AZD1208-hydrochloride - Pim 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEAZD1208 hydrochlorideCat. No.: HY-15604ACAS No.: 1621866-96-3分式: CHClNOS分量: 415.94作靶點(diǎn): Pim作通路: JAK/STAT Signaling儲(chǔ)存式: Please store the product under the recommended conditions inthe COA.溶解性數(shù)據(jù)體外實(shí)驗(yàn) DMSO : 83.3 mg/mL (200.27 mM; Ne

2、ed ultrasonic and warming)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲(chǔ)備液1 mM 2.4042 mL 12.0210 mL 24.0419 mL5 mM 0.4808 mL 2.4042 mL 4.8084 mL10 mM 0.2404 mL 1.2021 mL 2.4042 mL請(qǐng)根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲(chǔ)備液，并請(qǐng)注意儲(chǔ)備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 AZD1208 hydrochloride種新穎的，可服的，具有度選擇性的 PIM 抑制劑。IC50 & Tar

3、get PIM 1體外研究AZD1208 hydrochloride shows good antiproliferative activity in a megakaryoblastic leukemia cell line, MOLM-16, with GI50 values less than 100 nM 1. AZD1208 hydrochloride (10 M) inhibits the growth of Ramoscells, and at 1 M, strongly inhibits PIM kinases in all cells at 1 M. AZD1208 hydr

4、ochloride inducesapoptosis, and PIM2 knockdown is mainly associated with an alteration of the cell cycle 2. The combinationof AZD1208 hydrochloride and AZD2014 rapidly activates AMPK, a negative regulator of translation1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmachinery through mTORC1/2 signa

5、ling in AML cells; profoundly inhibits AKT and 4EBP1 activation; andsuppresses polysome formation 3.PROTOCOLKinase Assay 1 The activity of purified human PIM-1, PIM-2 and PIM-3 enzymes on substrate FL-Ahx-Bad is determinedusing a mobility shift assay on a reader. The PIM-1 assay is performed in a 12

6、 mL reaction containing 50 mMHEPES (pH 7.5), 1 mM DTT, 0.01% Tween 20, 50 mg/mL BSA, 10 mM MgCl2, 1.5 mM FL-Ahx-Bad peptide,100 mM ATP, 2.5 nM PIM-1 and various amount of inhibitor. The reaction is quenched after 90 minuteincubation at 25C with 5 mL of stop mix consisting of 100 mM HEPES, 121 mM EDT

7、A, 0.8% CoatingReagent 3 and 0.01% Tween 20. The ATP and enzyme concentrations for the PIM-2 assay are 5 mM and2.5 nM, respectively, while 50 mM of ATP and 0.33 nM of enzyme is used for PIM-3 assays. For high ATPscreenings, 5 mM ATP is used with 0.67 nM enzyme for both PIM-1 and PIM-2 or 0.11 nM PIM

8、-3.Fluorescence of phosphorylated and unphosphorylated substrate is detected and a ratiometric value iscalculated to determine percent turnover. IC50 values are determined from dose-response data usingsoftware 1.MCE has not independently confirmed the accuracy of these methods. They are for referenc

9、e only.Cell Assay 1 MOLM-16 cells, purchased from DSMZ and cultured in RPMI containing 10% fetal bovine serum (FBS) and1% L-glutamine, are plated at 20,000 cells per well in 96 well plates overnight. Cells are treated for 72 hourswith compound (including AZD1208 hydrochloride) or control vehicle (di

10、methyl sulfoxide) and cell viability ismeasured after the addition of Cell Titer-Blue for 4 hours at 37C and reading of fluorescence on a TecanInfinite 200. The GI50 is determined by calculating growth at each dose relative to vehicle treated cells andcell viability at the time of treatment 1.MCE ha

11、s not independently confirmed the accuracy of these methods. They are for reference only.戶(hù)使本產(chǎn)品發(fā)表的科研獻(xiàn) Science. 2017 Dec 1;358(6367). Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. Nat Commun. 2019 Apr 23;10(1):1844. Eneuro. 2019 Aug. Charles University Faculty of Science. 2019 JunSee more custom

12、er validations on HYPERLINK / www.MedChemEREFERENCES1. Dakin LA, et al. Discovery of novel benzylidene-1,3-thiazolidine-2,4-diones as potent and selective inhibitors of the PIM-1, PIM-2, andPIM-3 protein kinases. Bioorg Med Chem Lett. 2012 Jul 15;22(14):4599-604.2. Kreuz S, et al. Loss of PIM2 enhan

13、ces the anti-proliferative effect of the pan-PIM kinase inhibitor AZD1208 in non-Hodgkin lymphomas.Mol Cancer. 2015 Dec 8;14:205.2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemE3. Harada M, et al. The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acutemyeloid leukemia via HSF pathway suppression. Oncotarget. 2015 Nov 10;6(35):37930-47.Mc