3α-Aminocholestane - Phosphatase 抑制劑 - 生命科學(xué)試劑 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemE3-AminocholestaneCat. No.: HY-19776CAS No.: 2206-20-4分式: CHN分量: 387.68作靶點(diǎn): Phosphatase作通路: Metabolic Enzyme/Protease儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實(shí)驗 Ethanol : 50 mg/mL (128.97 mM; N

2、eed ultrasonic)DMSO : 1 mg/mL (insoluble or slightly soluble)Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.5794 mL 12.8972 mL 25.7945 mL5 mM 0.5159 mL 2.5794 mL 5.1589 mL10 mM 0.2579 mL 1.2897 mL 2.5794 mL請根據(jù)產(chǎn)品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。BIOLOGICAL ACTIVITY物活性 3-Aminocholestane是含有選

3、擇性 SH2 結(jié)構(gòu)域的肌醇-5-磷酸酶 1 (SHIP1) 的抑制劑，其 IC50 值約為 2.5 M。IC50 & Target IC50: 2.5 M (SHIP1) 1體外研究OPM2 cell viability is effectively reduced by 3-Aminocholestane (3AC) treatment. RPMI8226 and U266 cells1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEshow significantly less sensitivity to 3-Aminocholestane

4、 treatment when compare with OPM2 cells, althoughviability is decreased significantly at concentrations of 12.5 M. Treatment with 3-Aminocholestane for 36h severely reduces the percentage of cells in the S phase, which is accompanied by an increase of cells inthe G2/M phase. In contrast, in the less

5、 proliferative RPMI8226 and U266 cells, cell cycle progression isblocked in the G0/G1 phase upon 3-Aminocholestane treatment, in conjunction with a reduced percentageof cells undergoing the S phase 2.體內(nèi)研究 It is found that 3-Aminocholestane (3AC) results in reduced multiple myeloma (MM) growth in viv

6、o, asdetermined by quantitation of free human Ig light chain in the plasma after OPM2 challenge. In addition,reduced numbers of circulating OPM2 cells, as determined by human HLA-ABC staining, is observed inperipheral blood from 3-Aminocholestane-treated mice compare with vehicle controls. Most impo

7、rtantly, 3-Aminocholestane treatment results in significantly enhanced survival of mice after tumor challenge. In 3-Aminocholestane-treated mice that resist treatment, it is found that MM tumors exhibit an upregulation ofSHIP2, reminiscent of in vitro treatment of OPM2 cells and suggesting that SHIP

8、1 inhibition may select fortumor cells with increased SHIP2 expression 2.PROTOCOLCell Assay 2 Cells are treated in triplicate or more with increasing concentrations of compounds (including 3-Aminocholestane). Cell viability is determined with a Cell Counting Kit according to the manufacturersinstruc

9、tions. The odds density (OD) of compound (including 3-Aminocholestane )-treated cells is divided bythe OD of their vehicle control, and the viability is expressed as a percentage of untreated cells. Results areexpressed as meanstandard error of the mean (SEM) of three individual experiments. For pho

10、sphatidylinositol phosphates (PIP) add-back experiments, MCF-7 cells are treated for 2 h with 10 M SHIP inhibitors(including 3-Aminocholestane ), after which cells are washed and fresh medium is added. Cells aresubsequently cultured in the absence (0 M) or presence (10 or 20 M) of either PtdIns(3,4)

11、P2-diC16 (P-3416) or PtdIns(3,5)P2-diC16 (P-3516) for 36 h, after which cell viability is determined by the Cell CountingKit 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal NOD/SCID/cIL2R (NSG) mice are injected intraperitoneally with 1107 OPM2

12、 cells and 6 h later receive anAdministration 2 initial injection of 3-Aminocholestane (3AC) or vehicle. 3-Aminocholestane is suspended in a 0.3%Klucel/H2O solution at 11.46 mM and administered by intraperitoneal injection of 100 L solution. Vehicle-treated mice receive 100 L injection of 0.3% Kluce

13、l/H2O solution. The mice are then treated with 3-Aminocholestane or vehicle daily for the next 6 d and then twice per week in the remaining 15 wks of thesurvival study 2.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產(chǎn)品發(fā)表的科研獻(xiàn) Oxid Med Cell Longev. 2

14、019 Apr.See more customer validations on HYPERLINK / www.MedChemE2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEREFERENCES1. Chen Z, et al. Signalling thresholds and negative B-cell selection in acute lymphoblastic leukaemia. Nature. 2015 May21;521(7552):357-61.2. Gwenny M Fuhler, et al. Therapeutic Potential of SH2 Domain-Containing Inositol-5-Phosphatase 1 (SHIP1) and SHIP2 Inhibition inCancer. Mol Med. 2012 F