ODM-203

Research use only, not for human use.

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

ODM-203 a Selective Inhibitor of FGFR and VEGFR Shows Strong Antitumor Activity and Induces Antitumor Immunity.(In Vitro):ODM-203 (eight-dose concentration series up to 3 μM; 96 h) potently inhibits FGFR signaling and proliferation in several FGFR-dependent cell lines.ODM-203 (eight-dose concentration series up to 3 μM; 10 days) inhibits endothelial tubule formation.ODM-203 (1, 10, 100, 1000 nM; 1 h) inhibiting FGFR and VEGFR cellular signaling in HUVEC cells.(In Vivo):ODM-203 (20, 40 mg/kg; p.o.; single daily for 21 days) inhibits FGFR phosphorylation and tumor growth in several FGFR-dependent xenografts by suppressing FGFR signaling in tumors.ODM-203 (7, 20, 40 mg/kg; p.o.; single daily for 21 days) shows strong anti-tumor activity in a VEGFR-dependent angiogenic orthotopic syngenic model (Renca) and suppresses angiogenesis.ODM-203 (20, 40 mg/kg; p.o.; single daily for 5 days) activates immune response in the tumor microenvironment.

ODM-203 (eight-dose concentration series up to 3 μM; 96 h) potently inhibits FGFR signaling and proliferation in several FGFR-dependent cell lines.ODM-203 (eight-dose concentration series up to 3 μM; 10 days) inhibits endothelial tubule formation.ODM-203 (1, 10, 100, 1000 nM; 1 h) inhibiting FGFR and VEGFR cellular signaling in HUVEC cells. Cell Viability AssayCell Line:H1581 (ATCC-CRL-5878), SNU16 (ATCC-CRL-5974) and RT4 (HTB2) cells Concentration:Eight-dose concentration series up to 3 μM Incubation Time:96 h Result:Suppressed cell proliferation in a dose-dependent manner in H1581 (IC50=104 nM), SNU16 (IC50=132 nM) and RT4 cells (IC50=192 nM).Cell Viability Assay Cell Line:HUVECs and human umbilical vein endothelial cells (co-culture)Concentration:Eight-dose concentration series up to 3 μM Incubation Time:10 days (media and test agents were replaced every 2-3 days )Result:Inhibited endothelial tubule formation in a dose-dependent manner at non-toxic concentrations with an IC50 value of 33 nM.Western Blot Analysis Cell Line:HUVEC cells Concentration:1, 10, 100, 1000 nM Incubation Time:1 h Result:Suppressed both FGFR and VEGFR signaling.

ODM-203 (20, 40 mg/kg; p.o.; single daily for 21 days) inhibits FGFR phosphorylation and tumor growth in several FGFR-dependent xenografts by suppressing FGFR signaling in tumors.ODM-203 (7, 20, 40 mg/kg; p.o.; single daily for 21 days) shows strong anti-tumor activity in a VEGFR-dependent angiogenic orthotopic syngenic model (Renca) and suppresses angiogenesis.ODM-203 (20, 40 mg/kg; p.o.; single daily for 5 days) activates immune response in the tumor microenvironment. Animal Model:Athymic Nude-Foxn1nu female mice (9-week-old; subcutaneous xenograft models).Dosage:20, 40 mg/kg Administration:Oral administration; single daily for 21 days.Result:Significantly inhibited tumour growth for 21 consecutive days.Showed tumor growth inhibition (TGI) in RT4 xenografts was 37% and 92% with dosage of 20 and 40 mg/kg, respectively.Animal Model:Male balb/c mice (8-week-old; orthotopic renca syngenic model).Dosage:7, 20, 40 mg/kg Administration:Oral administration; single daily for 21 days.Result:Showed tumor growth inhibition were 39%, 58% and 75% for dosage of 7, 20 and 40 mg/kg, respectively.Inhibited formation of lung metastasis, and suppressed angiogenesis.Animal Model:Male balb/c male mice (5 to 7-week-old; renca subcutaneous tumor model).Dosage:20, 40 mg/kg Administration:Oral administration; single daily for 5 days.Result:Resulted in an increase in the percentage of total and CD4 T cells.Decreased the expression of immune check points PD-1 and PD-L1 and increased IFN-γ expression on both CD8 T cells and NK cells.

——

Angiogenesis

FGFR

FGFR|VEGFR

Cancer

Solid tumours

1430723-35-5

505.54

C26H21F2N5O2S

>98% (HPLC)

In Vitro:?DMSO : 66.67 mg/mL (131.88 mM)

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

N-(2'4'-Difluoro-5-(5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-[11'-biphenyl]-3-yl)cyclopropanesulfonamide

(-20℃)

With Ice Pack

≥ 2 years