Friday, March 27, 2015

Drugs in Clinical Pipeline: Alpelisib

Alpelisib [(S)-N1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide] is a potent and selective inhibitor of PI3K-alpha (Phosphatidylinositol-3 Kinase-alpha). Alpelisib is currently being investigated in Phase I/II studies in various tumor types, including breast cancer and head and neck cancer.

IUPAC Name: (S)-N1-(4-methyl-5-(2-(1,1,1-trifluoro-2-methylpropan-2-yl)pyridin-4-yl)thiazol-2-yl)pyrrolidine-1,2-dicarboxamide
Common Name: BYL-719; NVP-BYL719
CAS No.: 1217486-61-7; 1584128-91-5 (hydrochloride)
Originator: Novartis

It inhibited P110[alpha], p110[beta], p110[delta], and p110[gamma] with IC50 values of 5 nM, 1.2 µM, 0.29 µM and 0.25 µM, respectively, in biochemical assays.

1. Furet, P.; 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(13), 3741-3748.
2. Fritsch, C.; et. al. Characterization of the novel and specific PI3Ka inhibitor NVP-BYL719 and development of the patient stratification strategy for clinical trials. Mol Cancer Ther 2014, 13(5), 1117-1129.