Bruton's Tyrosine Kinase (BTK) Inhibitor Program
BTK is an important cell signaling enzyme that is found in hematopoietic (blood) cells including B-cells. B-cell activation is driven by the B-cell receptor (BCR), and BTK is a crucial part of the BCR signaling pathway.
BCR signaling is thought to promote cell proliferation, adhesion, and survival in many types of B-cell malignancies (cancers). Inhibitors of BTK such as the Pharmacyclics compound, ibrutinib (PCI-32765), act downstream of the BCR and block BTK activity, and in preclinical models this resulted in an inhibition of proliferation, a disruption of tumor cell adhesion, and apoptosis (cell death) in malignant B-cells. Inhibition of BTK also blocked the recruitment and function of other immune cells including monocytes, macrophages, and mast cells. Studies in mice have shown that orally-dosed ibrutinib reduces the level of circulating autoantibodies and can reverse the course of arthritis. Ibrutinib also inhibited auto-antibody production and the development of kidney disease in a mouse model of systemic lupus erythematosus (SLE).
Therefore, targeted inhibition of BTK is a novel approach for treating many different human diseases associated with the inappropriate activation of B-cells, including B-cell malignancies, and potentially autoimmune and inflammatory disorders.
Pharmacyclics' BTK Inhibitor, ibrutinib, is an investigational, orally active, selective and irreversible small molecule that is in clinical development in a variety of B-cell malignancies (including chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), and diffuse large B-cell lymphoma (DLBCL) and multiple myeloma (cancer of plasma cells, a type of white blood cell present in bone marrow).