PI3Kγ inhibition:: towards an 'aspirin of the 21st century'?

Class IB phosphatidylinositol 3-kinase p110 gamma (PI3K gamma) has gained increasing attention as a promising drug target for the treatment of inflammatory disease. Extensive target-validation data are available, which are derived from studies using both pharmacological and genetic tools. More recent findings have uncovered further therapeutic applications for PI3K gamma inhibitors, opening up potentially huge opportunities for these drugs. Several companies have been pursuing small-molecule PI3K gamma inhibitor projects, but none of them has progressed to the clinic yet. Here, we discuss the insights gained so far and the main challenges that are emerging on the path to developing PI3K gamma inhibitors for the treatment of human disease.