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Purity: ≥98%
SB525334 (SB-525334; SB 525334) is a potent and selective inhibitor of TGF-β (transforming growth factor-β) receptor I, ALK5 (activin receptor-like kinase) with potential anti-fibrotic activity. It inhibits TGF-β with an IC50 of 14.3 nM in a cell-free assay. SB525334 is 4-fold less potent to ALK4 than ALK5 and is inactive against ALK2, 3, and 6. In cell-based assays, SB-525334 at the concentration of 1 μM blocked TGF-β1-induced phosphorylation and nuclear translocation of Smad2/3 in renal proximal tubule cells and inhibited TGF-β1-induced increases in plasminogen activator inhibitor-1 (PAI-1) and procollagen alpha1(I) mRNA expression in A498 renal epithelial carcinoma cells.
| ln Vitro |
The study found that SB525334 (1 μM) reduces the proliferation of familial idiopathic pulmonary arterial hypertension (iPAH) pulmonary artery smooth muscle cells (PASMCs) with an IC50 of 295 nM. The effect is observed 15 minutes before stimulating with 0.625 ng/ml of TGF-β1, and evaluation is done after 6 days.
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| ln Vivo |
In a rat model of pulmonary arterial hypertension (PAH), SB525334 (3-30 mg/kg; po; daily from days 17 to 35) dramatically reverses pulmonary arterial pressure[2].
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: PASMC cells Tested Concentrations: 1 μM Incubation Duration: Pre-incubated for 15 minutes (before stimulating with 0.625 ng/ml of TGF-β1), assessed after 6 days Experimental Results: Inhibited TGF-β1-mediated proliferation of familial iPAH PASMCs at an IC50 of 295 nM. |
| Animal Protocol |
Animal/Disease Models: Adult male SD (Sprague-Dawley) rats (MCT rat model of pulmonary hypertension)[2]
Doses: 3, 30 mg/kg Route of Administration: Oral administration; daily from days 17 to 35 Experimental Results: decreased the proportion of fully muscularized vessels to 28% at 3 mg/kg and returned fully muscularized vessel distribution beyond that seen at day 17 and approaching the phenotype observed in saline-exposed controls at 30 mg/kg. |
| References |
[1]. Grygielko ET, et al. Inhibition of gene markers of fibrosis with a novel inhibitor of transforming growth factor-beta type I receptor kinase in puromycin-induced nephritis. J Pharmacol Exp Ther, 2005, 313(3), 943-951.
[2]. Thomas M, et al. ALK5 mediates abnormal proliferation of vascular smooth muscle cells from patients with familial pulmonary arterial hypertension and is involved in the progression of experimental pulmonary arterial hypertension induced by monocrotaline. [3]. Laping NJ, et al. Tumor-specific efficacy of transforming growth factor-beta RI inhibition in Eker rats. Clin Cancer Res, 2007, 13(10), 3087-3899. |
| Molecular Formula |
C21H21N5
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| Molecular Weight |
343.42
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| CAS # |
356559-20-1
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| Related CAS # |
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| SMILES |
CC1=CC=CC(C2=C(C3=CC=C4N=CC=NC4=C3)N=C(C(C)(C)C)N2)=N1
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| Chemical Name |
6-(2-(tert-butyl)-5-(6-methylpyridin-2-yl)-1H-imidazol-4-yl)quinoxaline
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| Synonyms |
SB 525334; SB-525334; SB525334
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9119 mL | 14.5594 mL | 29.1189 mL | |
| 5 mM | 0.5824 mL | 2.9119 mL | 5.8238 mL | |
| 10 mM | 0.2912 mL | 1.4559 mL | 2.9119 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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 PASMCs derived from iPAH patients were plated at equal cell densities in 96-well plates.
Echocardiographic measurement of pulmonary hypertensive parameters in animals.Am J Pathol.2009 Feb;174(2):380-9. |
RV systolic pressure levels (A) and Fulton index measures (RV/LV + S weight ratio) (B) in rats exposed to MCT or saline-negative control.Am J Pathol.20 |
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