1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEGSK2110183 hydrochlorideCat. No.: HY-15966ACAS No.: 2070009-64-0分式: CHClFNOS分量: 481.77作靶點: Akt作通路: PI3K/Akt/mTOR儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數據體外實驗 DMSO : 36 mg/mL (74.72 mM)* means so

2、luble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.0757 mL 10.3784 mL 20.7568 mL5 mM 0.4151 mL 2.0757 mL 4.1514 mL10 mM 0.2076 mL 1.0378 mL 2.0757 mL請根據產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 GSK2110183 hydrochloride個服有效的，ATP 競爭性的選擇性 pan-Akt 抑制

3、劑，作于Akt1/Akt2/Akt3，Ki 值分別為 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)1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEPKG1 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

4、) 316 nM (IC50) 430 nM (IC50)PKC510 nM (IC50)體外研究 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 mu

5、tant protein in a standard kinase assay with EC50 of 0.2 nM 1.體內研究 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 weig

6、ht loss reported after 5 days of dosing which recover over the course of the study.Other tumor xenograft models which possess an activation of the Akt pathway are explored to furtherdemonstrate compound efficacy. Mice treated with GSK2110183 at 10, 30 and 100 mg/kg result in 23, 37and 97% TGI, respe

7、ctively, 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 Ak

8、t1, 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 2 h

9、 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 ac

10、curacy 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 compo

11、unds 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.Anim

12、al 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 volume

13、into groups of n = 7-10 miceper treatment. GSK2110183 (10, 30 or 100 mg/kg daily for 21 days) and GSK2141795 are administered daily2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEat various doses by oral gavage. In combination experiments, GSK1120212 is also administered daily by oralgavage. Tumor

14、volumes and body weight are measured twice weekly, tumor volume is measured withcalipers and calculated.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發表的科研獻 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.2014 J