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は、VEGFR2に対するATP競合阻害剤であり、IC50は25 nMです。VEGFR-1およびFGFR-1に対しては中程度の効力がありますが、PDGFR-βに対しては240倍以上の効力があります。フェーズ3。
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.
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. 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.

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). 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.
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 seeded in 96 well plates at a density of 2 × 10³ and incubated for 24 hours, then stimulated by VEGF or FGF at a concentration of 8 or 80 ng/mL. Brivanib (BMS-540215) at various dilutions is added to the cells for another 48 hours. After that, 0.5 μCi of [³H] thymidine is added for 24 hours, and 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
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
Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer [Nadauld LD, et al. Genome Biol, 2014, 15(8):428]	PubMed: 25315765
Inhibition of NRF2 by PIK-75 augments sensitivity of pancreatic cancer cells to gemcitabine. [Duong HQ, et al. Int J Oncol, 2014, 44(3):959-69]	PubMed: 24366069

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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