5-[2-[4-[2-(Dimethylamino)ethoxy]phenyl]-5-(4-pyridinyl)-1H-imidazol-4-yl]-2,3-dihydro-1H-inden-1-one oxime

Uses

SB 590885 is a potent Raf-B inhibitor.

Definition

ChEBI: (E)-SB-590885 is an N-{5-[2-{4-[2-(dimethylamino)ethoxy]phenyl}-4-(pyridin-4-yl)-1H-imidazol-5-yl]-2,3-dihydro-1H-inden-1-ylidene}hydroxylamine in which the oxime group has E configuration.

Biological Activity

sb590885 is a potent and selective inhibitor of b-raf kinase with ki value of 0.16nm [1].sb590885 is a potent inhibitor of oncogenic b-raf protein kinase with ki value of 0.16nm. it is more potent to inhibit b-raf than c-raf. the ki value of sb590885 for c-raf is 1.72nm. sb590885 is a quite selective inhibitor. it shows no activity against 48 other human kinases such as abl, ampk, ck1, ck2 and erk2. it is found that sb590885 binds to b-raf within the atp-binding pocket and stabilizes the active conformation of b-raf. sb590885 decreases the phosphorylation of erk and shows anti-proliferation only in tumor cells expressing oncogenic b-raf v600e. the normal cells and tumor cells not expressing mutant b-raf have no sensitivity towards sb590885 except the normal melanocytes and primary melanoma cells expressing wild-type b-raf. moreover, sb590885 is also found to decrease the transformed and tumorigenic properties of malignant cells expressing mutant b-raf [1].

in vivo

IC 50

B-Raf: 0.16 nM (Ki); c-Raf: 1.72 nM (Ki)

storage

Store at -20°C

References

[1] king a j, patrick d r, batorsky r s, et al. demonstration of a genetic therapeutic index for tumors expressing oncogenic braf by the kinase inhibitor sb-590885. cancer research, 2006, 66(23): 11100-11105.