Questions remain about the optimal selectivity profiles for PI3K inhibitors, but big biopharmas are already making their bets. The shift from interesting science to investable compounds - about two decades in the making - hinged on marrying discoveries in PI3K biology to the ability of medicinal chemists to tweak the relative selectivity compounds for kinase isoforms that are implicated in a host of cancers, inflammatory diseases and respiratory disorders.

Few of the inhibitors of phosphoinositide 3-kinase (PI3K) now in the clinic, whose selectivity profiles have been disclosed, are uniquely selective for the disease-related isoform of interest. Indeed, even next-generation compounds generally show some activity against all isoforms, and in some cases even show equal activity against two or three isoforms.