MK 2206 is an orally active allosteric Akt inhibitor with IC₅₀ of 5 nM/12 nM/65 nM for Akt1/Akt2/Akt3, respectively.

IC50: 5 nM/12 nM/65 nM (Akt1/Akt2/Akt3)^[1]

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].

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="">^[1].

• [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]. Hirai H, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Therapy, 2010, 9(7), 1956-1967.

  [3]. Jain A, et al. Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. Oncogene. 2017 Aug 10;36(32):4585-4596.

MK-2206 is dissolved in DMSO and stored, and then diluted with appropriate media before use^[1].

The NPC cell lines CNE-1, CNE-2, HONE-1, and SUNE-1 are seeded into 96-well plates at an appropriate density per well. Twenty-four hours after plating, varying concentrations of MK-2206 (0-10 μM) are added to the wells. Cell proliferation is determined by using the Cell Counting Kit 8 at 72 or 96 hours after dosing. The optical density is measured at 450 nm on an enzyme-linked immunosorbent assay reader. The IC₅₀ value is determined as the concentration resulting in 50% cell growth inhibition after a 72 or 96 hours exposure to the drug compared with untreated control cells. All experiments are performed in triplicate in at least three independent experiments^[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

30% Captisol is used to dose the MK-2206^[1].

Mice^[1]
Four- to six-week-old male BALB/c nude mice are used. CNE-2 cells at 1×10⁷/mL are suspended in serum-free medium, and 0.2 mL medium is injected subcutaneously into the right flank of each nude mouse. When mean tumor volume reaches approximately 50 mm³, the mice are randomized into three groups (n=7/group) with approximately equivalent ranges of tumor volume between groups. The MK-2206 is dosed with 30% Captisol. MK-2206 (240 mg/kg, three times a week), MK-2206 (480 mg/kg, once a week), and 30% Captisol diluents are administered by oral gavage for 2 weeks for each group. Tumor growth is measured with calipers every other day, and the tumor volume is calculated by the following formula: volume (mm³)=length×width²×0.5. Mice are killed when mean tumor volume in the control group is larger than 2,000 mm³. Harvested tumor specimens are weighed and fixed in 10% buffered formalin and embedded in paraffin. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

• [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]. Hirai H, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Therapy, 2010, 9(7), 1956-1967.

  [3]. Jain A, et al. Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. Oncogene. 2017 Aug 10;36(32):4585-4596.

480.39

C₂₅H₂₃Cl₂N₅O

1032350-13-2

Room temperature in continental US; may vary elsewhere

DMSO: 4.8 mg/mL (Need ultrasonic and warming)

MK 2206 is prepared in vehicle (30% captisol)^[3].

* "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">

• [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]. Hirai H, et al. MK-2206, an allosteric Akt inhibitor, enhances antitumor efficacy by standard chemotherapeutic agents or molecular targeted drugs in vitro and in vivo. Mol Cancer Therapy, 2010, 9(7), 1956-1967.

  [3]. Jain A, et al. Abl kinase regulation by BRAF/ERK and cooperation with Akt in melanoma. Oncogene. 2017 Aug 10;36(32):4585-4596.