ODM-203 Inhibitor

Solid. Powder

98.77%

Store at -20 degree C for 3 years powder
-80 degree C for 2 years in solvent

505.54

DMSO: 83.33mg/mL (164.83mM) Need ultrasonic
(<1mg/ml refers to the product slightly soluble or insoluble)

C26H21F2N5O2S

Cn1cc(-c2ccc3c(c2)ncn3-c2cc(NS(=O)(=O)C3CC3)cc(-c3ccc(F)cc3F)c2)cn1

1430723-35-5

FGFR1: ic50 1nM
FGFR2: ic50 16nM
FGFR3: ic50 6nM
FGFR4: ic50 35nM
VEGFR1: ic50 26nM
VEGFR2: ic50 9nM
VEGFR3: ic50 5nM

Inhibition of FRS2 Tyrosine 196 phosphorylation by ODM-203 in FGFR-dependent cell lines was measured using an MSD 96-well multiarray Phospho-FRS2 Tyr196 assay (MesoScale). Briefly, the cell lines were seeded at a density of 75,000cells/well on poly-d-lysine-coated 96-well plates in the cell culture media. The cells were allowed to attach overnight and subsequently treated with the vehicle (0.5% DMSO) or increasing concentrations of ODM-203 for 20 minutes. The cell culture media were aspirated and the cells lysed in MSD Tris Lysis Buffer supplemented with 10mMol/L NaF, 1x phosphatase inhibitor cocktail 2 and 3 and Complete Protease Inhibitor Cocktail. The electrochemiluminescence signal was detected with a SECTOR Imager 2400 plate reader coupled to a CCD camera. Data were expressed as percentages of vehicle control values and analyzed with GrapPadPrism 7.03. Each test concentration was studied at least in triplicate and inhibition percentages were calculated for the parallel samples. Average IC50 values were calculated from two independent experiments.

In vivo, ODM-203 shows strong antitumor activity in both FGFR-dependent xenograft models and in an angiogenic xenograft model at similar well-tolerated doses.

Angiogenesis; Tyrosine Kinase/Adaptors