MK 2206 (dihydrochloride)

MK 2206 is an orally active allosteric Akt inhibitor with IC₅₀ of 5 nM/12 nM/65 nM for Akt1/Akt2/Akt3, respectively. IC50 & Target: IC50: 5 nM/12 nM/65 nM (Akt1/Akt2/Akt3)^[1] In Vitro: The NPC cell lines CNE-1, CNE-2, HONE-1, and SUNE-1 are treated with increasing doses of MK-2206 (0-10 μM) for 72 and 96 hours, results in dose- and time-dependent inhibition of cell viability. At 72 and 96 hours, the IC₅₀ values of MK-2206 in CNE-1, CNE-2, and HONE-1 cell lines are 3-5 μM, and in SUNE-1, they are less than 1 μM^[1]. MK-2206 alone more potently inhibits the cell growth of Ras wild-type (WT) cell lines (A431, HCC827, and NCI-H292; IC₅₀s of 5.5, 4.3, and 5.2 μM, respectively) as compared with Ras-mutant cell lines (NCI-H358, NCI-H23, NCI-H1299, and Calu-6; IC₅₀s of 13.5, 14.1, 27.0, and 28.6 μM, respectively), with the exception of NCI-H460, which has a PIK3CA E545K mutation (IC₅₀, 3.4 μM)^[2]. In Vivo: MK-2206 doses (480 mg/kg once a week and 240 mg/kg three times a week) can inhibit the growth of human CNE-2 xenografts in nude mice. In the two MK-2206 groups, the tumor weights are much lighter than the control group (P<0.01). Temporal body weight reduction is observed after receiving the MK-2206 treatment^[1].