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Nintedanib

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Chemical Structure| 656247-17-5 同义名 : BIBF 1120;Intedanib
CAS号 : 656247-17-5
货号 : A181556
分子式 : C31H33N5O4
纯度 : 99+%
分子量 : 539.62
MDL号 : MFCD11974012
存储条件：

粉末 Keep in dark place,Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 10 mg/mL(18.53 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

IP 2% DMSO+water 0.1 mg/mL clear

PO 0.5% CMC-Na 60 mg/mL suspension

生物活性
靶点

  • VEGFR1

    VEGFR1, IC50:34 nM

  • VEGFR3

    VEGFR3, IC50:13 nM

  • VEGFR2

    VEGFR2, IC50:13 nM

  • PDGFRβ

    PDGFRβ, IC50:65 nM
描述 VEGF/VEGFR (vascular endothelial growth factor/vascular endothelial growth factor receptor) pathway plays a key role in tumor angiogenesis by promotion of vascular and lymphatic endothelial, as well as survival, and invasion, thus resulting in neovascularization, tumor growth and metastasis. In addition, blockade of additional proangiogenic receptor tyrosine kinases, including PDGFR and FGFR, may improve long-term clinical outcomes. BIBF 1120 is a multi-RTKs inhibitor with IC50 values of 13nM, 13nM , 16nM , 26nM , 34nM , 37nM , 59nM , 65nM , 69nM , 108nM for VEGFR2, VEGFR3, LCK, FLT3, VEGFR1, FGFR2, PDGFRα, PDGFRβ, FGFR1, FGFR3 (measured by enzymatic assays), less potent to Src, Lyn and FGFR4 with IC50 values of 156nM , 195nM and 610nM, respectively. Treatment with BIBF 1120 resulted in cell proliferation and apoptosis (EC50<10nM) in HUVECs, HSMECs, as well as the downstream p-MAPK and p-AKT (0.1-1μM). Daily oral treatment with BIBF 1120 at dose of 100mg/kg for 5 days reduced vessel density by 76% in FaDu xenografts, as well as markedly reduced both Meca 32–positive and PDGFRβ-positive cells predominantly in the intratumoral compartment. Once daily oral administration of BIBF 1120 at dose of 50mg/kg and 100mg/kg inhibited tumor growth both in a model of human head and neck small cell carcinoma (FaDu cells) and in a human renal cancer model (Caki-1 cells)[1].
作用机制 BIBF 1120 is ATP-competitive proangiogenic receptor tyrosine kinase inhibitor, which can bound in the active site of the VEGFR-2.[1]
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
A549 2/5 μM Function Assay 24 h has a general EMT reversal effect  26061747
A549 0.01–5 μM Function Assay 24 h induces SFTPD mRNA expression dose dependently 25843005
A549 0.01–5 μM Function Assay 72 h enhances SP-D protein expression in a dose-dependent manner at concentrations of up to 5 μM  25843005
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03361319 NSCLC, Recurrent ... 展开 >> Adenocarcinoma of Lung 收起 << Phase 1 Phase 2 Not yet recruiting January 2022 -
NCT02863055 Malignant Pleural Mesothelioma Phase 2 Recruiting October 2020 Belgium ... 展开 >> UZ Antwerpen Recruiting Antwerpen, Belgium Contact: Jan Van Meerbeeck, prof          UZ Gent Recruiting Gent, Belgium Contact: Veerle Surmont, Prof          Italy Ospedale San Paolo Recruiting Milan, Italy Contact: Andrea Luciani, Dr          United Kingdom Manchester University NHS Foundation Trust - UHSM-Wythenshawe Hospital Recruiting Wythenshawe, Manchester, United Kingdom, M23 9LT Principal Investigator: Paul Taylor          Royal Marsden Hospital Recruiting Chelsea, United Kingdom Contact: Sanjay Popat, Dr          Royal Marsden Hospital - Kingston Recruiting Kingston, United Kingdom Contact: Sanjay Popat, Dr          Sheffield Teaching Hospitals NHS Foundation Trust - Weston Park Hospital Recruiting Sheffield, United Kingdom Contact: Robin Young, Dr          NHS South Tyneside-South Tyneside District Hospital Recruiting South Shields, United Kingdom Contact: Rhona McMenemin, Dr          Royal Marsden Hospital Recruiting Sutton, United Kingdom Contact: Sanjay Popat, Dr 收起 <<
NCT02597933 Scleroderma, Systemic Phase 3 Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.85mL

0.37mL

0.19mL

9.27mL

1.85mL

0.93mL

18.53mL

3.71mL

1.85mL
参考文献

[1]Hilberg F, Roth GJ, et al. BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy. Cancer Res. 2008 Jun 15;68(12):4774-82.

[2]Roth GJ, Heckel A, 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). J Med Chem. 2009 Jul 23;52(14):4466-80.

[3]Wollin L, Maillet I, et al. Antifibrotic and anti-inflammatory activity of the tyrosine kinase inhibitor nintedanib in experimental models of lung fibrosis. J Pharmacol Exp Ther. 2014 May;349(2):209-20.

[4]Öztürk Akcora B, Storm G, et al. Tyrosine kinase inhibitor BIBF1120 ameliorates inflammation, angiogenesis and fibrosis in CCl4-induced liver fibrogenesis mouse model. Sci Rep. 2017 Mar 14;7:44545.

[5]Nintedanib