ChemicalBook CAS DataBase List 1430723-35-5

1430723-35-5

Name	ODM203
CAS	1430723-35-5
Molecular Formula	C26H21F2N5O2S
MDL Number	MFCD32062783
Molecular Weight	505.54
MOL File	1430723-35-5.mol

Chemical Properties

Boiling point	732.4±70.0 °C(Predicted)
density	1.48±0.1 g/cm3(Predicted)
storage temp.	Store at -20°C
solubility	DMSO : 66.67 mg/mL (131.88 mM; Need ultrasonic)
form	A crystalline solid
pka	7.88±0.20(Predicted)
color	White to yellow

Safety Data

Symbol(GHS)	GHS07
Signal word	Warning
Hazard statements	H302-H315-H319-H335
Precautionary statements	P261-P305+P351+P338

Hazard Information

Uses

ODM-203 is an orally active and selective FGFR/VEGFR inhibitor with IC50 values of 6, 11, 16, 5, 9, 26 and 35 nM for FGFR3/1/2 and VEGFR3/2/1/4, respectively. ODM-203 has strong anti-tumour activity and activates immune responses in the tumour microenvironment[1].

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^[1].
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^[1].
ODM-203 (20, 40 mg/kg; p.o.; single daily for 5 days) activates immune response in the tumor microenvironment^[1].

Animal Model:	Athymic Nude-Foxn1nu female mice (9-week-old; subcutaneous xenograft models)^[1].
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)^[1].
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)^[1].
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.

IC 50

FGFR1: 11 nM (IC₅₀); FGFR2: 16 nM (IC₅₀); FGFR3: 6 nM (IC₅₀); FGFR4: 35 nM (IC₅₀); VEGFR1: 26 nM (IC₅₀); VEGFR2: 9 nM (IC₅₀); VEGFR3: 5 nM (IC₅₀); DDR1: 6 nM (IC₅₀); RET: 8 nM (IC₅₀); SIK3: 23 nM (IC₅₀); PDGFRa: 35 nM (IC₅₀); MINK1: 41 nM (IC₅₀); MAP4K4: 49 nM (IC₅₀)

storage

Store at -20°C

References

[1] Holmstr?m TH, et al. ODM-203, a Selective Inhibitor of FGFR and VEGFR, Shows Strong Antitumor Activity, and Induces Antitumor Immunity. Mol Cancer Ther. 2019 Jan;18(1):28-38. DOI:10.1158/1535-7163.MCT-18-0204

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