Description
MK-2206 (CAS 1032350-13-2) is a potent and selective allosteric inhibitor of Akt (IC50’s: Akt1 = 5 nM, Akt2 = 12 nM, Akt3 = 65 nM) that enhances the?in vitro?and?in vivo?antitumor efficacy of several standard chemotherapeutic agents.1?It was able to decrease insulin-stimulated glucose uptake, glycogen synthesis and glycogen synthase activity in rat muscle.2?MK-2206 induced G1-phase cycle arrest and sensitized HepG2 hepatocellular carcinoma cells to TRAIL-induced apoptosis.3
Uses
AZD 6244 and MK 2206 are targeted small-molecule drugs that inhibit MEK and AKT responses. The combination of AZD6244 and MK2206 has a significant synergistic effect on tumor growth in vitro and in vivo and leads to increased survival rates in mice bearing highly aggressive human lung tumors. Antitumor agents. Potent AKT inhibitor.
Uses
A highly selective inhibitor of Akt. Akt1, IC50=8 nM; Akt2, IC50=12 nM; Akt3, IC50=65 nM.
in vivo
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. No other obvious toxicity is observed in mice[2].
MK-2206 dihydrochloride (orally; 120 mg/kg; alternate days; for 3 weeks) significantly inhibits tumor growth in 3-5 week old athymic nude mice with GEO colon carcinoma cells[3].
| Animal Model: | Four- to 6-week-old male BALB/c nude mice with CNE-2 xenografts[2] |
| Dosage: | 240 mg/kg and 480 mg/kg |
| Administration: | Oral gavage; 240 mg/kg for three times a week; 480 mg/kg for once a week; for 2 weeks |
| Result: | Both doses inhibited the growth of human CNE-2 xenografts in nude mice. |
IC 50
Akt1: 8 nM (IC
50); Akt2: 12 nM (IC
50); Akt3: 65 nM (IC
50)
References
[1] HIROSHI HIRAI. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo.[J]. Molecular Cancer Therapeutics, 2010, 9 7: 1956-1967. DOI:
10.1158/1535-7163.mct-09-1012[2] YU-CHIANG LAI. A novel PKB/Akt inhibitor, MK-2206, effectively inhibits insulin-stimulated glucose metabolism and protein synthesis in isolated rat skeletal muscle.[J]. Biochemical Journal, 2012, 447 1: 137-147. DOI:
10.1042/bj20120772[3] PENG JIAO. MK-2206 induces cell cycle arrest and apoptosis in HepG2 cells and sensitizes TRAIL-mediated cell death.[J]. Molecular and Cellular Biochemistry, 2013, 382 1-2: 217-224. DOI:
10.1007/s11010-013-1737-0
