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SB525334
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
SB525334图片
CAS NO:356559-20-1
规格:≥98%
包装与价格:
包装价格(元)
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议
250mg电议
500mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)343.42
FormulaC21H21N5
CAS No.356559-20-1
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 68 mg/mL (198.0 mM)
Water: <1 mg/mL
Ethanol: 68 mg/mL (198.0 mM)
Solubility (In vivo)5% DMSO+corn oil: 20 mg/mL
Synonyms

SB 525334; SB-525334; SB525334

Chemical Name: 6-(2-(tert-butyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline

SMILES Code: CC1=CC=CC(C2=C(C3=CC=C4N=CC=NC4=C3)N=C(C(C)(C)C)N2)=N1

Exact Mass: 343.1797

实验参考方法
In Vitro

In vitro activity: SB 525334 shows no inhibition in the enzymes ALK2, 3, and 6, with IC50 values> 10 μM. SB 525334 blocks phosphorylation induced by TGF-β1 and nuclear translocation of Smad2/3 in renal proximal tubule cells. SB 525334 also inhibits the increased mRNA expression levels of plasminogen activator inhibitor-1 (PAI-1) and procollagen α1(I) induced by TGF-β1 in A498 renal epithelial carcinoma cells at 1 μM). SB 525334 (1 μM) attenuates the heightened sensitivity to TGF-β1 exhibited by pulmonary artery smooth muscle cells (PASMCs) from patients with familial forms of idiopathic pulmonary arterial hypertension (PAH).


Kinase Assay: In order to determine the potency of SB 525334, purified GST-tagged kinase domain of ALK5 is incubated with purified GST-tagged full-length Smad3 in the presence of 33P-γATP and different concentrations of SB 525334. The readout is radioactively labeled Smad3. To determine the selectivity of SB 525334, purified GST-tagged kinase domain of ALK2 and ALK4 are incubated with GST-tagged full-length Smad1 and Smad3, respectively, in the presence of different concentrations of SB 525334. IC50 values are calculated.


Cell Assay: RPTE cells are seeded on microscope slides. The following day, the cells are starved for 24 hours to dosing by removal of the serum and epidermal growth factor. Cells are treated with either 10 ng/mL TGF-β1, 1 μM SB 525334, or a combination of both. Slides are pretreated with SB 525334 or starve media for 3 hours prior to a 1-hour incubation at 37 °C with TGF-β1 or starve media. The cells are then fixed and permeabilized. The slides are blocked with BSA, incubated with a mouse anti-Smad2/3 primary antibody followed by an anti-mouse IgG fluorescein secondary antibody. The slides are then viewed in a confocal microscope and nuclear signal intensity is analyzed.

In VivoSB 525334 (10 mg/kg/day) decreases the renal mRNA levels of PAI-1, procollagen α1(I), and procollagen α1(III) in a nephritis-induced renal fibrosis rat model. Furthermore, PAN-induced proteinuria is significantly inhibited by SB 525334 (10 mg/kg/day). SB 525334 may also be efficacious in mesenchymal tumors. SB 525334 (10 mg/kg/day) significantly decreases uterine mesenchymal tumor incidence, multiplicity, and size in Eker rats. SB 525334 significantly reverses pulmonary arterial pressure and inhibits right ventricular hypertrophy in a rat model of PAH. This is revealed by a significant reduction in pulmonary arteriole muscularization induced by monocrotaline (used to induce PAH) after treatment with SB 525334 (3 or 30 mg/kg). In a Bleomycin-induced pulmonary fibrosis mice model, SB 525334 (10 mg/kg or 30 mg/kg) attenuates the histopathological alterations in the lung, and significantly decreased mRNA expression of Type I and III procollagen and fibronectin. SB 525334 also attenuates Smad2/3 nuclear translocation, myofibroblast proliferation, deposition of Type I collagen, and decreases CTGF-expressing cells.
Animal modelBleomycin-induced pulmonary fibrosis in female Eker rats
Formulation & DosageDissolved in 200 mg/L in drinking water; 10mg/kg; oral gavage
References

J Pharmacol Exp Ther. 2005 Jun;313(3):943-51; Am J Pathol. 2009 Feb;174(2):380-9.