Nintedanib (BIBF 1120)
(Synonyms: 尼达尼布,Vargatef) 目录号 : GC11705
Nintedanib (BIBF 1120)是一种可口服的三重酪氨酸激酶抑制剂，能够抑制血管内皮生长因子受体（VEGFR）-1、-2和-3，成纤维细胞生长因子受体（FGFR）-1、-2和-3以及血小板衍生生长因子受体（PDGFR）α和β酪氨酸激酶，对HNE-1、CNE-2和HONE-1的半数抑制浓度（IC50）值分别为4.16±0.04μM、5.62±2.64μM和6.32±1.18μM。
Cas No.:656247-17-5
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');)
Nintedanib (BIBF 1120) is an orally available triple tyrosine kinase inhibitor that can inhibit vascular endothelial growth factor receptor (VEGFR) -1, -2, and -3, fibroblast growth factor receptor (FGFR) -1, -2, and -3, as well as platelet-derived growth factor receptor (PDGFR) α and β tyrosine kinases with an IC50 value of 4.16±0.04μM, 5.62±2.64μM, and 6.32±1.18μM for HNE-1, CNE-2, and HONE-1, respectively[1-3]. Nintedanib is also a potent antagonist of growth factors such as platelet-derived growth factor, vascular endothelial growth factor, and basic fibroblast growth factor[2]. Nintedanib has potent antitumor and antiangiogenic activity[4].
In vitro, after treating Hepatocellular carcinoma (HCC) cells with Nintedanib at different doses (0, 1, 5, 10, 15, 20μM) for 48 hours, Nintedanib significantly induced the accumulation of sub-G1-positive cells and apoptosis, and also significantly induced DNA fragmentation in a dose-dependent manner[5]. Three human nasopharyngeal carcinoma (NPC) cell lines, CNE-2, HNE-1, and HONE-1, were treated with Nintedanib (0-10μM) for 72 hours, which significantly inhibited the growth of these three cell lines in a dose-dependent manner. The IC50 values for the effect of Nintedanib on HNE-1, CNE-2, and HONE-1 were 4.16±0.04μM, 5.62±2.64μM, and 6.32±1.18μM, respectively[3].
In vivo, C57BL/6 male mice with lung fibrosis induced by intratracheal bleomycin or silica particles were treated with Nintedanib (30, 60, or 100mg/kg; gavage) daily, which inhibited platelet-derived growth factor (PDGF) receptor activation, fibroblast proliferation and transformation, and significantly reduced bronchoalveolar lavage (BAL) lymphocytes and neutrophils as well as decreased interleukin-1β, keratinocyte chemoattractant (KC), tissue inhibitor of metalloproteinase-1 (TIMP-1) and lung collagen[6]. After treating nude mice (with human tumor xenografts growing in vivo) with Nintedanib (25-100mg/kg daily p.o.), Nintedanib exerts its effects after 3 days of treatment, reduces vessel density and vessel integrity after 5 days, and induces significant tumor growth inhibition[7].
References:
[1] Antoniu SA. Nintedanib (BIBF 1120) for IPF: a tomorrow therapy?. Multidiscip Respir Med. 2012;7(1):41.
[2] Santos ES, Gomez JE, Raez LE. Targeting angiogenesis from multiple pathways simultaneously: BIBF 1120, an investigational novel triple angiokinase inhibitor. Invest New Drugs. 2012;30(3):1261-1269.
[3] Xue C, Tian Y, Zhang J, et al. Efficacy of BIBF 1120 or BIBF 1120 plus chemotherapy on nasopharyngeal carcinoma in vitro and in vivo. Drug Des Devel Ther. 2016;10:1173-1180.
[4] Kutluk Cenik B, Ostapoff KT, Gerber DE, Brekken RA. BIBF 1120 (nintedanib), a triple angiokinase inhibitor, induces hypoxia but not EMT and blocks progression of preclinical models of lung and pancreatic cancer. Mol Cancer Ther. 2013;12(6):992-1001.
[5] Tai WT, Shiau CW, Li YS, et al. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. J Hepatol. 2014;61(1):89-97.
[6] Wollin L, Maillet I, Quesniaux V, Holweg A, Ryffel B. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014;349(2):209-220.
[7] Hilberg F, Roth GJ, Krssak M, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008;68(12):4774-4782.
Nintedanib (BIBF 1120)是一种可口服的三重酪氨酸激酶抑制剂，能够抑制血管内皮生长因子受体（VEGFR）-1、-2和-3，成纤维细胞生长因子受体（FGFR）-1、-2和-3以及血小板衍生生长因子受体（PDGFR）α和β酪氨酸激酶，对HNE-1、CNE-2和HONE-1的半数抑制浓度（IC50）值分别为4.16±0.04μM、5.62±2.64μM和6.32±1.18μM[1-3]。Nintedanib也是血小板衍生生长因子、血管内皮生长因子和碱性成纤维细胞生长因子等生长因子的强效拮抗剂[2]。Nintedanib具有强大的抗肿瘤和抗血管生成活性[4]。
在体外，用不同剂量（0、1、5、10、15、20μM）的Nintedanib处理肝细胞癌（HCC）细胞48小时后，Nintedanib显著诱导了亚G1期阳性细胞的积累和细胞凋亡，并且以剂量依赖性方式显著诱导了DNA片段化[5]。三种人类鼻咽癌（NPC）细胞系CNE-2、HNE-1和HONE-1用Nintedanib（0-10μM）处理72小时，显著抑制了这三种细胞系的生长，且呈剂量依赖性。Nintedanib对HNE-1、CNE-2和HONE-1的影响的半数抑制浓度（IC50）值分别为4.16±0.04μM、5.62±2.64μM和6.32±1.18μM[3]。
在体内，对经气管内注射博莱霉素或硅尘颗粒诱导肺纤维化的C57BL/6雄性小鼠，每天进行Nintedanib（30、60、100mg/kg，灌胃）处理，抑制了血小板衍生生长因子（PDGF）受体激活、成纤维细胞增殖和转化，并显著减少了支气管肺泡灌洗液（BAL）中的淋巴细胞和中性粒细胞，降低了白介素-1β、角质形成细胞趋化因子（KC）、金属蛋白酶组织抑制因子-1（TIMP-1）和肺胶原蛋白[6]。在裸鼠（体内生长人类肿瘤异种移植瘤）中，用Nintedanib（每天口服25-100mg/kg）处理后，Nintedanib在治疗3天后发挥作用，5天后降低血管密度和血管完整性，并诱导显著的肿瘤生长抑制[7]。
| Cell experiment [1]: | |
Cell lines | Hepatocellular carcinoma (HCC) |
Preparation Method | The antiproliferative effects of Nintedanib treatment were assessed in four human HCC cell lines, with cells exposed to Nintedanib at different doses for 48 hours and cell viability determined by MTT assay. |
Reaction Conditions | 0, 1, 5, 10, 15, 20μM; 48h |
Applications | Nintedanib significantly induced the accumulation of sub-G1-positive cells in HCC cells. The induction of apoptosis by Nintedanib was further confirmed by DNA fragmentation assay. Nintedanib exhibited a significant ratio of induction of DNA fragmentation at clinically relevant concentrations in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | C57BL/6 male mice |
Preparation Method | Lung fibrosis was induced in mice by intratracheal bleomycin or silica particle administration. Nintedanib was administered every day by gavage at 30, 60, or 100mg/kg. |
Dosage form | 30, 60, or 100mg/kg; gavage |
Applications | Nintedanib inhibited platelet-derived growth factor (PDGF) receptor activation, fibroblast proliferation, and fibroblast to myofibroblast transformation. Nintedanib significantly reduced bronchoalveolar lavage (BAL) lymphocytes and neutrophils but not macrophages. Furthermore, interleukin-1β, keratinocyte chemoattractant (KC), tissue inhibitor of metalloproteinase-1 (TIMP-1), and lung collagen were significantly reduced. |
References: | |
| Cas No. | 656247-17-5 | SDF | |
| 别名 | 尼达尼布,Vargatef | ||
| 化学名 | methyl (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate | ||
| Canonical SMILES | CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)NC(=C3C4=C(C=C(C=C4)C(=O)OC)NC3=O)C5=CC=CC=C5 | ||
| 分子式 | C31H33N5O4 | 分子量 | 539.62 |
| 溶解度 | 10mg/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 | 1.8532 mL | 9.2658 mL | 18.5316 mL |
| 5 mM | 0.3706 mL | 1.8532 mL | 3.7063 mL |
| 10 mM | 0.1853 mL | 0.9266 mL | 1.8532 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: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet