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Brivanib Alaninate (BMS-582664) VEGFR inhibitor

Name: Brivanib Alaninate (BMS-582664)
Brand: Selleck Chemicals
SKU: S1138
Availability: InStock
Rating: 5 (2 reviews)

Cat.No.S1138

Brivanib alaninate (BMS-582664) is the prodrug of BMS-540215, an ATP-competitive inhibitor against VEGFR2 with IC50 of 25 nM.

Chemical Structure

Molecular Weight: 441.46

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

Quality Control

Batch: Purity: 99.85%

99.85

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	441.46	Formula	C₂₂H₂₄FN₅O₄	Storage (From the date of receipt)	3 years-20°Cpowder
CAS No.	649735-63-7	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)OC(=O)C(C)N)C

Solubility

In vitro
Batch:

DMSO : 88 mg/mL (199.33 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 88 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	0.5% methylcellulose 1 0.2% Tween 80 Validated by Selleck labs. Should you need adjustments to this formulation, contact our sales team for custom testing.	10.000mg/ml (22.65mM)	Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose+0.2% Tween 80 clear solution, and mix evenly to make it a uniform suspension. The mixed solution should be used immediately for optimal results.
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.

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

Features	Alanine prodrug of BMS-540215.
Targets/IC₅₀/Ki	VEGFR2 ^[1] 25 nM Flk1 ^[1] 89 nM FGFR1 ^[1] 148 nM VEGFR1 ^[1] 380 nM
In vitro	Brivanib Alaninate (BMS-582664) inhibits VEGF-stimulated and FGF-stimulated proliferating of HUVECs with IC50 of 40 nM and 276 nM. ^[1] This compound (2 μM) significantly inhibits VEGFR2, FGFR1, ERK1/2 and Akt phosphorylation in VEGF- and bFGF-stimulated SK-HEP1 cells and HepG-2 cells, while it alone has little effect on levels of phosphorylated ERK1/2, Akt, VEGFR2, and FGFR1 in nonstimulated cells. ^[2] It inhibits CYP2C19, CYP3A4(BFC) and CYP3A4 (BzRes) with IC50 of 2.4 μM, 0.51 μM and 1.6 μM, respectively. Additionally, it exhibits high solid state stability (only 0.3% degradation at 50℃ with desiccant over a period of 12 weeks) and acceptable solution state stability up to pH 6.5. ^[3]
Kinase Assay	Kinase inhibition assays
Kinase Assay	For the VEGFR2, Flk1 and FGFR1 kinase assays, Brivanib Alaninate (BMS-582664) is dissolved in DMSO and diluted with water/10% DMSO to a final DMSO concentration of 2%. The kinase reactions consists of 8 ng of enzymes with GST tag, 75 μg/mL substrate, 1 μM ATP, and 0.04 μCi [γ-³³P]ATP in 50 μL total reaction volume (kinase buffer: 20 mM Tris, pH 7.0, 25 μg/mL BSA, 1.5 mM MnCl₂, 0.5 mM dithiothreitol). In all cases, the reactions are incubated for 60 min at 27℃ and terminated with the addition of cold trichloroacetic acid (TCA) to a final concentration of 15%. The percent inhibition from the kinase assays is determined by nonlinear regression analyses, and data are reported as the inhibitory concentration required to achieve 50% inhibition relative to control reactions (IC50).
In vivo	Brivanib Alaninate (BMS-582664) (50 mg/kg) results in AUC of 136 μM×hr and C_max of 41 μM in mouse. This compound (60 mg/kg, orally) is rapidly absorbed with T_max of 1 hour, a favorable half-life (t_1/2) of 2.7 hours and mean residence time (MRT) of 3.6 hours in mouse. It (25 mg/kg) results in AUC of 13.4 μM×hr and Cmax of 6.4 μM in rat. BMS-582664 dose-dependently inhibits the growth of established tumors with tumor growth inhibition of 85% and 97% at dose of 60 mg/kg and 90 mg/kg in H3396 xenografts athymic mice. ^[1] It inhibits the growth rate of tumors in mice with patient-derived xenograft line 06-0606 by 55% and 13% at dose of 50 mg/kg and 100 mg/kg. This compound (60 mg/kg, orally) significantly reduces tumor weight at sacrifice, increases apoptosis, reduces microvessel density, inhibits of cell proliferation, and down-regulates cell cycle regulators in mice with patient-derived xenograft line 06-0606. ^[2] It dose-dependently inhibits the growth of established tumors with tumor growth inhibition of 85% and 97% at dose of 80 mg/kg and 107 mg/kg in a L2987 nonsmall cell lung tumor xenografts assay in athymic mice. ^[3] BMS-582664 (100 mg/kg) significantly modulates tyrosine kinase receptor 1 (Tie-1), collagen type IV alpha1 (Col4a1), complement component 1, q subcomponent receptor 1 (C1qr1), angiotensin receptor-like 1 (Agtrl1), and vascular endothelial-cadherin (Cdh5) in L2987 nonsmall cell lung tumor xenografts assay in athymic mice. It (100 mg/kg) inhibits the new growth of endothelial cells in two xenografts mouse models, L2987 and HCT116. ^[4]
References	[1] https://pubmed.ncbi.nlm.nih.gov/16570908/ [2] https://pubmed.ncbi.nlm.nih.gov/18829493/ [3] https://pubmed.ncbi.nlm.nih.gov/18288793/ [4] https://pubmed.ncbi.nlm.nih.gov/17638901/

Applications

Methods	Biomarkers	PMID
Western blot	VEGFR2 / p-VEGFR2 / ER / p-ER / β-Actin	20303261
Growth inhibition assay	MCF-7 E2 tumors	20303261
IHC	H&E staining in necrotic tissue	20303261

Clinical Trial Information

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

NCT Number	Recruitment	Conditions	Sponsor/Collaborators	Start Date	Phases
NCT00390936	Completed	Solid Tumors	Bristol-Myers Squibb	October 2007	Phase 1
NCT00435669	Completed	Tumors	Bristol-Myers Squibb	September 2007	Phase 1
NCT00437424	Completed	Carcinoma Hepatocellular	Bristol-Myers Squibb	July 2007	Phase 1
NCT00437437	Completed	Tumors	Bristol-Myers Squibb	May 2000	Phase 1

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