AZD8330

AZD8330 (ARRY-424704) is a potent, uncompetitive MEK1/MEK2 inhibitor, with an IC₅₀ of 7 nM. IC50 & Target: IC50: 7 nM (MEK1/MEK2)^[1] In Vitro: AZD8330 is a selective allosteric MEK1/ MEK2 inhibitor. Exposing human osteosarcoma cell lines MOS, U2OS, and 143B to a concentration of 0.5 μM of Trametinib, AZD8330 or TAK-733 for 6 hours, leads to loss of ERK phosphorylation indicating effective MEK inhibition.The activity of these three inhibitors is tested using concentration ranges in six osteosarcoma cell lines: MOS, U2OS, KPD, ZK58, 143b and Saos-2. All three inhibitors decrease viability of MOS and U2OS and strongly affect 143b. By contrast, viability of KPD, ZK58 and Saos-2 is not affected by any of the three inhibitors^[2]. In Vivo: In tumour xenograft models, AZD8330 demonstrates dose-dependent tumour growth inhibition of approximately 90% at tolerated doses (1.0 mg/kg once daily [OD])^[1].