BYL719 is a selective inhibitor of phosphoinositide 3-kinase α (PI3Kα) that is equipotent against both wild type and several mutant isoforms (IC50s = 4.0-4.8 nM). It is less effective against PI3K isoforms β, γ, and δ (IC50s = 1,156, 250, and 290 nM) as well as a range of related kinases. BYL719 is effective in vivo, as it dose-dependently inhibits the growth of PI3Kα-dependent xenograft tumors in mice. Effectiveness against wild type and mutant PI3Kα-dependent tumors may be augmented by combination therapy with inhibitors of other kinases. Combination therapy may be necessary, as loss of downstream pathway components can confer clinical resistance to BYL719.
