Brivanib (BMS-540215)

製品コードS1084 バッチS108404

印刷

化学情報

Synonyms

N/A

Storage
(From the date of receipt)

3 years -20°C powder
1 years -80°C in solvent

化学式

C₁₉H₁₉FN₄O₃

分子量

370.38

CAS No.

649735-46-6

Solubility (25°C)*

体外

DMSO

74 mg/mL (199.79 mM)

Ethanol

5 mg/mL (13.49 mM)

Water

Insoluble

体内（毎回新しく調製した物を用意してください）

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 この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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 この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。	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.

* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明	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.
in vitro	Brivanib (BMS-540215) also inhibits VEGFR1 and FGFR-1 with IC50 of 0.38 μM and 0.148 μM. It is not sensitive to PDGFRβ, EGFR, LCK, PKCα or JAK-3 with IC50 all above 1900 nM. This compound 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, it exhibits low activity to tumor cell lines. ^[1]
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]

プロトコル(参考用のみ)

キナーゼアッセイ	In Vitro Kinase Assays
キナーゼアッセイ	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). This compound is used in the reactions, which 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.
細胞アッセイ	細胞株	VEGF or FGF stimulated HUVECs
	濃度	~ 10 μM
	反応時間	48 hours
	実験の流れ	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 (BMS-540215) 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.
動物実験	動物モデル	H3396 xenografts in athymic mice
	投薬量	60 mg/kg (orally) or 10 mg/kg (intravenously)
	投与方法	Administered via oral or i.v.

参考

https://pubmed.ncbi.nlm.nih.gov/16570908/
https://pubmed.ncbi.nlm.nih.gov/18829493/

カスタマーフィードバック

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

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

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Sensitizing cholangiocarcinoma to chemotherapy by inhibition of the drug-export pump MRP3 [ Biomed Pharmacother, 2024, 180:117533]	PubMed: 39405909
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

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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