6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline

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.

The Uses of 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline

SB-525334 is a potent activin receptor-like kinase (ALK5)/ type I TGFβ-receptor kinase inhibitor with IC50 = 14.3 nM.

The Uses of 6-[2-tert-Butyl-5-(6-methyl-pyridin-2-yl)-1H-imidazol-4-yl]-quinoxaline

SB-525334 was used to study TGFβ1-mediated human trophoblast differentiation.⁷

What are the applications of Application

TGF-β RI Kinase Inhibitor VIII is a potent ATP-competitive inhibitor against receptor TbR-I/ALK5

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