YO-01027-Dibenzazepine-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEYO-01027Cat. No.: HY-13526CAS No.: 209984-56-5Synonyms: Dibenzazepine; DBZ分式: CHFNO分量: 463.48作靶点: Notch; -secretase作通路: Neuronal Signaling; Stem Cell/Wnt储存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性数据

2、体外实验 DMSO : 33 mg/mL (71.20 mM)H2O : 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (5.39 mM); Suspended solution; Need ultrasonic2. 请依序添加每种溶剂： 10% DMSO 90% (20% SBE-CD in saline)1/3 Master of Small Molecules 您边的抑制剂师www.MedChemESolubility: 2.5 mg/mL (5.39 mM); Suspended solution; Need ultras

3、onic3. 请依序添加每种溶剂： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (5.39 mM); Clear solutionBIOLOGICAL ACTIVITY物活性 YO-01027 (Dibenzazepine;DBZ)效的-分泌酶抑制剂，裂解Notch和APPL的IC50分别为2.920.22和2.640.30 nM。IC50 & Target IC50: 2.920.22 (Notch), 2.640.30 (APPL) nM 1体外研究 Increasing concentrations of DBZ administered to

4、APPL- or Notch-expressing cells leads to the progressiveaccumulation of APPL CTF fragments and a decrease in NICD production in a strictly dose-dependentmanner 1. The molecular targets of CE and DBZ are the N-terminal fragment of presenilin 1 within the -secretase complex 2.体内研究 DBZ blocks activated

5、 Notch1 signaling in abdominal aortic aneurysm (AAA) tissue from both Ang II-infusedApo E-/- mice and human undergoing AAA repair. DBZ markedly prevents Ang II-stimulated accumulation ofmacrophages and CD4+ T cells, and ERK-mediated angiogenesis, simultaneously reverses Th2 response, invivo 3. Admin

6、istration of DBZ markedly attenuates renal fibrosis and expression of fibrotic markers,including collagen 11/31, fibronectin, and -smoothmuscle actin. DBZ significantly inhibits ureteralobstruction -induced expression of transforming growth factor (TGF)- , phosphorylated Smad 2, and Smad 34.PROTOCOL

7、Cell Assay 1 DBZ (0.1, 1, 2.5, 5, 7.5, 10, 25, 50, 100, 250 nM) are added to the S2 cell medium upon induction of Notch orAPPL expression, 6 h before protein harvesting. For each sample, the same inhibitor is also included at thecorresponding concentration in the lysis buffer for protein extraction

8、and immunoblot analysis 1.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice: Male wild-type (WT) C57BL/6J and Apo E-/- mice are used in the study. Ang II-treated mice areAdministration 3 received an intraperitoneal injection of either saline v

9、ehicle or -secretase inhibitor, dibenzazepine (DBZ) (1mg/kg/d, dissolved in saline) 1 day before mini-pump implantation, and the treatment continued daily for 4weeks. The blood pressure is measured in conscious mice using a computerized tail-cuff system. All miceare anesthetized. The aortic tissues

10、are removed and prepared for further histological and molecular analysis3.MCE has not independently confirmed the accuracy of these methods. They are for reference only.REFERENCES1. Groth C, et al. Pharmacological analysis of Drosophila melanogaster gamma-secretase with respect to differential prote

11、olysis of Notch2/3 Master of Small Molecules 您边的抑制剂师www.MedChemEand APP. Mol Pharmacol. 2010 Apr;77(4):567-74.2. Fuwa H, et al. Divergent synthesis of multifunctional molecular probes to elucidate the enzyme specificity of dipeptidic gamma-secretaseinhibitors. ACS Chem Biol. 2007 Jun 15;2(6):408-18.

12、3. Zheng YH, et al. Notch -secretase inhibitor dibenzazepine attenuates angiotensin II-induced abdominal aortic aneurysm in ApoEknockout mice by multiple mechanisms. PLoS One. 2013 Dec 16;8(12):e83310.4. Xiao Z, et al. The Notch -secretase inhibitor ameliorates kidney fibrosis via inhibition of TGF-/Smad2/3 signaling pathway activation.Int J Biochem Cell Biol. 2014 Oct;55:65-71.McePdfHeightCautio