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Brivanib (BMS-540215)

Name: Brivanib (BMS-540215)
Brand: Selleck Chemicals
SKU: S1084
Rating: 5 (7 reviews)

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

2 Customer Reviews

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VEGFR Signaling Pathway Map

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.

References

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight	370.38
Formula	C₁₉H₁₉FN₄O₃
CAS No.	649735-46-6
Storage	3 years	-20°C	powder
Storage	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)

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