ODM-203,98%

产品描述

ODM-203, a Selective Inhibitor of FGFR and VEGFR, Shows Strong Antitumor Activity, and Induces Antitumor Immunity

靶点活性

FGFR1,1nM

FGFR2,16nM

FGFR3,6nM

FGFR4,35 nM

VEGFR1,26nM

VEGFR2,9nM

VEGFR3,5 nM

体外活性

ODM-203 inhibits FGFR and VEGFR family kinases selectively and with equal potency in the low nanomolar range (IC50 6-35 nmol/L) in biochemical assays. In cellular assays, ODM-203 inhibits VEGFR-induced tube formation (IC50 33 nmol/L) with similar potency as it inhibits proliferation in FGFR-dependent cell lines (IC50 50-150 nmol/L).

体内活性

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.

细胞实验

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 Diagnostics) . Briefly, the cell lines were seeded at a density of 75,000 cells/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 10 mmol/L NaF, 1× 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.

动物实验

Athymic Nude-Foxn1nu female mice (9 weeks old; Harlan, the Netherlands) were subcutaneously injected with 1 million H1581, KMS11, RT4, or SNU16 cells in 100 μL of McCoy's 5a modified medium and Matrigel (BD) (1:1). Tumor growth was monitored twice weekly by caliper measurements. Oral treatment with ODM-203 and AZD-4547 was started when the average tumor volume reached 100 mm^3 and continued for 21 days for the RT4 xenograft model (n = 12/group) and 12 days for the SNU16 xenograft model (n = 6/group). Necropsy, and plasma and tumor sampling were carried out 4 hours after the last dosing.Doses for 12.5 mg/kg AZD4547 and 40 mg/kg sorafenib were chosen based on published data. Oral treatment (ODM-203 or AZD4547) was initiated when the average tumor volume reached ≈125 mm^3. Mean tumor volumes were calculated for each treatment group.

分子量

505.54

分子式

C26H21F2N5O2S

CAS

1430723-35-5

溶解度

DMSO: 83.33 mg/mL (164.83 mM), Need ultrasonic

（ < 1 mg/ml refers to the product slightly soluble or insoluble )

储存条件

-20℃

备注

For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.