MK-2206-dihydrochloride - Akt 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMK 2206 dihydrochlorideCat. No.: HY-10358CAS No.: 1032350-13-2分式: CHClNO分量: 480.39作靶点: Akt; Autophagy作通路: PI3K/Akt/mTOR; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 20 mg/mL (4

2、1.63 mM; Need ultrasonic)H2O : 3.81 mg/mL (7.93 mM; Need ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0816 mL 10.4082 mL 20.8164 mL5 mM 0.4163 mL 2.0816 mL 4.1633 mL10 mM 0.2082 mL 1.0408 mL 2.0816 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。体内实验 请根据您的实验动物和给药式选择适当的溶解

3、案，配制前请先配制澄清的储备液，再依次添加助溶剂(为保证实验结果的可靠性，体内实验的作液，建议您现现配，当天使；澄清的储备液可以根据储存条件，适当保存；以下溶剂前的百分 指该溶剂在您配制终溶液中的体积占)：1. 请依序添加每种溶剂： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2 mg/mL (4.16 mM); Clear solution2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2 mg/mL (4.16 mM); Clear solution1/

4、3 Master of Small Molecules 您边的抑制剂师www.MedChemEBIOLOGICAL ACTIVITY物活性 MK 2206 dihydrochloride种服有效的 Akt 变构抑制剂，抑制 Akt1/Akt2/Akt3 的 IC50 分别为 5 nM/12nM/65 nM 1。IC50 & Target Akt1 Akt2 Akt3 Autophagy5 nM (IC50) 12 nM (IC50) 65 nM (IC50)体外研究MK-2206 (0-10 M; 72 and 96 hours) inhibits the nasopharyngeal car

5、cinoma (NPC) cell lines CNE-1, CNE-2,HONE-1, and SUNE-1 proliferation in dose- and time-dependent manner 1.MK-2206 (0-10 M; 24 and 48 hours) results in a dose-dependent increase in the percentage of cells inG0/G1 phase and a concomitant reduction of cell numbers in S phase in CNE-2 and HONE-1 cells

6、1.MK-2206 (0-10 M; 24 hours) attenuates phosphorylation levels of PRAS40 and S6 in a dose-dependentmanner. MK-2206 does not effect phosphorylation of GSK/ and AKT 1.MK-2206 (0-10 M; 24 hours) increases the appearance of LC3-II in CNE-2 cells dose-dependently.Microtubule-associated protein 1 LC3 is a

7、n essential autophagy protein 1.Cell Proliferation Assay 1Cell Line: The NPC cell lines CNE-1, CNE-2, HONE-1, and SUNE-1Concentration: 0.08, 0.16, 0.31, 0.63, 1.25, 2.5, 5, 10 MIncubation Time: 72 and 96 hoursResult: At 72 and 96 hours, the IC50 values in CNE-1, CNE-2, and HONE-1 cell lines were 3-5

8、 M, and in SUNE-1, they were less than 1 M.Cell Cycle Analysis 1Cell Line: CNE-2 and HONE-1 cellsConcentration: 0.625, 1.25, 2.5, 5, 10 MIncubation Time: 24 or 48 hoursResult: Induced cell cycle arrest at G1 in a dose-dependent manner.Western Blot Analysis 1Cell Line: SUNE-1 and CNE-2 cellsConcentra

9、tion: 0.625, 1.25, 2.5, 5, 10 MIncubation Time: 24 hoursResult: Inhibited phosphorylation of AKT downstream targets.Cell Autophagy Assay 12/3 Master of Small Molecules 您边的抑制剂师www.MedChemECell Line: CNE-2 cellsConcentration: 0.625, 1.25, 2.5, 5, 10 MIncubation Time: 24 hoursResult: Induced autophagy.

10、体内研究 Both MK-2206 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 groups, the tumorweights are much lighter than the control group. Temporal body weight reduction is observed aft

11、er receivingthe MK-2206 treatment 1.No other obvious toxicity is observed in mice 1.Animal Model: Four- to 6-week-old male BALB/c nude mice with CNE-2 xenografts 1Dosage: 240 mg/kg and 480 mg/kgAdministration: Oral gavage; 240 mg/kg for three times a week; 480 mg/kg for once a week; for 2 weeksResul

12、t: Both doses inhibited the growth of human CNE-2 xenografts in nude mice.户使本产品发表的科研献 Nature. 2018 Aug;560(7719):499-503. Cell. 2014 Feb 13;156(4):771-85. Cancer Cell. 2019 Apr 15;35(4):677-691 Cancer Cell. 2018 Jun 11;33(6):1061-1077.e6. Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Zhao YY, et al. Effects of an oral allosteric AKT inhibitor (MK-2206) on human nasopharyngeal cancer in vitro and in vivo. Drug DesDevel Ther. 2014 Oct 10;8:1827-37.McePdfHeigh