Brivanib (BMS-540215)是一种口服有效的ATP竞争性VEGFR-2抑制剂，IC50为25nM，Ki为26nM。
Cas No.:649735-46-6
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
Brivanib (BMS-540215) is an orally active ATP-competitive inhibitor of VEGFR-2, with an IC50 of 25nM and Ki of 26nM [1]. Brivanib can inhibit the phosphorylation of FGFR1 and VEGFR2, and suppress the formation of choroidal neovascularization (CNV)[2]. Brivanib has been widely used to inhibit tumor progression in animal models and to prevent tumor angiogenesis[3].
In vitro, Brivanib treatment for 24 hours significantly inhibited the proliferation of Huh-7 cells, with an IC50 value of 8.6μM[4]. Treatment with 10μM Brivanib for 96 hours significantly inhibited dengue virus (DENV) infection of BHK-21 cells, reversed the decrease in AMPK phosphorylation levels caused by DENV infection, and improved the cellular lipid environment[5].
In vivo, Brivanib treatment via oral administration at a dose of 25mg/kg/day for 7 days significantly inhibited liver fibrosis induced by bile duct ligation (BDL) in mice and reduced the expression of collagen Iα1 mRNA[6]. Oral administration of 90mg/kg of Brivanib daily for 9 days significantly inhibited tumor growth in the L2987 xenograft mouse model[7].
References:
[1] Bhide R S, Cai Z W, Zhang Y Z, et al. Discovery and preclinical studies of (R)-1-(4-(4-Fluoro-2-methyl-1 H-indol-5-yloxy)-5-methylpyrrolo [2, 1-f][1, 2, 4] triazin-6-yloxy) propan-2-ol (BMS-540215), an in vivo active potent VEGFR-2 inhibitor[J]. Journal of medicinal chemistry, 2006, 49(7): 2143-2146.
[2] Li L, Zhu M, Wu W, et al. Brivanib, a multitargeted small‐molecule tyrosine kinase inhibitor, suppresses laser‐induced CNV in a mouse model of neovascular AMD[J]. Journal of Cellular Physiology, 2020, 235(2): 1259-1273.
[3] Allen E, Walters I B, Hanahan D. Brivanib, a dual FGF/VEGF inhibitor, is active both first and second line against mouse pancreatic neuroendocrine tumors developing adaptive/evasive resistance to VEGF inhibition[J]. Clinical Cancer Research, 2011, 17(16): 5299-5310.
[4] Kim H, Lim H Y. Novel EGFR-TK inhibitor EKB-569 inhibits hepatocellular carcinoma cell proliferation by AKT and MAPK pathways[J]. Journal of Korean Medical Science, 2011, 26(12): 1563.
[5] Wan Y, Wu W, Wan Y, et al. Brivanib alaninate inhibited dengue virus proliferation through VEGFR2/AMPK pathway[J]. Pharmacological Research, 2021, 170: 105721.
[6] Nakamura I, Zakharia K, Banini B A, et al. Brivanib attenuates hepatic fibrosis in vivo and stellate cell activation in vitro by inhibition of FGF, VEGF and PDGF signaling[J]. PloS one, 2014, 9(4): e92273.
[7] Marathe P H, Kamath A V, Zhang Y, et al. Preclinical pharmacokinetics and in vitro metabolism of brivanib (BMS-540215), a potent VEGFR2 inhibitor and its alanine ester prodrug brivanib alaninate[J]. Cancer chemotherapy and pharmacology, 2009, 65(1): 55-66.
Brivanib (BMS-540215)是一种口服有效的ATP竞争性VEGFR-2抑制剂，IC50为25nM，Ki为26nM[1]。Brivanib可抑制FGFR1和VEGFR2的磷酸化，并抑制脉络膜新生血管(CNV)的形成[2]。Brivanib已被广泛用于抑制动物模型中的肿瘤进展和预防肿瘤血管生成[3]。
在体外，Brivanib处理24小时显著抑制了Huh-7细胞的增殖，IC50值为8.6μM[4]。使用10μM的Brivanib处理BHK-21细胞96小时，显著抑制了登革热病毒(DENV)对细胞的感染，逆转了DENV感染引起的AMPK磷酸化水平下降，并改善了细胞脂质环境[6]。
在体内，每日口服25mg/kg剂量的Brivanib，连续7天，显著抑制了胆管结扎(BDL)诱导的小鼠肝纤维化，并降低了胶原蛋白Iα1 mRNA的表达[6]。每日口服90mg/kg剂量的Brivanib，连续9天，显著抑制了L2987异种移植小鼠模型中的肿瘤生长[7]。
| Cell experiment [1]: | |
Cell lines | Huh-7 cells |
Preparation Method | Huh-7 cells were cultured in RPMI-1640 medium supplemented with 10% heat-inactivated fetal bovine serum, 100U/ml penicillin, 100μg/ml streptomycin in a humidified incubator at 37°C and 5% CO2. Huh-7 cells were plated at a density of 4×103 cells/ml in a 96-well plate with growth medium for 24h, and then were incubated with the different concentrations of Brivanib (0.01, 0.1, 1, 5, and 10μM) for 24h, the cell viability was analyzed. |
Reaction Conditions | 0.01, 0.1, 1, 5, and 10μM; 24h |
Applications | Brivanib treatment significantly inhibited cell viability of Huh-7 cells in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6 mice |
Preparation Method | C57BL/6 mice were housed in an air-conditioned room with a 12h light/dark cycle and received standard laboratory rat chow and tap water. Cohorts of mice 6-8 weeks old were subjected to BDL performed. Beginning 7 days after BDL, placebo or Brivanib (50mg/kg) was administered daily by the oral route for 7 days. Mice were sacrificed 14 days after BDL and Liver tissue was frozen in liquid nitrogen for analysis. |
Dosage form | 50mg/kg/day; p.o. |
Applications | Brivanib treatment inhibited liver fibrosis induced by BDL in mice. |
References: | |
| Cas No. | 649735-46-6 | SDF | |
| 别名 | 布立尼布; BMS-540215 | ||
| 化学名 | (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-ol | ||
| Canonical SMILES | CC1=CC2=C(N1)C=CC(=C2F)OC3=NC=NN4C3=C(C(=C4)OCC(C)O)C | ||
| 分子式 | C19H19FN4O3 | 分子量 | 370.38 |
| 溶解度 | ≥ 18.5mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.6999 mL | 13.4996 mL | 26.9993 mL |
| 5 mM | 540 μL | 2.6999 mL | 5.3999 mL |
| 10 mM | 270 μL | 1.35 mL | 2.6999 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet