GDC-0032

1282512-48-4

GDC-0032 (Taselisib) is a cell permeable, orally bioavailable, and next-generation β isoform-sparing pan PI3K inhibitor. Embedded with unique features, GDC-0032 is a much more upgraded version of GDC-0941 (Pictilisib) in most pharmacological parameters. It potently and selectively inhibits PI3Kα /δ /γ isoforms with IC50 values of 0.29 nM/0.12 nM/0.97nM, with reduced inhibitory potency against PI3Kβ (IC50 >8 nM, >30 fold less potent relative to the PI3Kα isoform). This selectivity and isoform-biased profile has allowed for greater efficacy in vivo at the maximum tolerated dose relative to a pan inhibitor in representative PI3Kα (PIK3CA) mutant xenografts, and noticeably it preferentially inhibited PIK3CA mutant cells relative to cells with wild-type PI3K. It is currently in clinical evaluation.

Store at 0° C (short term), -20° C (long term), desiccated

HPLC-MS, ¹HNMR, and Quantitative Elemental Analysis

1. C. O. Ndubaku, et al, Discovery of 2-{3-[2-(1-isopropyl-3-methyl-1H-1, 2-4-triazol-5-yl)-5, 6-dihydrobenzo[f]imidazo[1, 2-d][1, 4]oxazepin-9-yl]-1H-pyrazol-1-yl}-2-methylpropanamide (GDC-0032): a β -sparing phosphoinositide 3-kinase inhibitor with high unbound exposure and robust in vivo antitumor activity. J Med Chem. 2013 Jun 13; 56(11):4597-610.

2. S. Lopez, et al, Taselisib, a selective inhibitor of PIK3CA, is highly effective on PIK3CA-mutated and HER2/neu amplified uterine serous carcinoma in vitro and in vivo. Gynecol Oncol. 2014 Nov; 135(2):312-7