Miransertib(ARQ 092)

ARQ 092 is a novel, orally bioavailable and selective AKT pathway inhibitor exhibiting a manageable safety profile among patients with advanced solid tumors.

ARQ 092 blocks membrane translocation of inactive AKT and even dephosphorylates the membrane-associated active form, thereby perturbing AKT activity. Treatment with 50-500 nM ARQ 092 significantly blocks M2 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, ARQ 092 inhibits proliferation across multiple tumor types but are most potent in leukemia, breast, endometrial, and colorectal cancer cell lines. Moreover, inhibition by ARQ 092 is more prevalent in cancer cell lines containing PIK3CA/PIK3R1 mutations compared to those with wt-PIK3CA/PIK3R1 or PTEN mutations[1]. ARQ 092 targets the PI3K/AKT pathway and AKT specifically and reduces phosphorylation of GSK3 and GSK3 in mutation-positive cells[3].