|Product Name||AZD8186||CAS No.||1627494-13-6|
|Molecular Weight||457.47||Molecular Formula||C24H25F2N3O4|
AZD8186 is an isoform-specific small-molecule PI3K inhibitor, potently inhibits PI3Kβ (IC50=4 nM) and PI3Kδ (IC50=12 nM) with selectivity over PI3Kα (IC50=35 nM) and PI3Kγ (IC50=675 nM). IC50 value: 4 nM (PI3Kβ), 12 nM (PI3Kδ) Target: PI3K in vitro: AZD8186 selectively inhibits PI3Kβ- and δ-mediated signaling through AKT. AZD8186 inhibits PI3Kβ-dependent activation of pAKT (Ser473) with an IC50 value of 3 nM in the PTEN-null line MDA-MB-468. AZD8186 inhibits IgM-stimulated phosphorylation of pAKT (Ser473) activation in JEKO cells with an IC50 value of 17 nM. In cell proliferation assays, AZD8186 inhibits proliferation of MDA-MB-468 cells with a GI50 value of 65 nM, IgM stimulated JEKO cell growth with an IC50 value of 228 nM. It only inhibits BT474c cell growth with an IC50 value of 1.981 μM consistent with its selectivity for PI3Kβ over PI3Kα. in vivo: AZD8186 modulates pathway biomarkers and inhibits growth of breast and prostate tumor models. In mouse, AZD8186 has a short half-life delivering a PK profile that results in intermittent cover over a 24 hours dosing interval. AZD8186 selectively modulates AKT activation in PTEN-null tumor tissues.