Brivanib (BMS-540215)

Catalog No.S1084 Batch:S108402

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Technical Data

Formula

C19H19FN4O3
Molecular Weight 370.38 CAS No. 649735-46-6
Solubility (25°C)* In vitro DMSO 74 mg/mL (199.79 mM)
Ethanol 3 mg/mL (8.09 mM)
Water Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

Preparing Stock Solutions

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 Assay:[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 Study:[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.

Customer Product Validation

, , Dr. Yong-Weon Yi from Georgetown University Medical Center.

Data from [Data independently produced by , , Eur J Cancer. 2016, 61:20-28.]

Selleck's Brivanib (BMS-540215) has been cited by 12 publications

The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions [ Stem Cells Transl Med, 2023, szad049] PubMed: 37616262
The Antioxidant TEMPOL Protects Human Hematopoietic Stem Cells From Culture-Mediated Loss of Functions [ Stem Cells Transl Med, 2023, 12(10):676-688] PubMed: 37616262
Phosphate-induced activation of VEGFR2 leads to caspase-9-mediated apoptosis of hypertrophic chondrocytes [ iScience, 2023, 26(9):107548] PubMed: 37636062
Phosphate-induced activation of VEGFR2 leads to caspase-9-mediated apoptosis of hypertrophic chondrocytes [ iScience, 2023, 26(9):107548] PubMed: 37636062
Phosphate-induced activation of VEGFR2 leads to caspase-9-mediated apoptosis of hypertrophic chondrocytes [ iScience, 2023, 26(9):107548] PubMed: 37636062
Brivanib, a multitargeted small-molecule tyrosine kinase inhibitor, suppresses laser-induced CNV in a mouse model of neovascular AMD. [ J Cell Physiol, 2020, 235(2):1259-1273] PubMed: 31270802
Brivanib Exhibits Potential for Pharmacokinetic Drug-Drug Interactions and the Modulation of Multidrug Resistance through the Inhibition of Human ABCG2 Drug Efflux Transporter and CYP450 Biotransformation Enzymes. [ Mol Pharm, 2019, 16(11):4436-4450] PubMed: 31633365
Targeting FGFR2 with alofanib (RPT835) shows potent activity in tumour models [Tsimafeyeu I, et al. Eur J Cancer, 2016, 61:20-8] PubMed: 27136102
Antiangiogenic Activity of Alofanib, an Allosteric Inhibitor of Fibroblast Growth Factor Receptor 2. [Khochenkov DA, et al. Bull Exp Biol Med, 2015, 160(1):84-7] PubMed: 26597690
Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer [Nadauld LD, et al. Genome Biol, 2014, 15(8):428] PubMed: 25315765

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