Brivanib (alaninate)

SKU: orb1305304

Description

Brivanib Alaninate (BMS-582664) is a VEGFR2 kinase inhibitor salt formulated for research. It suppresses tumor angiogenesis and growth by selectively targeting VEGFR2, as demonstrated in studies investigating hepatocellular carcinoma and colorectal cancer models both in vitro and in vivo.

Research Area

Cardiovascular Research, Cell Biology, Signal Transduction

Key Properties

• CAS Number: 649735-63-7
• MW: 441.46
• Purity: 99.46%
• Formula: C₂₂H₂₄FN₅O₄
• SMILES: C[C@H](COc1cn2ncnc(Oc3ccc4[nH]c(C)cc4c3F)c2c1C)OC(=O)[C@H](C)N
• Target: Autophagy,FGFR,VEGFR
• Solubility: Ethanol:82 mg/mL (185.75 mM);10% DMSO+90% Corn Oil:3.3 mg/mL (7.48 mM);DMSO:82 mg/mL (185.75 mM)

Bioactivity

• Target IC50:
  VEGFR2:25 nM|VEGFR1:380 nM|FLK1:89 nM|FGFR1:148 nM
• In Vivo:
  BMS-582664 exhibits high solid stability, with only 0.3% degradation after a 12-cycle period at 50°C in the presence of desiccants and good liquid stability at pH 6.5. At 2 μM concentration, BMS-582664 significantly inhibits the phosphorylation of VEGFR-2, FGFR-1, ERK1/2, and Akt in SK-HEP1 and HepG-2 cells stimulated by VEGF and bFGF, without affecting the phosphorylation levels in unstimulated cells. It also inhibits the proliferation of HUVECs stimulated by VEGF and FGF, with IC50 values of 40 nM and 276 nM, respectively. Furthermore, BMS-582664 inhibits the enzymes CYP2C19, CYP3A4(BFC), and CYP3A4 (BzRes), with IC50 values of 2.4 μM, 0.51 μM, and 1.6 μM, respectively.
• In Vitro:
  In rats, administration of 25 mg/kg BMS-582664 resulted in an area under the curve (AUC) of 13.4 μM×hr and a peak concentration (Cmax) of 6.4 μM. In mice, 50 mg/kg BMS-582664 achieved an AUC of 136 μM×hr and a Cmax of 41 μM. At doses of 50 mg/kg and 100 mg/kg, BMS-582664 inhibited tumor growth rates by 55% and 13%, respectively, in mice bearing patient-derived xenograft tumor 06-0606. Oral administration of 60 mg/kg BMS-582664 significantly reduced tumor weight, promoted apoptosis, decreased microvascular density, inhibited cell proliferation, and downregulated cell cycle regulation in mice with patient-derived xenograft tumor 06-0606. Mice administered 60 mg/kg BMS-582664 orally displayed rapid absorption with a maximum concentration time (Tmax) of 1 hour, a half-life (t1/2) of 2.7 hours, and a mean residence time of 3.6 hours. The growth of H3396 xenograft tumors in athymic mice was dose-dependently inhibited by 60 mg/kg and 90 mg/kg BMS-582664, with tumor growth inhibition rates of 85% and 97%, respectively. Doses of 80 mg/kg and 107 mg/kg BMS-582664 dose-dependently inhibited tumor growth in athymic mice bearing L2987 non-small cell lung cancer xenograft tumors, with tumor growth inhibition rates of 85% and 97%, respectively. At a dose of 100 mg/kg, BMS-582664 inhibited the growth of endothelial cells in two mouse xenograft models (L2987 and HCT116).
• Cell Research:
  Cells are grown in 100 μL of minimal growth medium and 1.0% heat-inactivated fetal bovine serum in 96-well collagen IV coated plates at a density of 2 × 103 per well in a 37 ℃/5% CO2 environment. Twenty-four hours later, serum is adjusted to 10%, and BMS-582664 at various dilutions are added to each well in a final volume of minimal growth media that contains 10% serum. Forty-eight hours later, 0.5 μCi of [3H]thymidine is added in a volume of 20 μL of minimal media for 24 hours. Plates are washed once in PBS. Upon removal of PBS, Trypsin is added to cells which are subsequently harvested onto glass-fiber filters using an automated harvestor. Incorporated tritium is quantified using a β-counter. Dose response curves are generated to determine the IC50 value, which is defined as the concentration of drug required to inhibit 50% of tritium incorporation when compared to untreated serum-stimulated cells.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Brivanib, Brivanib (alaninate), Brivanib Alaninate, BMS 582664, BMS582664, BMS-582664, Autophagy, alaninate, inhibit, Inhibitor, Flk1, FGFR1, Vascular endothelial growth factor receptor, VEGFR2, VEGFR1, VEGFR

Compound Identifiers

PubChem CID

11154925