Alpelisib (BYL719)

BYL719 is an inhibitor of phosphoinositide 3-kinase α (PI3Kα; IC₅₀s = 4.6, 4, and 4.8 nM for wild-type, E545K mutant, and H1047R mutant PI3K, respectively). It is selective for PI3Kα over PI3Kβ, PI3Kδ, PI3Kγ, and PI4Kβ (IC₅₀s = 1,156, 290, 250, and 581 nM, respectively), as well as VPS34, mTOR, DNA-PK, and ATR (IC₅₀s = >9,100 nM for all). BYL719 (12.5, 25, and 50 mg/kg) reduces tumor volume in a PI3Kα-dependent Rat1-myr-p110α mouse xenograft model. It also reduces tumor burden in THP-1 acute myeloid leukemia (AML) and MCF-7 breast cancer mouse xenograft models. Formulations containing BYL719 have been used in the treatment of advanced or metastatic breast cancer.

(2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide is a newly developed phosphatidylinositol-3-kinase (PI3K) inhibitor and a mTOR inhibitor for the treatment of proliferative diseases.

(2S)-N1-[4-Methyl-5-[2-(2,2,2-trifluoro-1,1-dimethylethyl)-4-pyridinyl]-2-thiazolyl]-1,2-pyrrolidinedicarboxamide is a newly developed phosphatidylinositol-3-kinase (PI3K) inhibitor and a mTOR inhibit or for the treatment of proliferative diseases.

ChEBI: (2S)-N1-[4-methyl-5-[2-(1,1,1-trifluoro-2-methylpropan-2-yl)-4-pyridinyl]-2-thiazolyl]pyrrolidine-1,2-dicarboxamide is a proline derivative.

PI3Kα

1. furet p, guagnano v, fairhurst ra et al. discovery of nvp-byl719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation. bioorg med chem lett 2013; 23: 3741-3748. 2. azab f, vali s, abraham j et al. pi3kca plays a major role in multiple myeloma and its inhibition with byl719 decreases proliferation, synergizes with other therapies and overcomes stroma-induced resistance. br j haematol 2014; 165: 89-101. 3. juric d, argiles g, burris h et al. phase i study of byl719, an alpha-specific pi3k inhibitor, in patients with pik3ca mutant advanced solid tumors: preliminary efficacy and safety in patients with pik3ca mutant er-positive (er+) metastatic breast cancer (mbc). cancer res 2012; 72: p6-10.