Miransertib (ARQ-092, MK-7075) is a potent, selective and allosteric pan-Akt inhibitor with IC50 of 2.7 nM, 14 nM and 8.1 nM for Akt1, Akt2, Akt3, respectively.
Miransertib (ARQ-092) also potently inhibits AKT1-E17K mutant inhibitor and phosphorylation of AKT.
Miransertib (ARQ-092) inhibited AKT activation not only by dephosphorylating the membrane-associated active form, but also by preventing the inactive form from localizing into plasma membrane.
Miransertib (ARQ-092) exhibited strong anti-tumor activity in endometrial PDX models harboring mutant AKT1-E17K and other tumor models.
ARQ 092 enhanced tumor inhibition of a common chemotherapeutic agent (paclitaxel).
Miransertib (ARQ-092) inhibited proliferation across multiple tumor types but is most potent in leukemia, breast, endometrial, and colorectal cancer cell lines.
Miransertib (ARQ-092) was more prevalent in cancer cell lines containing PIK3CA/PIK3R1 mutations compared to those with wt-PIK3CA/PIK3R1 or PTEN mutations.