356559-20-1 Usage
Description
6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline is a complex organic compound with a unique molecular structure that features a quinoxaline core, an imidazole ring, and various substituents that contribute to its specific properties and potential applications.
Uses
Used in Pharmaceutical Industry:
6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline is used as a potent activin receptor-like kinase (ALK5)/type I TGFβ-receptor kinase inhibitor for the development of therapeutic agents targeting various diseases. Its high specificity and potency make it a valuable compound for research and drug development.
Used in Research Applications:
In the field of cellular and molecular biology, 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline is used to study TGFβ1-mediated human trophoblast differentiation, providing insights into the role of TGFβ signaling in cellular processes and the potential for targeted therapeutic intervention.
Used in Fibrosis Treatment:
6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline demonstrates efficacy in preventing puromycin aminonucleoside-induced renal fibrosis and bleomycin-induced pulmonary fibrosis, making it a potential candidate for the development of anti-fibrotic drugs.
Used in Cancer Research:
6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline also shows promise in cancer research, as it modulates carcinogenesis and suppresses the development of pulmonary arterial hypertension in animals, suggesting potential applications in the development of anti-cancer therapies.
Used in Drug Delivery Systems:
To enhance the bioavailability and therapeutic outcomes of 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline, various drug delivery systems, including organic and metallic nanoparticles, can be employed as carriers for improved delivery and targeting of the compound to specific cells or tissues.
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
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
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.
Check Digit Verification of cas no
The CAS Registry Mumber 356559-20-1 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,5,6,5,5 and 9 respectively; the second part has 2 digits, 2 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 356559-20:
(8*3)+(7*5)+(6*6)+(5*5)+(4*5)+(3*9)+(2*2)+(1*0)=171
171 % 10 = 1
So 356559-20-1 is a valid CAS Registry Number.
InChI:InChI=1/C21H21N5/c1-13-6-5-7-16(24-13)19-18(25-20(26-19)21(2,3)4)14-8-9-15-17(12-14)23-11-10-22-15/h5-12,19H,1-4H3
