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Brivanib (BMS-540215) VEGFR inhibitor

Name: Brivanib (BMS-540215)
Brand: Selleck Chemicals
SKU: S1084
Availability: InStock
Rating: 5 (10 reviews)

Cat.No.S1084

Brivanib (BMS-540215) is an ATP-competitive inhibitor with an IC50 of 25 nM against VEGFR2, moderate potency against VEGFR-1 and FGFR-1, but >240-fold against PDGFR-β. It is in Phase 3.

Chemical Structure

Molecular Weight: 370.38

Jump to Mechanism of Action Solubility Chemical Information, Storage & Stability Specificity

Quality Control

Batch: Purity: 99.54%

99.54

Related Targets	EGFR PDGFR FGFR c-Met Src FLT3 HER2 c-Kit Bcr-Abl MEK BTK IGF-1R ALK Trk receptor Syk Axl CSF-1R c-RET FAK Mertk Tie-2 DYRK Tyro3 Ephrin receptor ROS1 Pyk2 RON DDR ACK Fer kinase
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Chemical Information, Storage & Stability

Molecular Weight	370.38	Formula	C₁₉H₁₉FN₄O₃	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	649735-46-6	Download SDF		Storage of Stock Solutions	1 year-80°Cin solvent 1 month-20°Cin solvent
Synonyms	N/A			Smiles	CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OCC(C)O)C

Solubility

In vitro
Batch:

DMSO : 74 mg/mL (199.79 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 3 mg/mL

Water : Insoluble

Molarity Calculator

Mass	Concentration	Volume	Molecular Weight
=	×	×

Dilution Calculator Molecular Weight Calculator

In vivo Batch:
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension	CMC-NA	≥5mg/ml	Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution	5%DMSO 1 40%PEG300 2 5%Tween80 3 50%ddH2O Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	3.700mg/ml (9.99mM)	Taking the 1 mL working solution as an example, add 50 μL of 74 mg/ml clarified DMSO stock solution to 400 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify; then continue to add 500 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results.
Clear solution	5% DMSO 1 95% Corn oil Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	0.525mg/ml (1.42mM)	Taking the 1 mL working solution as an example, add 50 μL of 10.5 mg/ml clear DMSO stock solution to 950 μL of corn oil and mix evenly. The mixed solution should be used immediately for optimal results.

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

Dosage: mg/kg Average weight of animals: g Dosing volume per animal:μL Number of animals:

Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)

% DMSO + % + % Tween 80 + % ddH₂O

%DMSO+ %

Calculation results:

Working concentration: mg/ml;

Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH₂O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Mechanism of Action

Targets/IC₅₀/Ki	VEGFR2 ^[1] 25 nM Flk1 ^[1] 89 nM FGFR1 ^[1] 148 nM VEGFR1 ^[1] 380 nM
In vitro	Brivanib (BMS-540215) inhibits VEGFR1 and FGFR-1 with IC50 values of 0.38 μM and 0.148 μM, respectively. It is not sensitive to PDGFRβ, EGFR, LCK, PKCα or JAK-3, with IC50 values all above 1900 nM. This compound could inhibit the proliferation of VEGF-stimulated HUVECs with an IC50 of 40 nM, compared to 276 nM in FGF-stimulated HUVECs. On the other hand, it exhibits low activity against tumor cell lines. ^[1]
Kinase Assay	In Vitro Kinase Assays
Kinase Assay	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 (BMS-540215) 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.
In vivo	Brivanib (BMS-540215) displays antitumor activities in H3396 xenograft in athymic mice. At a dose of 60 and 90 mg/kg (p.o.), it completely inhibits the tumor growth, with TGI of 85% and 97%, respectively. ^[1] Moreover, this compound significantly suppresses tumor growth in Hepatocellular carcinoma (HCC) xenografts, which is 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. It is suggested to be efficient in treatment of HCC. ^[2]
References	[1] https://pubmed.ncbi.nlm.nih.gov/16570908/ [2] https://pubmed.ncbi.nlm.nih.gov/18829493/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

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

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