AZD-8835 is a mixed inhibitor of PI3Kα/δ (IC50: 6.2/5.7 nM), also with selectivity against PI3Kβ/γ (IC50: 431/90 nM).

PI3Kα:6.2 nM, PI3Kβ:431 nM, PI3Kδ:5.7 nM, PI3Kα (H1047R):5.8 nM, PI3Kα (E542K):6 nM, PI3Kγ:90 nM

AZD8835 is a potent inhibitor of PI3Kα (wild type, E545K and H1047R mutations) and PI3Kδ with excellent selectivity vs. PI3Kβ, PI3Kγ and an excellent general kinase selectivity. AZD8835 is a potent inhibitor of p-Akt in cells sensitive to PI3Kα inhibition (IC50=0.057 μM in PIK3CA mutant human breast ductal carcinoma BT474 cell line) and in cells sensitive to PI3Kδ inhibition (IC50=0.049 μM in JeKo-1 B cell line), but not to cells sensitive to PI3Kβ inhibition (IC50=3.5 μM in PTEN null breast adenocarcinoma MDA-MB-468 cell line) or PI3Kγ inhibition (IC50=0.53 μM in monocytic RAW264 cell line)[2].

AZD8835 has antitumor efficacy in corresponding breast cancer xenograft models when dosed continuously and displays high metabolic stability and suitable physical properties for oral administration[1][2].

BT474, MCF7, or T47D cells are seeded in 384-well plates at a density of 500 to 2,000 cells per well and incubated overnight. Cells are dosed with compound(s) and cell confluency is measured at 4-hour intervals over several days.(Only for Reference)