Akt1/2/3 inhibitor
CAS：1032350-13-2
分子式：C25H21N5O.2HCl
分子量：480.39
纯度：98%
存储：Store at -20°C

Background:

MK-2206 dihydrochloride (MK-2206 (2HCl)) is an orally active allosteric AKT inhibitor with IC50s of 5 nM, 12 nM, and 65 nM for AKT1, AKT2, and AKT3, respectively[1].

MK-2206 dihydrochloride (MK-2206 (2HCl)) (0-10 μM; 72 and 96 hours) inhibits the nasopharyngeal carcinoma (NPC) cell lines CNE-1, CNE-2, HONE-1, and SUNE-1 proliferation in dose- and time-dependent manner[1]. MK-2206 dihydrochloride (0-10 μM; 24 and 48 hours) results in a dose-dependent increase in the percentage of cells in G0/G1 phase and a concomitant reduction of cell numbers in S phase in CNE-2 and HONE-1 cells[1]. MK-2206 dihydrochloride (0-10 μM; 24 hours) attenuates phosphorylation levels of PRAS40 and S6 in a dose-dependent manner. MK-2206 does not effect phosphorylation of GSKα/β and AKT[1]. MK-2206 dihydrochloride (0-10 μM; 24 hours) increases the appearance of LC3-II in CNE-2 cells dose-dependently. Microtubule-associated protein 1 LC3 is an essential autophagy protein[1].

Both MK-2206 dihydrochloride (MK-2206 (2HCl)) doses (oral gavage; 480 mg/kg once a week and 240 mg/kg three times a week; for 2 weeks) can inhibit the growth of human CNE-2 xenografts in nude mice. In the two MK-2206 dihydrochloride groups, the tumor weights are much lighter than the control group. Temporal body weight reduction is observed after receiving the MK-2206 dihydrochloride treatment[1]. No other obvious toxicity is observed in mice[1]. MK-2206 dihydrochloride  (orally; 120 mg/kg; alternate days; for 3 weeks) significantly inhibits tumor growth[2].

参考文献:
[1]. Zhao YY, et al. Effects of an oral allosteric AKT inhibitor (MK-2206) on human nasopharyngeal cancer in vitro and in vivo. Drug Des Devel Ther. 2014 Oct 10;8:1827-37.
[2]. Agarwal E, et al. Akt inhibitor MK-2206 promotes anti-tumor activity and cell death by modulation of AIF and Ezrin in colorectal cancer. BMC Cancer. 2014 Mar 1;14:145.