ODM-203

SKU: orb1299661

Description

ODM-203 is a potent, dual inhibitor of FGFR and VEGFR tyrosine kinases, demonstrating robust antitumor efficacy in preclinical models. Its mechanism extends to stimulating antitumor immunity, making it a valuable tool for cancer research in both in vitro and in vivo studies targeting angiogenesis and tumor microenvironment.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1430723-35-5
• MW: 505.54
• Purity: 99.85% (May vary between batches)
• Formula: C₂₆H₂₁F₂N₅O₂S
• SMILES: Cn1cc(cn1)-c1ccc2n(cnc2c1)-c1cc(NS(=O)(=O)C2CC2)cc(c1)-c1ccc(F)cc1F
• Target: VEGFR,FGFR
• Solubility: DMSO:13 mg/mL (25.72 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (3.96 mM)

Bioactivity

• Target IC50:
  FGFR3:6nM|PDGFRα:35 nM|MINK1:41 nM|FGFR4:35 nM|FGFR1:1nM|SIK3:23 nM|VEGFR1:26nM|MAP4K4:49 nM|FGFR2:16nM|VEGFR3:5 nM|VEGFR2:9nM|RET:8 nM
• In Vivo:
  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.
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• In Vitro:
  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).
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• Cell Research:
  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.
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• Animal Research:
  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.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

inhibit, ODM 203, ODM203, ODM-203, Inhibitor, HUVEC, H1581, FGFR, Fibroblast growth factor receptor, anti-tumor immunity, cancer, RT4, SNU16, Vascular endothelial growth factor receptor, VEGFR

Compound Identifiers

PubChem CID

71554322