ETP-46321 是PI3Kα和PI3Kδ抑制剂，KIAPp分别为 2.3 和 14.2 nM。

ETP-46321 is an effective and orally bioavailable PI3Kα/PI3Kδ inhibitor (Ki: 2.3/14.2 nM).

ETP-4632 has been profiled and shown to be a potent PI3K α and δ inhibitor, highly selective versus mTOR and 288 representative kinases. ETP-46321 is also tested against three of the p110α mutant enzymes detected in human cancers (E542K, E545K, and H1047R), being equipotent against these mutants when compared to the wild type protein (Kiapp=2.33, 1.77 and 1.89 nM for PI3Kα-H1047R, PI3Kα-E545K and PI3Kα-E542K, respectively). ETP-46321 inhibits the phosphorylation of AKT in the U2OS cell line (IC50: 8.3 nM).

ETP-46321 is selected for in vivo studies based on its appealing pharmacokinetic profile in BALB-C mice, low in vivo Clearance (0.6 L/h/Kg) and good oral bioavailability (90%). ETP-46321 demonstrates a good pharmacokinetic profile in mice and is selected for preliminary in vivo evaluation in a lung tumor mouse model driven by a K-RasG12V oncogenic mutation, showing significant tumor growth inhibition.

BALB/C mice are treated daily with ETP-46321 (50 mg/kg, p.o.) for three weeks. Tumor volumes of four mice in each treatment group are measured and compared to the starting volume at the beginning of the treatment.

1252594-99-2

C20H27N9O3S

473.55

DMSO:30 mg/mL (63.35 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years