Phosphoinositide 3-kinase-γ as a target in rheumatoid arthritis and systemic lupus

Abstract

Rheumatoid arthritis and systemic lupus erythematosus are autoimmune diseases, which may involve phosphoinositide 3-kinase gamma (PI3Kγ). AS605240 is a new and selective PI3Kγ inhibitor. The direct administration of collagen II-specific antibodies produced the features of rheumatoid arthritis in mice, and when AS605240 was administered orally after the collagen antibodies, it reduced the clinical and histological signs of joint inflammation. Collagen can also be used to induce the clinical and histopathological symptoms similar to rheumatoid arthritis in mice and this can be prevented or reduced by treatment with AS605240. MRL-lpr mice develop lupus-like disease and AS605240 prolonged the life of these mice. MRL-lpr mice also develop kidney disease and this can be reversed with AS605240 treatment. These results suggest that PI3Kγ is a therapeutic target in chronic inflammation and that the PI3Kγ inhibitor AS605240 may have potential in the treatment of chronic inflammatory conditions.

Keywords::

• AS605240
• chronic inflammation
• phosphoinositide 3-kinase-γ
• rheumatoid arthritis
• systemic lupus erythematosus