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Purity: ≥98%
Brivanib alaninate (formerly BMS-582664) is the alaninate ester form and prodrug of Brivanib, which is an investigational and ATP-competitive inhibitor of VEGFR2 with potential anticancer activity. It exhibits >240-fold selectivity over PDGFR-β but moderate potency against VEGFR-1 and FGFR-1. Its IC50 for VEGFR2 inhibition is 25 nM. Brivanib alaninate is hydrolyzed to become Brivanib. Both in vitro and in vivo antitumor efficaciousness are demonstrated by its strong anti-proliferative activity.
| Targets |
VEGFR2 (IC50 = 25 nM); Flk1 (IC50 = 89 nM); FGFR1 (IC50 = 148 nM); VEGFR1 (IC50 = 380 nM)
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| ln Vitro |
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| ln Vivo |
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| Enzyme Assay |
BMS-582664 is dissolved in DMSO and diluted with water/10% DMSO to a final DMSO concentration of 2% for the VEGFR2, Flk1, and FGFR1 kinase assays. Eight ng of GST-tagged enzymes, 75 μg/mL of substrate, 1 μM ATP, and 0.04 μCi [γ-33P]ATP are included in the 50 μL total reaction volume of the kinase reactions (kinase buffer: 20 mM Tris, pH 7.0, 25 μg/mL BSA, 1.5 mM MnCl2, 0.5 mM dithiothreitol). All reactions are brought to a final concentration of 15% by adding cold trichloroacetic acid (TCA) after they have been incubated for 60 minutes at 27°C. Nonlinear regression analyses are used to calculate the percent inhibition from the kinase assays. The data are presented as the inhibitory concentration needed to achieve 50% inhibition in comparison to control reactions (IC50).
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| Cell Assay |
LX-2 cell viability is assessed using the Cell Counting Kit-8 (CCK-8). HSCs are cultivated in DMEM supplemented with 10% FBS for 24 hours using 96-well plates containing 2,000 cells per well. Subsequently, the cells are starved in serum-free media. Different doses of brivanib are added following a 24-hour fast. Add 5 ng/mL PDGF-BB after 2 hours. After a further 72 hours of incubation, the cells' viability is assessed. Every experiment is run through at least four times in three replicates[3].
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| Animal Protocol |
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| Additional Infomation |
Brivanib alaninate is a carboxylic ester resulting from the formal condensation of the carboxy group of L-alanine with the hydroxy group of brivanib. It is a prodrug of brivanib (BMS-540215), a potent oral dual inhibitor of VEGFR-2 and FGFR-1 (IC50 of 25 nM and 148 nM, respectively) and was in development for the treatment of hepatocellular and colon carcinomas. It has a role as an antineoplastic agent, an EC 2.7.10.1 (receptor protein-tyrosine kinase) inhibitor, a prodrug, an apoptosis inducer, a fibroblast growth factor receptor antagonist and an angiogenesis inhibitor. It is a pyrrolotriazine, an aromatic ether, a fluoroindole, a diether, a carboxylic ester and a L-alanine derivative. It is functionally related to a brivanib.
Brivanib alaninate has been investigated for the treatment of Colorectal Cancer. Brivanib Alaninate is the alaninate salt of a vascular endothelial growth factor receptor 2 (VEGFR2) inhibitor with potential antineoplastic activity. Brivanib strongly binds to and inhibits VEGFR2, a tyrosine kinase receptor expressed almost exclusively on vascular endothelial cells; inhibition of VEGFR2 may result in inhibition of tumor angiogenesis, inhibition of tumor cell growth, and tumor regression. See also: Brivanib (annotation moved to). |
| Molecular Formula |
C22H24FN5O4
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| Molecular Weight |
441.46
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| Exact Mass |
441.181
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| Elemental Analysis |
C, 59.86; H, 5.48; F, 4.30; N, 15.86; O, 14.50
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| CAS # |
649735-63-7
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| Related CAS # |
Brivanib;649735-46-6
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| PubChem CID |
11154925
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| Appearance |
White to brown solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.648
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| LogP |
2.27
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
32
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| Complexity |
660
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| Defined Atom Stereocenter Count |
2
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| SMILES |
FC1=C(C([H])=C([H])C2=C1C([H])=C(C([H])([H])[H])N2[H])OC1C2=C(C([H])([H])[H])C(=C([H])N2N=C([H])N=1)OC([H])([H])[C@@]([H])(C([H])([H])[H])OC([C@]([H])(C([H])([H])[H])N([H])[H])=O
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| InChi Key |
LTEJRLHKIYCEOX-OCCSQVGLSA-N
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| InChi Code |
InChI=1S/C22H24FN5O4/c1-11-7-15-16(27-11)5-6-17(19(15)23)32-21-20-13(3)18(8-28(20)26-10-25-21)30-9-12(2)31-22(29)14(4)24/h5-8,10,12,14,27H,9,24H2,1-4H3/t12-,14+/m1/s1
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| Chemical Name |
[(2R)-1-[4-[(4-fluoro-2-methyl-1H-indol-5-yl)oxy]-5-methylpyrrolo[2,1-f][1,2,4]triazin-6-yl]oxypropan-2-yl] (2S)-2-aminopropanoate
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| Synonyms |
BMS582664; BMS-582664; Brivanib Alaninate; BMS 582664
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.71 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.71 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (4.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 0.5% methylcellulose+0.2% Tween 80: 10mg/mL |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2652 mL | 11.3261 mL | 22.6521 mL | |
| 5 mM | 0.4530 mL | 2.2652 mL | 4.5304 mL | |
| 10 mM | 0.2265 mL | 1.1326 mL | 2.2652 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01267253 | Completed | Other: Laboratory Biomarker Analysis Drug: Brivanib Alaninate |
Cervical Adenocarcinoma Persistent Disease |
Gynecologic Oncology Group | April 4, 2011 | Phase 2 |
| NCT00437437 | Completed | Tumors | Bristol-Myers Squibb | Astellas Pharma Inc | May 2000 | Phase 1 |
| NCT00888173 | Completed | Other: Laboratory Biomarker Analysis Drug: Brivanib Alaninate |
Endometrial Transitional Cell Carcinoma Endometrial Adenocarcinoma |
Gynecologic Oncology Group | July 6, 2009 | Phase 2 |
| NCT00798252 | Completed | Drug: Brivanib alaninate Drug: Paclitaxel |
Advanced Cancer | Bristol-Myers Squibb | March 2009 | Phase 1 |
Effects of brivanib on growth rate of patient-derived HCC xenograft lines 06-0606, 2-1318, and 26-1004. Clin Cancer Res. 2008 Oct 1;14(19):6146-53. |
Effects of brivanib on VEGFR-2 activity, cell proliferation, and apoptosis in HCC xenograft lines 06-0606 (A) and 26-1004 (B). Clin Cancer Res. 2008 Oct 1;14(19):6146-53. |
Effects of brivanibon (A and C) VEGF-induced, bFGF-induced, and (B) IGF-I–induced phosphorylation of VEGFR-2, FGFR, Akt, and ERK1/2 in SK-HEP1 (A and B) and HepG2 (C) cells. Clin Cancer Res. 2008 Oct 1;14(19):6146-53. |
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