MKC9989 - IRE1 抑制剂 - 生命科学试剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEMKC9989Cat. No.: HY-12399CAS No.: 1338934-20-5分式: CHO分量: 336.34作靶点: IRE1作通路: Cell Cycle/DNA Damage储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 50 mg/mL (148.66 mM)H2O : 40% PEG300 5% Twe

2、en-80 45% salineSolubility: 2.5 mg/mL (7.43 mM); Clear solutionBIOLOGICAL ACTIVITY1/2 Master of Small Molecules 您边的抑制剂师www.MedChemE物活性 MKC9989种 HAA 抑制剂，且能抑制 IRE1 其 IC50 值在 0.23 M 44 M 的范围之间。IC50 & Target IC50: 0.23 to 44 M (IRE1) 1体外研究 At 10 M concentration, MKC9989 completely inhibits both basal an

3、d thapsigargin induced splicing of XBP1mRNA. These effects are observed even in cells pre-treated with thapsigargin, indicating that MKC9989 canfully reverse the onset of XPB1 splicing after the UPR is initiated. In parallel analysis, MKC9989, significantlystabilizes the RIDD target CD59 mRNA when c

4、o-administered with thapsigargin relative to thapsigargintreatment alone and modestly increases levels of CD59 mRNA in non-stressed cells, the latter likely reflectsthe inhibition of baseline RIDD activity. In contrast to effects on XBP1 splicing, MKC9989 moderatelystabilizes CD59 levels when admini

5、stered 2 hour post treatment with thapsigargin. Finally, the potency ofMKC9989 against the splicing of XBP1 mRNA (EC50=0.33 M) is comparable to its potency against RNAcleavage in vitro 1.PROTOCOLCell Assay 1 Human RPMI 8226 plasmacytoma cells are grown in monolayer culture using medium (DMEM)supplem

6、ented with 10% fetal calf serum (FCS) at 37C and 5% CO2. MKC9989 is prepared as 10 mM stocksin DMSO, stored at -20C, and diluted in medium. Thapsigargin (Tg) is resuspended in DMSO and diluted inmedium. Cells are grown to 50% confluency, treated with 1 M Tg and/or 10 M MKC9989 at the indicatedtime p

7、oints. After incubation of cells for the indicated periods, cells are harvested 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Sanches M, et al. Structure and mechanism of action of the hydroxy-aryl-aldehyde class of IRE1 endoribonuclease inhibitors. NatCommun. 2014 Aug 28;5:4202.McePdfHeightCaution: Product has not been fully validated for medical applications.For research