Description
Brivanib (BMS-540215) can potently inhibit VEGFR-2, FLK-1, VEGFR-1, and FGFR-1 with IC50 of 25 nM, 89 nM, 380 nM, and 148 nM.
Storage
2 years at -20 centigrade
Targets
VEGFR-2, FLK-1, VEGFR-1, FGFR-1
Molecular Formula
C19H19FN4O3
Chemical Name
(R)-1-(4-(4-fluoro-2-methyl-1H-indol-5-yloxy)-5-methylpyrrolo[1,2-f][1,2,4]triazin-6-yloxy)propan-2-ol
Solubility
DSMO 74 mg/mL Water
In vitro
Brivanib (BMS-540215) can potently inhibit VEGFR-2, FLK-1, VEGFR-1, and FGFR-1 with IC50 of 25 nM, 89 nM, 380 nM, and 148 nM. Brivanib showed good brain penetration in rats consistent with its high intrinsic permeability and lack of active efflux in Caco-2 cells. The oral bioavailability of brivanib varied among species and showed dissolution rate-limited absorption even when combined with organic co-solvents. The clearance of brivanib in humans is anticipated to be low to intermediate, while its volume of distribution is expected to be high.
In vivo
In BDC rats and monkeys, brivanib alaninate was rapidly and completely converted via hydrolysis to brivanib in vivo. In plasma from animals and humans, brivanib was a prominent circulating component. Administration of brivanib as brivanib alaninate allowed completely aqueous vehicles, and an improvement in the oral bioavailability (55-97%) was observed. The minimum efficacious dose of brivanib alaninate was determined to be 60 mg/kg per day.
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