Three related forms of the kinase Akt (1, 2, 3, also known as protein kinase B isoforms PKBα, β, γ) modulate cell proliferation, metabolism, and survival as well as angiogenesis. MK-2206 is an orally active, allosteric Akt inhibitor that is equally potent toward purified human recombinant Akt1 and Akt2 (IC50s = 5 and 12 nM, respectively) and approximately 5-fold less potent against human Akt3 (IC50 = 65 nM). In combination with other anticancer agents including topoisomerase inhibitors, antimetabolites, antimicrotubule agents, DNA cross-linkers or growth factor inhibitors, MK-2206 has been shown to synergistically inhibit cell proliferation of human cancer cell lines. At 5 μM, MK-2206 significantly enhances apoptosis in hematopoietic cells treated with chemotherapeutics.
