This excerpt taken from the ARRY 8-K filed Apr 20, 2009.
About p38 and ARRY-614
p38 is a key regulator of the tumor microenvironment, regulating both cytokine production and signaling, as well as modulating apoptosis and survival pathways. In a number of cancers, including hematological malignancies, cytokines regulate growth and survival and it is thought that p38 inhibitors may have an anti-tumor effect in these indications by inhibiting key cytokine signals. MDS is considered a disease of inappropriate apoptosis where cytokines, such as TNF, induce apoptosis in hematopoietic progenitor cells. Therefore, p38 is a high-value target because of its role in both cytokine production and the apoptotic process. MDS is an excellent disease for p38 inhibitor proof-of-concept studies because there are two distinct biological points at which p38 inhibition may restore hematopoiesis. In multiple myeloma, IL-6 plays a role in survival and proliferation of myeloma clones. Inhibiting IL-6 with a p38 inhibitor may have a direct effect against the myeloma cells making multiple myeloma and certain cytokine-dependent solid tumors potential areas for future clinical study with ARRY-614.
ARRY-614 was well tolerated after multiple days of dosing in healthy subjects and demonstrated a good pharmacokinetic profile supporting advancement into clinical proof-of-concept studies.