells and may thus block angiogenesis and cell cycling, key components of tumor proliferation. HDAC inhibitors also appear to promote apoptosis (cell death) and differentiation. These compounds also may improve the efficacy of existing cancer therapies and, because they target the transcription of specific disease-causing genes, may offer new therapeutic approaches to cancer therapy.

About Bruton's Tyrosine Kinase and Immune Diseases

B-cells are immune cells, which are activated by antigens, pathogens or, in the case of autoimmunity, by host tissues. B-cells produce antibodies, which when self-reactive can trigger autoimmune disease. Activation of B-cells is also thought to play a major role in lymphomas where continuous, or tonic, stimulation results in uncontrolled B-cell proliferation. BTK is a tyrosine kinase inside B-cells that plays an early key role in B-cell activation. Drugs that can inhibit BTK may prevent B-cell activation and therefore may play a role in treatment of lymphomas or autoimmune disease. Other ty
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