Bms 582664

Bms 582664 - Names and Identifiers

Name	Brivanib Alaninate (BMS-582664)
Synonyms	CS-362 BMS582664 Bms582664 BMS 582664 BMS-582664 Bms 582664 Brivanib alaninate Brivanib alaninate BMS-540215 Brivanib Alaninate (BMS-582664) L-Alanine (1R)-2-[[4-[(4-fluoro-2-Methyl-1H-indol-5-yloxy)]-5-Methyl-1H-pyrrolo[2,1-f][1,2,4]triazin-6-yl]oxy]isopropyl ester (2R)-1-({4-[(4-fluoro-2-Methyl-1H-indol-5-yl)oxy]-5-Methylpyrrolo[2,1-f][1,2,4]triazin-6-yl}oxy)propan-2-yl (2S)-2-aMinopropanoate (1R)-2-((4-((4-Fluoro-2-methyl-1H-indol-5-yl)oxy)-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl)oxy)-1-methylethyl L-alanine ester Brivanib alaninate (BMS-582664)
CAS	649735-63-7

Bms 582664 - Physico-chemical Properties

Molecular Formula	C22H24FN5O4
Molar Mass	441.46
Density	1.42±0.1 g/cm3(Predicted)
Solubility	DMSO 88 mg/mL Water <1 mg/mL Ethanol 88 mg/mL
Appearance	Yellow powder.
pKa	16.08±0.30(Predicted)
Storage Condition	-20℃
Use	Brivanib Alaninate (BMS-582664) is a BMS-540215 prodrug and an ATP competitive VEGFR2 inhibitor with an IC50 of 25 nM.
In vitro study	BMS-582664 inhibited VEGF and FGF-stimulated HUVECs proliferation with IC50 of 40 nM and 276 nM, respectively. BMS-582664 (2 μm) significantly inhibited the phosphorylation of SK-HEP1, HepG-2, ERK1/2 and Akt in VEGFR-2 and FGFR-1 cells stimulated by VEGF and bFGF, BMS-582664 alone had no effect on phosphorylation levels of ERK1/2, Akt, VEGFR-2, and FGFR-1 in unstimulated cells. BMS-582664 inhibits CYP2C19, CYP3A4(BFC) and CYP3A4 (BzRes) with IC50 of 2.4 μm, 0.51 μm and 1.6 μm, respectively. BMS-582664 has high solid-state stability (only 0.3% degradation at 50°C during 12 weeks of desiccant placement) and considerable liquid-state stability at pH 6.5.
In vivo study	Mice were treated with BMS-582664 (50 mg/kg) with an AUC of 136 μm×hr and a Cmax of 41 μm. BMS-582664 (60 mg/kg, oral) treated mice, rapidly absorbed, T max of 1 hour, half-life (t 1/2) of 2.7 hours, mean residence time (MRT) 3.6 hours. BMS-582664 Rats (25 mg/kg) were treated with an AUC of 13.4 μm×hr and a Cmax of 6.4 μm. Treatment of athymic mice carrying H3396 tumor xenografts BMS-582664 inhibited tumor growth by 85% and 97% at 60 mg/kg and 90 mg/kg, respectively, this effect was dose-dependent. Treatment of mice carrying patient-derived xenografts 06-0606 at doses of 50 mg/kg and 100 mg/kg BMS-582664 inhibited tumor growth by 55% and 13%, respectively. BMS-582664(60 mg/kg, oral) in mice carrying patient-derived transplanted tumor 06-0606, significantly reduced tumor weight, promoted apoptosis, reduced microvessel density, inhibited cell proliferation, and down regulation of cell cycle. Treatment of non-thymic mice carrying L2987 non-small cell lung cancer xenografts BMS-582664 inhibited tumor growth by 107 and 85% at doses of 80 mg/kg and 97% mg/kg, respectively, this effect was dose-dependent. BMS-582664 (100 mg/kg) inhibited new growth of vascular endothelial cells in two xenograft-bearing mouse models, L2987 and hct116.