Cas No.: | 658084-23-2 |
Chemical Name: | (Z)-N-(3-chlorophenyl)-3-((3,5-dimethyl-4-(1-methylpiperazine-4-carbonyl)-1H-pyrrol-2-yl)methylene)-N-methyl-2-oxoindoline-5-sulfonamide |
Synonyms: | SU-11274,PKI-SU11274,SU 11274 |
SMILES: | N1C2=C(C=C(S(N(C3=CC=CC(Cl)=C3)C)(=O)=O)C=C2)/C(=C/C2=C(C)C(C(N3CCN(C)CC3)=O)=C(C)N2)/C1=O |
Formula: | C28H30CIn5O4S |
M.Wt: | 568.09 |
Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
Description: | SU11274 is a selective Met inhibitor with IC50 of 10 nM, but has no effects on PGDFRβ, EGFR or Tie2. |
In Vitro: | SU11274 exhibits greater than 50-fold selectivity for Met versus Flk and more than 500 times selectivity versus other tyrosine kinases such as FGFR-1, c-src, PDGFbR, and EGFR. SU11274 inhibits the phosphorylation of key regulators of the PI3K pathway, including AKT, FKHR, or GSK3β. SU11274 treatment inhibits the growth of TPR-MET-transformed BaF3 cells in a dose-dependent manner with IC50 of < 3 μM in the absence of interleukin 3, without growth inhibition of BaF3 cells transformed by other oncogenic tyrosine kinases, including BCR-ABL, TEL-JAK2, TEL-ABL, and TEL-PDGFβR. In addition to cell growth, SU11274 treatment significantly inhibits the migration of BaF3. TPR-MET cells by 44.8% and 80% at 1 μM and 5 μM, respectively. SU11274 inhibits HGF-dependent phosphorylation of Met as well as HGF-dependent cell proliferation and motility with an IC50 of 1-1.5 μM. In H69 and H345 cells which have functional Met receptor, SU11274 inhibits the HGF-induced cell growth with IC50 of 3.4 μM and 6.5 μM, respectively. SU11274 induces G1 cell cycle arrest with cells in G1 phase increased from 42.4% to 70.6% at 5 μM, and induces caspase-dependent apoptosis by 24% at 1 μM[2]. SU11274 inhibits cell viability in c-Met-expressing non-small cell lung cancer (NSCLC) cells with IC50 values of 0.8-4.4 μM, and abrogates hepatocyte growth factor-induced phosphorylation of c-Met and its downstream signaling[3]. |