Salubrinal - eIF2α Dephosphorylation 抑制剂 - MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemESalubrinalCat. No.: HY-15486CAS No.: 405060-95-9分式: CHClNOS分量: 479.81作靶点: Phosphatase; Autophagy作通路: Metabolic Enzyme/Protease; Autophagy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 m

2、g/mL (104.21 mM)* means soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 2.0842 mL 10.4208 mL 20.8416 mL5 mM 0.4168 mL 2.0842 mL 4.1683 mL10 mM 0.2084 mL 1.0421 mL 2.0842 mL请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Salubrinal是有效的选择性 eIF2 去磷酸

3、化抑制剂。Salubrinal 作为双特异性磷酸酶 2 (Dusp2) 抑制剂，抑制抗胶原蛋抗体诱导的关节炎 2。IC50 & Target IC50: 1.7 M (PP1) 1体外研究Salubrinal, a recently identified PP1 inhibitor capable to protect against endoplasmic reticulum (ER) stress in1/3 Master of Small Molecules 您边的抑制剂师www.MedChemEvarious model systems, strongly synergized wit

4、h proteasome inhibitors to augment apoptotic death ofdifferent leukemic cell lines. Salubrinal preferentially seems to target the PP1/GADD34 complex, Salubrinal isof interest to examine whether the effect of Salubrinal could also be recapitulated by another inhibitor of thisphosphatase. For this pur

5、pose cantharidin, wis selected, which is less toxic than okadaic acid, but which alsoblocks PP1 (IC50=1.7 M) activities 1.体内研究 Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eukaryotic translation initiation factor 2alpha (eIF2). Salubrinal significantly suppresses inflammati

6、on of the paws of CAIA mice. For instance, theclinical scores are 1.941.7 (placebo) and 0.310.6 (Salubrinal) on day 6; and 4.633.4 (placebo) and1.091.6 (Salubrinal) on day 12. Consistent with the clinical scores, the thickening of the paws is alsoreduced in the Salubrinal-treated group. Furthermore,

7、 Salubrinal reduces the histological scores from1.471.10 (N=16; placebo) to 0.590.64 (N=16; Salubrinal) (p=0.01) 2.PROTOCOLKinase Assay 1 Phosphatase activities are determined on immunoprecipitates of the phosphatases. Briefly, 2106 K562 cellsare treated for 18 hr with Salubrinal (20 M), PSI (10 nM)

8、, the combination of both drugs or okadaic acid (100nM). After washing with PBS, cells are lysed for 15 min on ice either in PP1LB (for determination of PP1-activity; 20 mM Tris-HCl, pH 7.5, 1% Triton X-100, 10% glycerol, 132 mM NaCl, Roche complete proteaseinhibitor ) or in RIPA (for PP2A), supplem

9、ented with Roche complete protease inhibitor). Cell lysatescontaining 500 g (PP1) or 300 g (PP2A) protein are immunoprecipitated overnight at 4C with 2-3 g ofthe appropriate antibodies and then incubated with Protein A-Sepharose. Immunoprecipitates are washedthree times in lysis buffer, followed by

10、resuspension in phosphatase assay buffer (PP2A: 20 mM Tris-HCl,pH7.5, 0.1 mM CaCl2; PP1: 50 mM Tris HCl pH 7.0, 0.2 mM MnCl2, 0.1 mM CaCl2, 125 g/mL BSA, 0.05%Tween 20), supplemented with 100 M 6,8-difluoro-4-methyl-umbelliferyl phosphate (DiFMUP). Precipitatesare allowed to react with substrate for

11、 1 hr at 37C on an Eppendorf Thermoshaker, centrifuged and DiFMUfluorescence is measured on a BioTek Lambda Fluoro 320 microplate reader (360 nmex/460 nmem).Phosphatase activities are given as percent change relative to the control (DMSO treated cells) 1.MCE has not independently confirmed the accur

12、acy of these methods. They are for reference only.Cell Assay 1 Cellular viability is assessed by the WST-1 colorimetric assay. Assays are performed on 96 well plates with2104 K562 cells/well in triplicate with Salubrinal concentrations ranging from 5-75 M (total volume of 200L, 18 hrs). Untreated ce

13、lls served as negative control sample 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 2Administration 2 Using Balb/c female mice (nine weeks old), CAIA is induced by intravenous injection of a 2 mg cocktail ofArthritoMAb antibodies on day

14、0 followed by intraperitoneal injection of 100 g LPS on day 3. Mice arerandomly divided into a placebo group and a Salubrinal-treated group. Salubrinal (2.0 mg/kg) is intravenouslyadministered daily from day 0, while a solvent (49.5% PEG 400 and 0.5% Tween 80 in PBS) is administeredto the placebo gr

15、oup.MCE has not independently confirmed the accuracy of these methods. They are for reference only.2/3 Master of Small Molecules 您边的抑制剂师www.MedChemE户使本产品发表的科研献 Cancer Biol Med. 2019 Mar. Cancer Biol Med. 2019 Feb; 16(1): 3854.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Drexler HC. Synergistic Apoptosis Induction in Leukemic Cells by the Phosphatase Inhibitor Salubrinal and Proteasome Inhibitors. PLoSOne. 2009;4(1):e4161.2. Hamamura K, et al. Salubrinal acts as a Dusp2 inhibitor and suppresses inflammation in anti-collagen antibody-induced arthri