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尼达尼布 /Nintedanib {[allProObj[0].p_purity_real_show]}

货号:A181556 同义名: BIBF 1120;Intedanib

Nintedanib(BIBF 1120)是一种强效的三重血管激酶抑制剂,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、59 nM和65 nM。

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Nintedanib 化学结构 CAS号:656247-17-5
Nintedanib 化学结构
CAS号:656247-17-5
Nintedanib 3D分子结构
CAS号:656247-17-5
Nintedanib 化学结构 CAS号:656247-17-5
Nintedanib 3D分子结构 CAS号:656247-17-5
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Nintedanib 纯度/质量文件 产品仅供科研

货号:A181556 标准纯度: {[allProObj[0].p_purity_real_show]}
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产品名称 PDGFR PDGFRα PDGFRβ 其他靶点 纯度
Tyrphostin A9 +

PDGFR, IC50: 0.5 μM

EGFR 98%
Tyrphostin AG1296 99%+
Motesanib Diphosphate ++

PDGFR, IC50: 84 nM

98%
Pazopanib ++

PDGFR, IC50: 84 nM

99%
Imatinib +

PDGFR, IC50: 100 nM

c-Kit 98%
Imatinib Mesylate +

PDGFR, IC50: 100 nM

c-Kit 99%
Sennoside B 99%+
PP121 ++++

PDGFR, IC50: 2 nM

VEGFR,mTOR 99%+
Crenolanib ++++

PDGFRα, Kd: 2.1 nM

++++

PDGFRβ, Kd: 3.2 nM

99%+
Masitinib +

PDGFRα, IC50: 540 nM

+

PDGFRβ, IC50: 800 nM

99%+
Ki8751 ++

PDGFRα, IC50: 67 nM

c-Kit 98+%
Tivozanib ++

PDGFRα, IC50: 40 nM

++

PDGFRβ, IC50: 49 nM

99%+
Ponatinib ++++

PDGFRα, IC50: 1.1 nM

98%
Amuvatinib ++

PDGFRα (V561D), IC50: 40 nM

99%+
Axitinib +++

PDGFRα, IC50: 5.0 nM

++++

PDGFRβ, IC50: 1.6 nM

98%
CP-673451 +++

PDGFRα, IC50: 10 nM

++++

PDGFRβ, IC50: 1 nM

99%+
Telatinib +++

PDGFRα, IC50: 15 nM

c-Kit 99%+
Nintedanib ++

PDGFRα, IC50: 59 nM

++

PDGFRβ, IC50: 65 nM

99+%
Avapritinib ++++

PDGFRα (D842V), IC50: 0.5 nM

99%+
MK-2461 +++

PDGFRβ, IC50: 22 nM

98%+
Lactate +++

PDGFRβ, IC50: 27 nM

FLT3,c-Kit 85%
Linifanib ++

PDGFRβ, IC50: 66 nM

99%+
AZD2932 +++

PDGFRβ, IC50: 4 nM

c-Kit 98%
Dovitinib +++

PDGFRβ, IC50: 27 nM

FLT3,c-Kit 99%+
Sorafenib ++

mPDGFRβ, IC50: 57 nM

PDGFRβ, IC50: 57 nM

99%
Sunitinib ++++

PDGFRβ , IC50: 2 nM

FLT3 98%
Orantinib +++

PDGFRβ, Ki: 8 nM

99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。
产品名称 FGFR FGFR1 FGFR2 FGFR3 FGFR4 其他靶点 纯度
Tyrphostin AG1296 +

FGFR (Swiss 3T3), IC50: 12.3 μM

PDGFR 99%+
Pazopanib +

FGFR, IC50: 140 nM

99%
Erdafitinib RET 99%+
Gambogenic acid 98+%
Sulfatinib +++

FGFR1, IC50: 15 nM

99+%
Nintedanib esylate +

FGFR1, IC50: 69 nM

++

FGFR2, IC50: 37 nM

+

FGFR3, IC50: 108 nM

98%
Zoligratinib +++

FGFR1, IC50: 9.3 nM

+++

FGFR2, IC50: 7.6 nM

++

FGFR3, IC50: 22 nM

+

FGFR4, IC50: 290 nM

99%+
MK-2461 +

FGFR1, IC50: 65 nM

++

FGFR2, IC50: 39 nM

++

FGFR3, IC50: 50 nM

98%+
SU 5402 ++

FGFR1, IC50: 30 nM

98%
Brivanib +

FGFR1, IC50: 148 nM

99%+
Lucitanib ++

FGFR1, IC50: 17.5 nM

+

FGFR2, IC50: 82.5 nM

99%+
Ponatinib ++++

FGFR1, IC50: 2.2 nM

98%
PD-166866 +

FGFR1, IC50: 52.4 nM

98%
Narazaciclib ++

FGFR1, IC50: 26 nM

RET 99%+
Lactate +++

FGFR1, IC50: 8 nM

+++

FGFR3, IC50: 9 nM

FLT3,c-Kit 85%
Lenvatinib mesylate ++

FGFR1, IC50: 46 nM

c-RET 99%
LY2874455 ++++

FGFR1, IC50: 2.8 nM

++++

FGFR2, IC50: 2.6 nM

+++

FGFR3, IC50: 6.4 nM

+++

FGFR4, IC50: 6 nM

99%+
FIIN-2 +++

FGFR1, IC50: 3.09 nM

+++

FGFR2, IC50: 4.3 nM

++

FGFR3, IC50: 27 nM

++

FGFR4, IC50: 45.3 nM

98%
FIIN-3 +++

FGFR1, IC50: 13.1 nM

++

FGFR2, IC50: 21 nM

++

FGFR3, IC50: 31.4 nM

++

FGFR4, IC50: 35.3 nM

98%
Infigratinib ++++

FGFR1, IC50: 0.9 nM

++++

FGFR2, IC50: 1.4 nM

++++

FGFR3 (K650E), IC50: 4.9 nM

FGFR3, IC50: 1.0 nM

+

FGFR4, IC50: 60 nM

99%+
Danusertib ++

FGFR1, IC50: 47 nM

RET 99%+
R1530 ++

FGFR1, IC50: 28 nM

98%
ENMD-2076 +

FGFR1, IC50: 92.7 nM

+

FGFR2, IC50: 70.8 nM

FLT3,RET 98%
Dovitinib +++

FGFR1, IC50: 8 nM

+++

FGFR3, IC50: 9 nM

FLT3,c-Kit 99%+
Sorafenib +

FGFR1, IC50: 580 nM

99%
SSR128129E +

FGFR1, IC50: 1.9 μM

99%+
AZD-4547 ++++

FGFR1, IC50: 0.2 nM

++++

FGFR2, IC50: 2.5 nM

++++

FGFR3, IC50: 1.8 nM

98%
Lenvatinib ++

FGFR1, IC50: 46 nM

RET 98%
PD173074 ++

FGFR1, IC50: ~25 nM

99%+
S49076 ++

FGFR1, IC50: 18 nM

+++

FGFR2, IC50: 17 nM

+++

FGFR3, IC50: 15 nM

98%
Futibatinib ++++

FGFR1, IC50: 1.8 nM

++++

FGFR2, IC50: 1.4 nM

++++

FGFR3, IC50: 1.6 nM

+++

FGFR4, IC50: 3.7 nM

99%+
Ferulic Acid +

FGFR1, IC50: 3.78 μM

+

FGFR2, IC50: 12.5 μM

98%
Nintedanib +

FGFR1, IC50: 69 nM

++

FGFR2, IC50: 37 nM

+

FGFR3, IC50: 108 nM

+

FGFR4, IC50: 610 nM

99+%
ASP5878 ++++

FGFR1, IC50: 0.47 nM

++++

FGFR2, IC50: 0.6 nM

++++

FGFR3, IC50: 0.74 nM

+++

FGFR4, IC50: 3.5 nM

98%
PRN1371 ++++

FGFR1, IC50: 0.6 nM

++++

FGFR2, IC50: 1.3 nM

+++

FGFR3, IC50: 4.1 nM

++

FGFR4, IC50: 19.3 nM

99%
Derazantinib +++

FGFR1, IC50: 4.5 nM

++++

FGFR2, IC50: 1.8 nM

+++

FGFR3, IC50: 4.5 nM

++

FGFR4, IC50: 34 nM

RET 99%+
ODM-203 +++

FGFR1, IC50: 11 nM

+++

FGFR2, IC50: 16 nM

+++

FGFR3, IC50: 6 nM

++

FGFR4, IC50: 35 nM

99%+
Pemigatinib ++++

FGFR1, IC50: 0.4 nM

++++

FGFR2, IC50: 0.5 nM

++++

FGFR3, IC50: 1.2 nM

++

FGFR4, IC50: 30 nM

99%+
SKLB 610 PDGFR 99%+
Alofanib 99%+
Lirafugratinib 98%
Masitinib mesylate FAK 99%+
BLU9931 +

FGFR3, IC50: 150 nM

+++

FGFR4, IC50: 3 nM

99%+
BO-264 99%+
Fisogatinib +++

FGFR4, IC50: 5 nM

99%+
H3B-6527 ++++

FGFR4, IC50: <1.2 nM

99%+
Roblitinib ++++

FGFR4, IC50: 1.9 nM

99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。
产品名称 VEGFR1 VEGFR2 VEGFR3 其他靶点 纯度
Motesanib Diphosphate ++++

VEGFR1, IC50: 2 nM

++++

VEGFR2, IC50: 3 nM

VEGFR2/Flk1, IC50: 3 nM

+++

VEGFR3, IC50: 6 nM

PDGFR,RET 98%
Tivozanib ++

VEGFR1, IC50: 30 nM

+++

VEGFR2, IC50: 6.5 nM

++

VEGFR3, IC50: 15 nM

99%+
Brivanib +

VEGFR1, IC50: 380 nM

++

VEGFR2, IC50: 25 nM

Flk1, IC50: 25 nM

99%+
Regorafenib +++

VEGFR1, IC50: 13 nM

+++

VEGFR2, IC50: 4.2 nM

+

VEGFR3, IC50: 46 nM

RET 98%
Pazopanib +++

VEGFR1, IC50: 10 nM

++

VEGFR2, IC50: 30 nM

+

VEGFR3, IC50: 47 nM

FGFR,PDGFR,c-Kit 99%
Sitravatinib +++

VEGFR1 (FLT1), IC50: 6 nM

+++

VEGFR2 (KDR), IC50: 5 nM

++++

VEGFR3 (FLT4), IC50: 2 nM

99%+
Foretinib +++

VEGFR1/FLT1, IC50: 6.8 nM

++++

KDR, IC50: 0.86 nM

++++

VEGFR3/FLT4, IC50: 2.8 nM

Tie-2 99%+
MGCD-265 analog ++++

VEGFR1, IC50: 3 nM

++++

VEGFR2, IC50: 3 nM

++++

VEGFR3, IC50: 4 nM

Tie-2 99%+
Lactate +++

VEGFR1/FLT1, IC50: 10 nM

+++

VEGFR2/Flk1, IC50: 13 nM

+++

VEGFR3/FLT4, IC50: 8 nM

FLT3,c-Kit 85%
AEE788 +

FLT1, IC50: 59 nM

+

KDR, IC50: 77 nM

EGFR 98+%
Linifanib ++++

VEGFR1/FLT1, IC50: 3 nM

++++

VEGFR2/KDR, IC50: 4 nM

+

VEGFR3/FLT4, IC50: 190 nM

FLT3 99%+
Vatalanib 2HCl +

VEGFR1/FLT1, IC50: 77 nM

++

VEGFR2/KDR, IC50: 37 nM

VEGFR2/Flk1, IC50: 270 nM

+

VEGFR3/FLT4, IC50: 660 nM

c-Kit,c-Fms 99%+
Axitinib ++++

VEGFR1/FLT1, IC50: 0.1 nM

++++

VEGFR2/KDR, IC50: 0.2 nM

VEGFR2/Flk1, IC50: 0.18 nM

98%
Dovitinib +++

VEGFR1/FLT1, IC50: 10 nM

+++

VEGFR2/Flk1, IC50: 13 nM

+++

VEGFR3/FLT4, IC50: 8 nM

FLT3,c-Kit 99%+
ZM 306416 +

VEGFR1, IC50: 0.33 μM

Src 99%+
KRN-633 +

VEGFR1, IC50: 170 nM

+

VEGFR2, IC50: 160 nM

+

VEGFR3, IC50: 125 nM

c-Kit,BTK 98%
OSI-930 +++

FLT1, IC50: 8 nM

+++

KDR, IC50: 9 nM

99%+
Lenvatinib ++

VEGFR1/FLT1, IC50: 22 nM

++++

VEGFR2/KDR, IC50: 4.0 nM

+++

VEGFR3/FLT4, IC50: 5.2 nM

98%
NVP-BAW2881 +

hVEGFR1, IC50: 820 nM

+++

mVEGF2, IC50: 165 nM

hVEGFR2, IC50: 9 nM

+

hVEGFR3, IC50: 420 nM

98%
Cediranib +++

VEGFR1/FLT1, IC50: 5 nM

++++

VEGFR2/KDR, IC50: 0.5 nM

c-Kit 99%+
Nintedanib ++

VEGFR1, IC50: 34 nM

+++

VEGFR2, IC50: 13 nM

+++

VEGFR3, IC50: 13 nM

FLT3 99+%
BMS-794833 ++

VEGFR2, IC50: 15 nM

99%+
SKLB1002 ++

VEGFR2, IC50: 32 nM

98%
Cabozantinib S-malate ++++

VEGFR2/KDR, IC50: 0.035 nM

99+%
Ki8751 ++++

VEGFR2, IC50: 0.9 nM

c-Kit 98+%
SU 5402 ++

VEGFR2, IC50: 20 nM

98%
Rivoceranib Mesylate ++++

VEGFR2, IC50: 1 nM

RET 98+%
Ponatinib ++++

VEGFR2, IC50: 1.5 nM

98%
LY2874455 +++

VEGFR2, IC50: 7 nM

99%+
ZM323881 HCl ++++

VEGFR2, IC50: <2 nM

98%
AZD2932 +++

VEGFR-2, IC50: 8 nM

c-Kit 98%
Cabozantinib ++++

VEGFR2/KDR, IC50: 0.035 nM

98%
Sorafenib ++

VEGFR2, IC50: 90 nM

VEGFR2/Flk1, IC50: 90 nM

99%
CYC-116 ++

VEGFR2, Ki: 44 nM

FLT3 99%+
Golvatinib ++

VEGFR2, IC50: 16 nM

99%+
Sunitinib +

VEGFR2 , IC50: 80 nM

FLT3 98%
RAF265 ++

VEGFR2, EC50: 30 nM

99%+
PD173074 99%+
BFH772 ++++

VEGFR2, IC50: 3 nM

98%
Semaxinib +

VEGFR2/Flk1, IC50: 1.23 μM

98%
Vandetanib ++

VEGFR2, IC50: 40 nM

+

VEGFR3, IC50: 110 nM

EGFR 98%
SAR131675 ++

VEGFR3, IC50: 23 nM

99%+
ENMD-2076 +

VEGFR2/KDR, IC50: 58.2 nM

++

VEGFR3/FLT4, IC50: 15.9 nM

FLT3,RET 98%
Telatinib +++

VEGFR2, IC50: 6 nM

++++

VEGFR3, IC50: 4 nM

c-Kit 99%+
1. 鼠标悬停在“+”上可以显示相关IC50的具体数值。"+"越多,抑制作用越强。2. "✔"表示该化合物对相应的亚型有抑制作用,但抑制强度暂时没有相关数据。

Nintedanib 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]

Nintedanib 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
A549 5 μM Function Assay 0-1 h increases AP-1 activation after 30 min 25843005

Nintedanib 动物研究

Dose Mice: 50 mg/kg[2] (p.o.), 3 mg/kg - 100 mg/kg[3] (p.o.); 5 mg/kg[4] (i.p.)
Rat: 25 mg/kg - 100 mg/kg[1] (p.o.)
Administration p.o., i.p.
Pharmacokinetics
Animal Mice[5] Rats[5] Monkeys[5]
Dose 50 mg/kg 50 mg/kg (p.o.)
2 mg/kg (i.v.)
40 mg/kg (p.o., cynomolgus monkey)
5 mg/kg (i.v., cynomolgus monkey)
Administration p.o. p.o.
i.v.
p.o.
i.v.
MRT 5.19 h 3.25 h (i.v.) 3.82 h (i.v.)
F 11.9% (p.o.) 13.2% (p.o.)
T1/2 5.15 h 3.95 h (i.v.) 5.95 h (i.v.)
AUC 2720 ng·h/ml 375 ng·h/ml (p.o.)
181 ng·h/ml (i.v.)
2390 ng·h/ml (p.o.)
2260 ng·h/ml (i.v.)
CL 202 ml/min/kg (i.v.) 37.5 ml/min/kg (i.v.)
Cmax 547 ng/ml 105 ng/ml (p.o.)
124 ng/ml (i.v.)
175 ng/ml (p.o.)
1300 ng/ml (i.v.)
Protein bound (%) 92.9% (p.o.)
Protein binding (free drug %) 0.972 98.5% (p.o.)
Vss 41.2 L/kg (i.v.) 8.64 L/kg (i.v.)

Nintedanib 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 - -

Nintedanib 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

Nintedanib 实验方案

计算器
存储液制备 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

Nintedanib 技术信息

CAS号656247-17-5
分子式C31H33N5O4
分子量 539.62
别名 BIBF 1120;Intedanib
运输蓝冰
存储条件

液体 -20°C:3-6个月-80°C:12个月

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

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

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