| Identification | Back Directory | [Name]
6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline | [CAS]
356559-20-1 | [Synonyms]
SB522334
SB-525334
SB 525334, >=98%
TGF-β RI Kinase Inhibitor VIII
6-[2-tert-butyl-4-(6-methyl-2-pyridyl)-4H-imidazol-5-yl]quinoxaline
6-(2-tert-butyl-4-(6-methylpyridin-2-yl)-1H-imidazol-5-yl)quinoxaline
6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline
6-[2-(1,1-Dimethylethyl)-5-(6-methyl-2-pyridinyl)-1H-imidazol-4-yl]quinoxaline
SB525334 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline
6-[2-(1,1-Dimethylethyl)-5-(6-methyl-2-pyridinyl)-1H-imidazol-4-yl]quinoxaline SB 525334
SB 525334 6-[2-(1,1-Dimethylethyl)-5-(6-methyl-2-pyridinyl)-1H-imidazol-4-yl]quinoxaline | [Molecular Formula]
C21H21N5 | [MDL Number]
MFCD11045307 | [MOL File]
356559-20-1.mol | [Molecular Weight]
343.44 |
| Chemical Properties | Back Directory | [Melting point ]
159 °C | [Boiling point ]
540.5±45.0 °C(Predicted) | [density ]
1.191 | [storage temp. ]
2-8°C | [solubility ]
DMSO: ≥20mg/mL | [form ]
Yellow solid | [pka]
10.24±0.10(Predicted) | [color ]
yellow | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. | [InChIKey]
DKPQHFZUICCZHF-UHFFFAOYSA-N |
| Hazard Information | Back Directory | [Uses]
SB-525334 is a potent activin receptor-like kinase (ALK5)/ type I TGFβ-receptor kinase inhibitor with IC50 = 14.3 nM.
| [Description]
SB-525334 is a potent inhibitor of the TGF-β receptor 1 (TGF-β R1, ALK5) kinase (IC50 = 14.36 nM).1 It is ~4-fold less effective against ALK4 and inactive against ALK2, ALK3, and ALK6.1 SB-525334 blocks TGF-β1-induced phosphorylation and nuclear translocation of SMAD2/3 as well as TGF-β1-directed gene expression.1 It is effective in vivo, preventing puromycin aminonucleoside-induced renal fibrosis and bleomycin-induced pulmonary fibrosis.1,2,3 SB-525334 also modulates carcinogenesis and suppresses the development of pulmonary arterial hypertension in animals.3,4,5 | [Definition]
ChEBI: 6-[2-tert-butyl-5-(6-methyl-2-pyridinyl)-1H-imidazol-4-yl]quinoxaline is a quinoxaline derivative. | [Biochem/physiol Actions]
SB-525334 is a potent activin receptor-like kinase (ALK5)/ type I TGFβ-receptor kinase inhibitor with IC50 = 14.3 nM. | [storage]
Store at -20°C |
| Questions And Answer | Back Directory | [Biological activity]
SB525334 is a potent and selective inhibitor of TGFβ receptor I (ALK5) with IC50 of 14.3 nM in a cell-free assay, 4-fold less potent to ALK4 than ALK5 and inactive to ALK2, 3, and 6. | [In vitro]
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). | [In vivo]
SB 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. | [References]
http://www.selleckchem.com/products/SB-525334.html |
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