MK-2206 2HCl is a highly selective inhibitor of Akt1/2/3 with IC50 of 8 nM/12 nM/65 nM, respectively.
Targets
Target
Value
In Vitro
Inhibition of Akt Phosphorylation and Activity MK-2206 binds to the Akt PH domain, inhibiting Akt phosphorylation with an IC50 of 5 nM and showing high selectivity for Akt1 (IC50 = 8 nM), Akt2 (IC50 = 12 nM), and Akt3 (IC50 = 65 nM).[1] In multiple human cancer cell lines, MK-2206 inhibits Akt-dependent phosphorylation of downstream targets such as GSK3β, FoxO3a, and PRAS40, indicating its ability to effectively block the Akt signaling pathway.[2]
Anti-Proliferative and Anti-Tumor Effects Breast Cancer: In PTEN-deficient MDA-MB-468 cells, MK-2206 exhibits strong anti-proliferative activity (IC50 = 0.3 μM), whereas it is less effective in PTEN-expressing MCF-7 cells (IC50 = 0.8 μM).[2] Lung, Colorectal, and Neuroblastoma Cancer: MK-2206 demonstrates dose-dependent inhibition of proliferation in A549 (lung cancer), HCT116 (colorectal cancer), and SK-N-AS (neuroblastoma) cells, with GI50 values ranging from 0.1 to 1.0 μM.[3] Nasopharyngeal Cancer: In C666-1 and HONE-1 nasopharyngeal carcinoma cells, MK-2206 significantly reduces Akt phosphorylation, induces G1-phase cell cycle arrest, and promotes apoptosis.[4]
Apoptosis Induction and Reversal of Drug Resistance MK-2206 induces PARP cleavage and Caspase-3 activation, leading to apoptosis when used alone or in combination with chemotherapy agents.[3] Synergistic Effects: MK-2206 enhances the cytotoxicity of Docetaxel and Cisplatin, overcoming PI3K/Akt-dependent drug resistance.[2] Colorectal Cancer: MK-2206 modulates AIF (Apoptosis-Inducing Factor) and Ezrin (cytoskeletal protein), enhancing apoptosis and anti-tumor activity.[5]
Mechanistic Insights and Signaling Pathway Involvement MK-2206 significantly inhibits Akt phosphorylation at Thr308 and Ser473, disrupting downstream targets such as mTOR, GSK3β, and FoxO3a.[1] In nasopharyngeal carcinoma cells, MK-2206 decreases p-Akt and p-mTOR levels, while also downregulating Cyclin D1 and Bcl-2, leading to apoptosis and G1-phase arrest.[4]
References
Yan L, AACR Annual Meeting 2009: Abstract Number: DDT01-1.
Hirai H, et al. Mol Cancer Therapy, 2010, 9(7), 1956-1967. PMID:20571069
Cheng Y, et al. Cancer Res, 2011, 71(7), 2654-2663. PMID: 21460616
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, 8:1827-37. PMID: 25336925
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, 14:145. PMID: 24581231
Store lyophilized at -20ºC, keep desiccated. In lyophilized form, the chemical is stable for 36 months. In solution, store at -20ºC and use within 3 months to prevent loss of potency. Aliquot to avoid multiple freeze/thaw cycles.
溶解性数据
In vitro (25°C)
DMSO
12 mg/mL (24.98 mM)
Water
Insoluble
Ethanol
Insoluble
In vivo
5% DMSO+40% PEG 300+5%Tween80+ 50%H2O
0.59 mg/mL
* <1 mg/ml means slightly soluble or insoluble. * Please note that Adooq tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
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