Miransertib (ARQ-092) is an orally bioavailable, selective, and potent allosteric Akt inhibitor.

Akt3:8.1 nM, Akt2:14 nM, Akt1:2.7 nM

Miransertib blocks membrane translocation of inactive AKT and even dephosphorylates the membrane-associated active form, thereby perturbing AKT activity. Treatment with 50-500 nM Miransertib significantly blocks αMβ2 integrin function in neutrophils and reduces P-selectin exposure and glycoprotein Ib/IX/V-mediated agglutination in platelets[2]. In a large panel of diverse cancer cell lines, Miransertib inhibits proliferation across multiple tumor types but are most potent in leukemia, breast, endometrial, and colorectal cancer cell lines. Moreover, inhibition by Miransertib is more prevalent in cancer cell lines containing PIK3CA/PIK3R1 mutations compared to those with wt-PIK3CA/PIK3R1 or PTEN mutations[1]. Miransertib targets the PI3K/AKT pathway and AKT specifically and reduces phosphorylation of GSK3α and GSK3β in mutation-positive cells[3].

Cells (MDA-MB-453: 1.5×106; NCI-H1650: 1×106; KU-19-19: 0.7×106) are plated into 6 well plates, left overnight, and then treated with full media containing different concentrations (0, 0.012, 0.037, 0.11, 0.33, and 1 μM) of AKT inhibitors (ARQ 092, ARQ 751, MK-2206, GDC-0068) for 2 hours. Cells are treated under designated conditions and lysates are extracted. Proteins are resolved from extracts using SDS-PAGE followed by immunoblotting. (Only for Reference)