Brivanib (BMS-540215)

Catalog No.S1084

For research use only.

Brivanib is an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM, moderate potency against VEGFR-1 and FGFR-1, but >240-fold against PDGFR-β. Phase 3.

Brivanib (BMS-540215) Chemical Structure

CAS No. 649735-46-6

Selleck's Brivanib (BMS-540215) has been cited by 7 Publications

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Biological Activity

Description Brivanib is an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM, moderate potency against VEGFR-1 and FGFR-1, but >240-fold against PDGFR-β. Phase 3.
Targets
VEGFR2 [1] Flk1 [1] FGFR1 [1] VEGFR1 [1]
25 nM 89 nM 148 nM 380 nM
In vitro

Brivanib also inhibits VEGFR1 and FGFR-1 with IC50 of 0.38 μM and 0.148 μM. Brivanib is not sensitive to PDGFRβ, EGFR, LCK, PKCα or JAK-3 with IC50 all above 1900 nM. Brivanib could inhibit the proliferation of VEGF-stimulated HUVECs with IC50 of 40 nM, compared to 276 nM in FGF-stimulated HUVECs. On the other hand, Brivanib exhibits low activity to tumor cell lines. [1]

In vivo Brivanib displays antitumor activities in H3396 xenograft in athymic mice. At a dose of 60 and 90 mg/kg (p.o.), Brivanib completely inhibits the tumor growth, with TGI of 85% and 97%, respectively. [1] Moreover, Brivanib significantly suppresses tumor growth in Hepatocellular carcinoma (HCC) xenografts, which due to the decrease in phosphorylation of VEGFR2. The results show that the tumor weights in 06-0606 xenograft mice are 55% and 13%, compared with the controls at a dose of 50 mg/kg and 100 mg/kg. Brivanib is suggested to be efficient in treatment of HCC. [2]

Protocol (from reference)

Kinase Assay:[1]
  • In Vitro Kinase Assays:

    Recombinant proteins containing tyrosine kinases are expressed as GST fusion proteins using baculovirus expression vector system in Sf9 cells. All enzymes are stored at -80 °C. Brivanib is dissolved in DMSO and diluted by water/10% DMSO. The VEGFR2 kinase solution is composed by 8 ng GST-VEGFR2 enzyme, 75 μg/mL substrate, 1 μM ATP, and 0.04 μCi [γ-33P]-ATP in 50 μL buffer: 20 mM Tris (pH 7.0), 25 μg/mL BSA, 1.5 mM MnCl2, 0.5 mM dithiothreitol). Flk-1 kinase solution is composed by 10 ng GST-Flk-1 enzyme, 75 μg/mL substrate, 1 μM ATP, and 0.04 μCi [γ-33P]-ATP in 50 μL buffer: 20 mM Tris, pH 7.0, 25 μg/mL BSA, 4 mM MnCl2, 0.5 mM dithiothreitol). The reactions are incubated for 1 hour at 27 °C and terminated with cold trichloroacetic acid (TCA) to a final concentration of 15%. These TCA precipitates are collected onto unifilter plates and quantitated by liquid scintillation counter.

Cell Research:[1]
  • Cell lines: VEGF or FGF stimulated HUVECs
  • Concentrations: ~ 10 μM
  • Incubation Time: 48 hours
  • Method: The cells are stimulated by VEGF or FGF at a concentration of 8 or 80 ng/mL. These cells are seeded in 96 well plates at a density of 2 × 103 and incubated for 24 hours. Brivanib at various dilutions are added to the cells for another 48 hours. Then 0.5 μCi of [3H] thymidine is added for 24 hours. After that the incorporated tritium is quantified using a β-counter.
Animal Research:[1]
  • Animal Models: H3396 xenografts in athymic mice
  • Dosages: 60 mg/kg (orally) or 10 mg/kg (intravenously)
  • Administration: Administered via oral or i.v.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 370.38
Formula

C19H19FN4O3

CAS No. 649735-46-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OCC(C)O)C

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Clinical Trial Information

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT03895788 Unknown status Drug: niraparib|Drug: Brivanib Ovarian Cancer Hunan Cancer Hospital January 14 2019 Phase 1
NCT01540461 Completed Drug: Brivanib Hepatocellular Carcinoma Bristol-Myers Squibb March 2012 Phase 1
NCT01108705 Terminated Drug: Brivanib|Drug: Placebo Carcinoma Hepatocellular Bristol-Myers Squibb May 2010 Phase 3
NCT01046864 Completed Drug: 5-FU|Drug: Leucovorin|Drug: Irinotecan|Drug: Brivanib Gastro-Intestinal Cancer Bristol-Myers Squibb February 2010 Phase 1
NCT00858871 Completed Drug: Brivanib|Drug: Placebo|Drug: Sorafenib Hepato Cellular Carcinoma (HCC) Bristol-Myers Squibb May 2009 Phase 3

(data from https://clinicaltrials.gov, updated on 2022-01-17)

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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