产品说明书

MK-2206 2HCl

Print
Chemical Structure| 1032350-13-2 同义名 : MK-2206 (2HCl);MK-2206 (hydrochloride);MK-2206 dihydrochloride
CAS号 : 1032350-13-2
货号 : A145592
分子式 : C25H23Cl2N5O
纯度 : 99%+
分子量 : 480.389
MDL号 : MFCD14584463
存储条件：

粉末 Inert atmosphere,Store in freezer, under -20°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 12 mg/mL(24.98 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 3 mg/mL(6.24 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：

5% DMSO+40% PEG 300+5%Tween80+ 50%water 0.625 mg/mL

生物活性
靶点

  • Akt3

    Akt3, IC50:65 nM

  • Akt1

    Akt1, IC50:8 nM

  • Akt2

    Akt2, IC50:12 nM
描述 AKT is the central node of PI3K/AKT/ mTOR pathway. Inactivated AKT adopts a conformation such that the PH domain can interact with the kinase domain with both Thr308 and Ser473 residues shielded from PDK1 phosphorylation[1]. MK-2206 is an oral allosteric of Akt1/2/3 with IC50 value of 8nM, 12nM and 65nM, respectively. MK-2206 can inhibit phosphorylation of both Akt T308 and S473, as well as prevent Akt-mediated phosphorylation of down-stream signaling molecules, such as TSC2, PRAS40 and ribosomal S6 proteins[2]. In vitro, MK-2206 can inhibit the growth of NPC cell lines at 72 and 96 hours with IC50 values less than 1μM, as well as induce cell cycle arrest at the G1 phase, but without apoptosis. Treatment with MK-2206 on the dose of 480mg/kg once a week or 240mg/kg three times a week can inhibit the growth of human CNE-2 xenografts in nude mice[3]. A phase 1 study shows that maximal inhibition of Akt occurred about 6h after an oral dose of MK-2206 and led to Akt inhibition (measured in whole blood) for up to 24h. Clinical studies of MK2206 for the treatment of different kinds of cancer have been done, such as phase 2 study for recurrent platinum-resistant ovarian, fallopian tube, peritoneal cancer and adenoid cyst carcinoma (see in https://clinicaltrials.gov/). Synergy of MK-2206 combined with other targeted therapies has been proposed[4].
作用机制 MK-2206 is an allosteric inhibitor of the AKT which binds to both the PH domain and the kinase domain, then forms a stabilized “closed” complex not capable of having any kinase activity or being activated by PDK1.
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
22RV1 Growth Inhibition Assay IC50=21.5685 μM SANGER
5637 Growth Inhibition Assay IC50=9.84984 μM SANGER
639-V Growth Inhibition Assay IC50=18.3354 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.08mL

0.42mL

0.21mL

10.41mL

2.08mL

1.04mL

20.82mL

4.16mL

2.08mL
参考文献

[1]Keane NA, Glavey SV, et al. AKT as a therapeutic target in multiple myeloma. Expert Opin Ther Targets. 2014 Aug;18(8):897-915.

[2]MK-2206: A potent oral allosteric AKT inhibitor

[3]Hirai H, Sootome 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 Ther. 2010 Jul;9(7):1956-67.

[4]Pal SK, Reckamp K, et al. Akt inhibitors in clinical development for the treatment of cancer. Expert Opin Investig Drugs. 2010 Nov;19(11):1355-66.

[5]Meuillet EJ, et al. Novel inhibitors of AKT: assessment of a different approach targeting the pleckstrin homology domain. Curr Med Chem. 2011;18(18):2727-42.