GSK2110183 - Akt 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK2110183Cat. No.: HY-15966CAS No.: 1047634-63-8分式: CHClFNOS分量: 445.31作靶点: Akt作通路: PI3K/Akt/mTOR储存式: Please store the product under the recommended conditions inthe COA.BIOLOGICAL ACTIVITY物活性 GSK2110183个服有效的，ATP 竞争性的选择性 pan-Akt

2、 抑制剂，作于 Akt1/Akt2/Akt3，Ki 值分别为 0.08/2/2.6 nM。IC50 & Target Akt1 Akt2 Akt3 Akt1 E17K mutant0.08 nM (Ki) 2 nM (Ki) 2.6 nM (Ki) 0.2 nM (IC50)PKG1 PKA PKG1 ROCK0.9 nM (IC50) 1.3 nM (IC50) 4 nM (IC50) 100 nM (IC50)PKC P70S6K RSK1 PKC1210 nM (IC50) 251 nM (IC50) 316 nM (IC50) 430 nM (IC50)PKC510 nM (IC50)

3、体外研究 GSK2110183 is an ATP competitive, time dependant and fully reversible inhibitors of the Akt kinase family.GSK2110183 has a Ki of 0.08, 2 and 2.6 nM against Akt1, Akt2 and Akt3, respectively. GSK2110183 inhibitsthe kinase activity of the E17K Akt 1 mutant protein in a standard kinase assay with

4、EC50 of 0.2 nM 1.体内研究Mice bearing BT474 breast tumor xenografts are dosed orally with either vehicle or GSK2110183 at 10, 30 or100 mg/kg daily for 21 days which result in 8, 37 and 61% TGI, respectively. Mice tolerated GSK2110183well, with 1-3% body weight loss reported after 5 days of dosing which

5、recover over the course of the study.Other tumor xenograft models which possess an activation of the Akt pathway are explored to further1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEdemonstrate compound efficacy. Mice treated with GSK2110183 at 10, 30 and 100 mg/kg result in 23, 37and 97% TGI, re

6、spectively, of SKOV3 xenografts 1.PROTOCOLKinase Assay 1 The potency of compounds against Akt enzymes is measured. Since GSK2110183 and GSK2141795 arehighly potent inhibitors of the 3 isoforms of Akt, the true potency (Ki) of the inhibitors is initially determined atlow enzyme concentrations (0.1 nM

7、 Akt1, 0.7 nM Akt2, and 0.2 nM Akt3) using a filter binding assay and thenconfirmed with progress curve analysis. In the filter binding assay, a pre-mix of enzyme plus inhibitor isincubated for 1 h and then added to a GSK peptide (Ac-KKGGRARTSSFAEPG-amide) and 33P ATP.Reactions are terminated after

8、2 h and the radio labeled Akt peptide product is captured in a phospho-cellulose filter plate. Progress curve analysis utilized continuous real-time fluorescence detection of productformation using the Sox-Akt-tide substrate (Ac-ARKRERAYSF-d-Pro-Sox-Gly-NH2) 1.MCE has not independently confirmed the

9、 accuracy of these methods. They are for reference only.Cell Assay 1 Cell lines are typically grown in RPMI 160 medium containing 10% FBS. Some cell lines are grown in mediaspecified by the vendor. A 3-day proliferation assay using CellTiter-Glo is performed to measure the growthinhibition by the co

10、mpounds at 0-30 M. Cell growth is determined relative to untreated (DMSO) controls.EC50s are calculated from inhibition curves using a 4- or 6-parameter fitting algorithm in the Assay Clientapplication 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.A

11、nimal Mice 1Administration 1 Tumors are initiated by injecting either cells (SKOV3, CAPAN-2 and HPAC) or a tumor fragments (BT474)subcutaneously into 6-8 week female athymic nude (SKOV3) and SCID (all others) mice. Once tumors reachbetween 120 and 300 mm3, mice are randomized according to tumor volu

12、me into groups of n = 7-10 miceper treatment. GSK2110183 (10, 30 or 100 mg/kg daily for 21 days) and GSK2141795 are administered dailyat various doses by oral gavage. In combination experiments, GSK1120212 is also administered daily by oralgavage. Tumor volumes and body weight are measured twice wee

13、kly, tumor volume is measured withcalipers and calculated.MCE has not independently confirmed the accuracy of these methods. They are for reference only.户使本产品发表的科研献 Theranostics. 2019 Jan 30;9(4):1096-1114. Methods Mol Biol. 2018;1711:351-398.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Dumble M, et al. Discovery of novel AKT inhibitors with enhanced anti-tumor effects in combination with the MEK inhibitor. PLoS One.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE2014 Jun 30;9(6):e100