1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemECCT128930Cat. No.: HY-13260CAS No.: 885499-61-6分式: CHClN分量: 341.84作靶點: Akt; Autophagy作通路: PI3K/Akt/mTOR; Autophagy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 : 36.67 mg/mL (107.27 mM; Nee

2、d ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.9253 mL 14.6267 mL 29.2535 mL5 mM 0.5851 mL 2.9253 mL 5.8507 mL10 mM 0.2925 mL 1.4627 mL 2.9253 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。體內實驗 請根據您的實驗動物和給藥式選擇適當的溶解案，配制前請先配制澄清的儲備液，再依次添加助溶劑(為保證實驗結果的可靠性，體內實驗的作液，建議您現現配，當天使；澄清的儲備液可以根據儲

3、存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.75 mg/mL (8.04 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% (20% SBE-CD in saline)Solubility: 2.75 mg/mL (8.04 mM); Clear solution3. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.75 mg/mL (8.04

4、 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICAL ACTIVITY物活性 CCT128930種有效的選擇性 Akt2 抑制劑 (IC50 為 6 nM)，作于 PKA 激酶 (IC50 為 168 nM) 選擇性28 倍，作于 p70S6K (IC50 為 120 nM) 選擇性 20 倍。IC50 & Target Akt2 p70S6K PKA Autophagy6 nM (IC50) 120 nM (IC50) 168 nM (IC50)體外研究 CCT128930 exhibi

5、ts marked antiproliferative activity and inhibits the phosphorylation of a range of Aktsubstrates in multiple tumor cell lines in vitro, consistent with Akt inhibition. CCT128930 causes a G1 arrestin PTEN-null U87MG human glioblastoma cells, consistent with Akt pathway blockade. CCT128930 is apotent

6、 ATP-competitive Akt inhibitor, which is initially screened at 10 M against a panel of kinasesrepresentative of the human protein kinome. In view of the potential of ATP-competitive inhibitors to cross-react with the closely related AGC class of kinases, the IC50 of CCT128930 against selected AGC ki

7、nases isdetermined. The GI50 values of CCT128930 for growth inhibition are 6.3 M2.2 (n=3) for U87MG humanglioblastoma cells, 0.35 M0.11 (n=4) for LNCaP human prostate cancer cells, and 1.9 M0.80 (n=5) forPC3 human prostate cancer cells, all of which are PTEN-deficient human tumor cell lines 1.體內研究 T

8、he pharmacokinetics of CCT128930 after a single dose of 25 mg/kg are shown. Following i.v.administration, CCT128930 reaches a peak concentration of 6.4 M in plasma and is eliminated with arelatively short half-life, high volume of distribution and rapid clearance, giving an AUC0- of 4.6 Mh.Following

9、 i.p. administration, the peak plasma drug concentration is 4-fold lower and the plasma clearance issimilar to that observed i.v.The corresponding AUC0- is 1.3 Mh, giving an i.p. bioavailability of 29% 1.PROTOCOLKinase Assay 1 Profiling against 50 different human kinases is carried out using 10 M CC

10、T128930 at an ATP concentrationequivalent to the Km for each enzyme. All other enzyme assays are performed 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Cell Assay 1 All cell lines are grown in their recommended culture medium, supplemented with 10%

11、 fetal bovine serum at37C in 5% CO2 and passaged for less than six months prior to replacement from early passage frozenstocks. CCT128930 and LY294002 are made up as 10mM stocks in DMSO. Cells are regularly screened forMycoplasma using a PCR-based assay. Cells are seeded in 96-well plates and allowe

12、d to attach for 36 hoursto ensure exponential growth prior to treatment. In vitro antiproliferative activity is determined using a 96-hourSRB assay, and GI50 values are derived 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 1Administratio

13、n 1 PTEN-null U87MG human glioblastoma cells (2106) are injected subcutaneously (s.c.) in the right flank of 6-8 weeks old female CrTacNCr-Fox1nu mice. For HER2-positive, PIK3CA-mutant BT474 human breastcancer xenografts, cells (5106) are administered s.c. in medium supplemented with matrigel (1:1)

14、into themammary fat pads of female mice implanted s.c. with estradiol pellets (0.025 mg, 90 day release) 3 days2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEpreviously. Animals are randomized and treatment is started with vehicle or CCT128930 when establishedtumors are 100 mm3 in mean volume. Con

15、trol mice receive vehicle only (10% DMSO, 5% Tween 20, 85%saline) and treated mice received 50 mg/kg CCT128930 intraperitoneally (i.p.) daily for 5 days (U87MGhuman glioblastoma xenografts) or 40 mg/kg CCT128930 i.p. twice daily for 5 days (BT474 human breastcancer xenografts). Tumor size and body w

16、eight are monitored three times a week. Tumor size is evaluatedby measurement of 2 orthogonal diameters with calipers and volume is calculated. At the end of the study,tumors are excised and weighed.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 Oncotarget. 2016 May 17;7(20):29131-42.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Yap TA et al. Preclinical pharmacology, antitumor activity, and development of pharmacodynamic markers for the novel, potent AKTinhibit