Nintedanib (BIBF 1120)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
Nintedanib (BIBF 1120)是一种吲哚啉酮衍生的具口服活性的三重激酶抑制剂，对血管内皮生长因子受体（VEGFR1/2/3）、成纤维细胞生长因子受体（FGFR1/2/3 ）和血小板衍生生长因子受体（PDGFRα/β）具有抑制作用，在纳摩尔（IC50, 20-100 nmol/L）范围时通过阻断这些受体介导的信号途径，具有有效的抗血管生成活性[1，2]。
Nintedanib (BIBF 1120)可用于特发性肺纤维化治疗的临床研究，因为这些受体可能参与肺纤维素化的发病机制[3，4]。作为一种新型的血管生成抑制剂，Nintedanib也在各种癌症模型中被广泛评估，其通过抑制肿瘤血管形成，发挥显著的抗肿瘤活性[5-7]。
为进一步评估其在多个肿瘤中的抗肿瘤作用，目前Nintedanib已经进入很多癌症的临床试验中,包括非小细胞肺癌、卵巢癌、结直肠癌、肝癌和许多其他恶性实体瘤。此外，也进行了Nintedanib与其它治疗的联合用药疗法试验，比如在不同肿瘤模型中测试Nintedanib与docetaxel和afatinib联合用药，最常见的药物相关不良反应有腹泻、恶心、呕吐和嗜睡[7]。
参考文献：
[1] Hilberg, F. et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer research 68, 4774-4782, doi:10.1158/0008-5472.CAN-07-6307 (2008).
[2] Roth, G. J. et al. Design, synthesis, and evaluation of indolinones as triple angiokinase inhibitors and the discovery of a highly specific 6-methoxycarbonyl-substituted indolinone (BIBF 1120). Journal of medicinal chemistry 52, 4466-4480, doi:10.1021/jm900431g (2009).
[3] 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. The Journal of pharmacology and experimental therapeutics 349, 209-220, doi:10.1124/jpet.113.208223 (2014).
[4] Antoniu, S. A. Nintedanib (BIBF 1120) for IPF: a tomorrow therapy Multidisciplinary respiratory medicine 7, 41, doi:10.1186/2049-6958-7-41 (2012).
[5] Santos, E. S., Gomez, J. E. & Raez, L. E. Targeting angiogenesis from multiple pathways simultaneously: BIBF 1120, an investigational novel triple angiokinase inhibitor. Investigational new drugs 30, 1261-1269, doi:10.1007/s10637-011-9644-2 (2012).
[6] Wei, X. W., Zhang, Z. R. & Wei, Y. Q. Anti-angiogenic drugs currently in Phase II clinical trials for gynecological cancer treatment. Expert opinion on investigational drugs 22, 1181-1192, doi:10.1517/13543784.2013.812071 (2013).
[7] Mross, K. et al. Phase I study of the angiogenesis inhibitor BIBF 1120 in patients with advanced solid tumors. Clinical cancer research : an official journal of the American Association for Cancer Research 16, 311-319, doi:10.1158/1078-0432.CCR-09-0694 (2010).
[8] Rolfo, C. et al. BIBF 1120/ nintedanib : a new triple angiokinase inhibitor-directed therapy in patients with non-small cell lung cancer. Expert opinion on investigational drugs 22, 1081-1088, doi:10.1517/13543784.2013.812630 (2013).
[9] Tai, W. T. et al. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. Journal of hepatology, doi:10.1016/j.jhep.2014.03.017 (2014).
[10] Reck, M. et al. Docetaxel plus nintedanib versus docetaxel plus placebo in patients with previously treated non-small-cell lung cancer (LUME-Lung 1): a phase 3, double-blind, randomised controlled trial. The lancet oncology 15, 143-155, doi:10.1016/S1470-2045(13)70586-2 (2014).
[11] Bouche, O. et al. Phase II trial of weekly alternating sequential BIBF 1120 and afatinib for advanced colorectal cancer. Anticancer research 31, 2271-2281 (2011).
- 1. da Silva RF, Banzato TP, et al. "Antiangiogenic therapy with Nintedanib affects hypoxia, angiogenesis and apoptosis in the ventral prostate of TRAMP animals." Cell Tissue Res. 2019 Aug 31. PMID:31473819
- 2. Mateus PAM, Kido LA, et al. "Association of anti-inflammatory and antiangiogenic therapies negatively influences prostate cancer progression in TRAMP mice." Prostate. 2018 Dec 25. PMID:30585351
- 3. Pangrazi EN, da Silva RF, et al. "Nintedanib treatment delays prostate dorsolateral lobe cancer progression in the TRAMP model: Contribution to the epithelial-stromal interaction balance." Cell Biol Int. 2017 Oct 5. PMID:28980742
- 4. Janelle DeJong."Determination of Anti-Fibrotic Effects of Possible Scar-Collagen Antagonists on TGF-β1 Treated Dermal Fibroblasts." 2017 Feb 1;7(2):203-217. eCollection 2017.
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 539.62 |
| Cas No. | 656247-17-5 |
| Formula | C31H33N5O4 |
| Synonyms | Vargatef |
| Solubility | insoluble in H2O; insoluble in EtOH; ≥5.34 mg/mL in DMSO |
| Chemical Name | methyl (3Z)-3-[[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]anilino]-phenylmethylidene]-2-oxo-1H-indole-6-carboxylate |
| SDF | Download SDF |
| 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 |
| 运输条件 | 蓝冰运输或根据您的需求运输。 |
| 一般建议 | 不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。溶液形式一般不宜长期储存，请尽快用完。 |
| 细胞实验: [1] | |
|
细胞系 |
PLC5、Hep3B、SK-Hep1、HuH7和HepG2细胞 |
|
制备方法 |
该化合物在DMSO中的溶解度大于10 mM，若配制更高浓度的溶液，一般步骤如下：请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。 |
|
反应条件 |
20 μM，48 hours |
|
实验结果 |
Nintedanib处理48小时后通过MTT实验测定细胞活力。在所有测试的HCC细胞中，Nintedanib显著诱导亚G1阳性细胞的积累。此外，通过对DNA片段化的测定也证明了nintedanib诱导凋亡。在五种HCC细胞系中，在临床相关浓度下，Nintedanib以剂量依赖性方式显著诱导DNA片段化的比例。 |
| 动物实验: [2] | |
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动物模型 |
注射A459、Calu-6或H1993细胞的雌性NOD/SCID小鼠 |
|
给药剂量 |
口服给药，50 mg/kg，每周5天 |
|
实验结果 |
在A549异种移植物中，单一药剂的BIBF 1120有效地减少原发性肿瘤大小。在三种异种移植物中，所有模型中特别是在组合给药组中观察到肿瘤生长速率的降低，其中生长曲线逐渐变为线性。在所有模型中，与对照相比，BIBF 1120和组合给药组中的最终肿瘤体积和重量较低。在A549和H1993异种移植物中，组合给药比单一药剂治疗更有效；然而，在Calu-6异种移植物中，组合治疗与BIBF 1120单一药剂治疗没有明显区别。 |
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注意事项 |
请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同，但仍处于实验系统误差的允许范围内。 |
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References: [1] Tai W T, Shiau C W, Li Y S, et al. Nintedanib (BIBF-1120) inhibits hepatocellular carcinoma growth independent of angiokinase activity. Journal of hepatology, 2014. [2] Cenik B K, Ostapoff K T, Gerber D E, et al. BIBF 1120 (nintedanib), a triple angiokinase inhibitor, induces hypoxia but not EMT and blocks progression of preclinical models of lung and pancreatic cancer. Molecular cancer therapeutics, 2013, 12(6): 992-1001. |
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| Description | BIBF 1120是一种有效的三重激酶抑制剂，对VEGFR1/2/3、FGFR1/2/3 和 PDGFRα/β的IC50值分别为34 nM/13 nM/13 nM、69 nM/37 nM/108 nM和59 nM/65 nM。 | |||||
| 靶点 | VEGFR1/2/3 | FGFR1/2/3 | PDGFRα/β | |||
| IC50 | 34 nM/13 nM/13 nM | 69 nM/37 nM/108 nM | 59 nM/65 nM | |||
质量控制和MSDS
- 批次:
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