|
|
| | 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline Chemical Properties |
| Melting point | 159 °C | | Boiling point | 540.5±45.0 °C(Predicted) | | density | 1.191 | | storage temp. | 2-8°C | | solubility | DMSO: ≥20mg/mL | | pka | 10.24±0.10(Predicted) | | form | Yellow solid | | 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 Codes | Xn | | Risk Statements | 22-36/37/38 | | Safety Statements | 26 | | RIDADR | UN 2811 6.1/PG 3 | | WGK Germany | 3 | | HS Code | 2933.39.6190 |
| | 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline Usage And Synthesis |
| 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 | | Description | SB-525334 is a potent inhibitor of the TGF-β receptor 1 (TGF-β R1, ALK5) kinase (IC50 = 14.36 nM). It is ~4-fold less effective against ALK4 and inactive against ALK2, ALK3, and ALK6. SB-525334 blocks TGF-β1-induced phosphorylation and nuclear translocation of SMAD2/3 as well as TGF-β1-directed gene expression. It is effective in vivo, preventing puromycin aminonucleoside-induced renal fibrosis and bleomycin-induced pulmonary fibrosis. SB-525334 also modulates carcinogenesis and suppresses the development of pulmonary arterial hypertension in animals. | | Uses | SB-525334 is a potent activin receptor-like kinase (ALK5)/ type I TGFβ-receptor kinase inhibitor with IC50 = 14.3 nM. | | Uses | SB-525334 was used to study TGFβ1-mediated human trophoblast differentiation.7 | | Definition | ChEBI: 6-[2-tert-butyl-5-(6-methyl-2-pyridinyl)-1H-imidazol-4-yl]quinoxaline is a quinoxaline derivative. | | Biological Activity | Selective inhibitor of transforming growth factor- β receptor I (ALK5, TGF- β RI) (IC 50 = 14.3 nM). Inhibits TGF- β 1-induced smad2/3 nuclear localisation and TGF- β 1-induced mRNA expression in kidney cells. Attenuates bleomycin-induced pulmonary fibrosis. | | 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 | | References | 1) Grygielko?et al.?(2005),?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.,?313?943
2) Higashiyama?et al. (2007),?Inhibition of activin receptor-like kinase 5 attenuates bleomycin-induced pulmonary fibrosis;? Exp. Mol. Pathol.,?83?39
3) Kim?et al. (2012),?Transforming growth factor beta receptor I inhibitor sensitizes drug-resistant pancreatic cancer cells to gemcitabine;? Anticancer Res.,?32?799 |
| | 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline Preparation Products And Raw materials |
|