AKT-IN-1 (AZD-26) is an allosteric AKT inhibitor (IC50: 1.04 μM).

Akt (allosteric):1.04 μM

AZD-26 is able to potently inhibit phosphorylation of AKT in cells at both Thr308 (IC50: 0.422 μM) and Ser473 (IC50: 0.322 μM). AZD-26 inhibits the phosphorylation of ribosomal protein S6, a downstream effector of the PI3K-AKT pathway. AZD-26 potently inhibits the phosphorylation of PRAS40 [1].

The effects of AZD-26 in vivo are characterized by measuring the pharmacodynamic activity of AZD-26 in a BT474c breast adenocarcinoma xenograft model. Following acute doses of 100 and 200 mg/kg, AZD-26 potently inhibits the phosphorylation of its downstream substrate GSK3β as well as the phosphorylation of AKT (Ser473), with a potency consistent with its pharmacokinetic profile. The in vivo activity of AZD-26 is further characterized by measuring the effects on the growth of tumour cell xenografts. Continuous (daily) oral dosing of AZD-26 (100 and 200 mg/kg) to nude mice bearing BT474c breast adenocarcinoma xenografts results in inhibition of tumour growth in a dose-dependent manner. When dosed at 200 mg/kg daily, AZD-26 causes significant tumour growth inhibition[1].