MK-2206 is an orally bioavailable allosteric quinolinotriazolone inhibitor of the serine/threonine protein kinase Akt. It is selectively potent for Akt1, Akt2, and Akt3 at 5 nM, 12 nM, and 65 nM, respectively. MK-2206 inhibits auto-phosphorylation of Akt1/2 at position T308 and S473.

Combination studies with EGFR inhibitors (e.g. erlotinib and lapatinib) in cancer cell lines have shown synergistic effects in a dose-dependent manner [1], inhibiting both PI3K and Ras/Erk pathways. Recent studies indicate that breast cancer cell lines with PTEN loss and/or PIK3CA mutations were also more sensitive to MK-2206 [3], and that targeting eEF-2 kinase in conjunction with Akt can also enhance its antitumor effect [2].