別名: BIBF 1120, Intedanib 中文名稱:尼達尼布
Nintedanib尼達尼布是一種有效的三重血管激酶抑制劑,作用于VEGFR1/2/3, FGFR1/2/3和PDGFRα/β,在無細胞試驗中IC50分別為34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM和59 nM/65 nM。Phase 3。
Nintedanib Chemical Structure
CAS: 656247-17-5
細胞系 | 實驗類型 | 給藥濃度 | 孵育時間 | 活性描述 | 文獻信息 |
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PLC5 | Cell Viability Assay | 0-20 μM | 48?h | decreases cell viability dose dependently | 24657398 |
HepG2 | Cell Viability Assay | 0-20 μM | 48?h | decreases cell viability dose dependently | 24657398 |
Hep3B | Cell Viability Assay | 0-20 μM | 48?h | decreases cell viability dose dependently | 24657398 |
A549 | Function Assay | 5?μM | 0-1 h | increases AP-1 activation after 30 min | 25843005 |
A549 | Function Assay | 0.01–5?μM | 72 h | enhances SP-D protein expression in a dose-dependent manner at concentrations of up to 5?μM? | 25843005 |
A549 | Function Assay | 0.01–5?μM | 24 h | induces SFTPD?mRNA expression dose dependently | 25843005 |
Mia-Paca2 | Function Assay | 2/5 μM | 24 h | has a general EMT reversal effect? | 26061747 |
T24 | Function Assay | 2/5 μM | 24 h | has a general EMT reversal effect? | 26061747 |
A549 | Function Assay | 2/5 μM | 24 h | has a general EMT reversal effect? | 26061747 |
SKOV3 | Function Assay | 5 μM | 24 h | induces a significant increase in the promoter activities of E-cad,?CDH1, and?CDH3 | 26061747 |
HuH7 | Cell Viability Assay | 0-20 μM | 48?h | decreases cell viability dose dependently | 24657398 |
SK-Hep1 | Cell Viability Assay | 0-20 μM | 48?h | decreases cell viability dose dependently | 24657398 |
Hep3B | Apoptosis Assay | 0-20 μM | 48?h | induces cell apoptosis dose dependently | 24657398 |
HepG2 | Apoptosis Assay | 0-20 μM | 48?h | induces cell apoptosis dose dependently | 24657398 |
PLC5 | Apoptosis Assay | 0-20 μM | 48?h | induces cell apoptosis dose dependently | 24657398 |
HuH7 | Apoptosis Assay | 0-20 μM | 48?h | induces cell apoptosis dose dependently | 24657398 |
SK-Hep1 | Apoptosis Assay | 0-20 μM | 48?h | induces cell apoptosis dose dependently | 24657398 |
NIH3T3 | Function assay | 50 nM | 1 hr | Inhibition of VEGFR2 transfected in mouse NIH3T3 cells at 50 nM incubated for 1 hr measured after 32 hrs washout followed by VEGF stimulation for 10 mins by Western blotting | 18559524 |
Sf9 | Function assay | 20 mins | Inhibition of mouse GST-fused VEGFR2 expressed in Sf9 insect cells after 20 mins by scintillation counting, IC50 = 0.013 μM. | 18559524 | |
Sf9 | Function assay | 20 mins | Inhibition of human GST-fused VEGFR2 expressed in Sf9 insect cells after 20 mins by scintillation counting, IC50 = 0.021 μM. | 18559524 | |
HT-29 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 4.9 μM. | 28190652 | |
SKOV3 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human SKOV3 cells after 72 hrs by MTT assay, IC50 = 28.76 μM. | 28190652 | |
BL21 (DE3) | Function assay | 30 mins | Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, Ki = 0.0056 μM. | 28351607 | |
BL21 (DE3) | Function assay | 30 mins | Inhibition of His6-tagged MELK catalytic domain (1 to 340 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3) cells using Bcl-GL as substrate measured after 30 mins in presence of [gamma32P]ATP by liquid scintillation counting method, IC50 = 0.043 μM. | 28351607 | |
HT-29 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human HT-29 cells after 72 hrs by MTT assay, IC50 = 0.83 μM. | 28826084 | |
MCF7 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human MCF7 cells after 72 hrs by MTT assay, IC50 = 8.28 μM. | 28826084 | |
A549 | Antiproliferative assay | 72 hrs | Antiproliferative activity against human A549 cells after 72 hrs by MTT assay, IC50 = 22.62 μM. | 28826084 | |
NIH/3T3 | Function assay | 42 hrs | Inhibition of PDGFR in mouse NIH/3T3 cells assessed as reduction in recombinant human PDGF-BB-induced cell proliferation after 42 hrs by cell titer 96 aqueous one solution based assay, IC50 = 0.085 μM. | 29152045 | |
NIH3T3 | Function assay | 1 hr | Inhibition of VEGF-stimulated human VEGFR2 phosphorylation expressed in mouse NIH3T3 cells pretreated for 1 hr measured 32 hrs after drug dose by immunoprecipitation based pulse-chase experiment | 19522465 | |
H1703 | Growth Inhibition Assay | IC50=0.05 μM | 23729403 | ||
Sf9 | Function assay | Inhibition of human VEGFR2 expressed in Sf9 cells, IC50 = 0.005 μM. | 19522465 | ||
BRP | Apoptosis assay | Induction of apoptosis in BRP cells assessed as caspase-3 cleavage | 19522465 | ||
BRP | Antiangiogenic assay | Antiangiogenic activity BRP cells assessed as inhibition of cell proliferation by [3H]thymidine incorporation assay | 19522465 | ||
TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for TC32 cells | 29435139 | ||
A673 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for A673 cells | 29435139 | ||
DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY cells | 29435139 | ||
Saos-2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Saos-2 cells | 29435139 | ||
BT-37 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 cells | 29435139 | ||
SK-N-SH | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SK-N-SH cells | 29435139 | ||
NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB1643 cells | 29435139 | ||
OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for OHS-50 cells | 29435139 | ||
LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for LAN-5 cells | 29435139 | ||
DAOY | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for DAOY cells | 29435139 | ||
Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells | 29435139 | ||
MG 63 (6-TG R) | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for MG 63 (6-TG R) cells | 29435139 | ||
Rh30 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh30 cells | 29435139 | ||
U-2 OS | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for U-2 OS cells | 29435139 | ||
OHS-50 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for OHS-50 cells | 29435139 | ||
Rh41 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh41 cells | 29435139 | ||
SJ-GBM2 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for SJ-GBM2 cells | 29435139 | ||
NB-EBc1 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for NB-EBc1 cells | 29435139 | ||
LAN-5 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells | 29435139 | ||
NB1643 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for NB1643 cells | 29435139 | ||
SK-N-MC | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-MC cells | 29435139 | ||
TC32 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for TC32 cells | 29435139 | ||
Rh18 | qHTS assay | qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for Rh18 cells | 29435139 | ||
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產品描述 | Nintedanib尼達尼布是一種有效的三重血管激酶抑制劑,作用于VEGFR1/2/3, FGFR1/2/3和PDGFRα/β,在無細胞試驗中IC50分別為34 nM/13 nM/13 nM, 69 nM/37 nM/108 nM和59 nM/65 nM。Phase 3。 | |||||||||||
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靶點 |
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體外研究(In Vitro) | ||||
體外研究活性 | BIBF1120對酪氨酸激酶受體如EGFR, HER2, InsR, IGF1R 或者細胞周期激酶 CDK1, CDK2 和CDK4抑制效果不大, IC50都大于1x103nM。BIBF1120強抑制VEGF-刺激的HUVEC 和VEGF-刺激的HSMEC,EC50分別為9 和 7 nM。相反,BIBF1120 作用于FaDu, Calu-6 和Hela時EC50則大到幾百倍。[1] |
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激酶實驗 | 激酶實驗 | |||
VEGFR-2的胞質酪氨酸激酶域克隆到pFastBac載體上,與谷胱甘肽巰基轉移酶 (GST)相融合。 GST融合蛋白在SF-9昆蟲細胞中表達,用重元素萃取分離法提取。HEPEX萃取液包括20 mM HEPES (pH 為7.4), 100 mM NaCl, 10 mM ss-甘油磷酸鹽, 10 mM 聚硝基磷酸單苯酯, 30mM NaF, 5 mM EDTA, 5% 甘油, 1% Triton X-100, 1 mM Na3VO4, 0.1% SDS, 0.5μg/ml 抑肽素A, 2.5 μg/ml 3,4-二氯異香豆素(絲氨酸蛋白酶的不可逆抑制劑), 2.5 μg/ml反式-環(huán)氧琥珀酰-L-亮氨酰-L-氨基丁烷, 20 KIU/ml 抑肽酶, 2 μg/ml 亮抑肽酶, 1 mM苯甲脒,和0.002% PMSF。谷氨酸和酪氨酸按4:1比例隨機組成的聚合物作為基底物,每組50ul的反應液包括5 % DMSO, 40 mM HEPES (pH 為 7.4), 5 mM MgCl2, 5 mM MnCl2, 0.5 mg/ml 聚谷氨酸/酪氨酸, 0.05% Triton X-100, 100 μM ATP, 1 μCi [γ-33P]ATP ,和 10 μl酶制劑。實驗在室溫下進行20分鐘,最后加入10 μl 5 % H3PO4終止反應。沉淀物轉移到GF/B 過濾器中,使用與96孔過濾器相配的萬能采集器收集。通過閃爍計數器測定混合物的放射能。 | ||||
細胞實驗 | 細胞系 | HUVEC, HUASMC,和BRP細胞系 | ||
濃度 | 50 nM | |||
孵育時間 | 2小時 | |||
方法 | 不同的腫瘤細胞系在96孔板上培養(yǎng)24小時。然后加入不同濃度的BIBF1120,處理72小時。通過Alamar-Blue染色的熒光強度測試EC50值。 |
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實驗圖片 | 檢測方法 | 檢測指標 | 實驗圖片 | PMID |
Western blot | p-EGFR / FGFR1 / p-AKT / AKT / p-ERK / ERK Cyclin A / Cyclin D1 / Cyclin E / CDK2 / CDK4 / CDK6 p-SMAD3 / SMAD3 / p-p38 MAPK / p38 MAPK Fibronectin / Collagen 1a1 |
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27581340 | |
Immunofluorescence | Vimentin / E-cadherin |
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29934570 |
體內研究(In Vivo) | ||
體內研究活性 | 在小鼠的Fadu 移植瘤中,按鼠體重,每千克處理100mg BIBF1120,結果顯示腫瘤血管密度降低76%。BIBF1120 作用于移植瘤模型Caki-1, HT-29, SKOV-3, Calu6 和PAC-120同樣有顯著的抑制效果。BIBF1120已用于治療多種癌癥,包括:非小細胞肺癌,前列腺癌,卵巢癌,及結腸直腸癌。且BIBF1120目前處于二期臨床實驗階段。[1] |
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動物實驗 | Animal Models | 雌性無胸腺NMRI-nu/nu鼠 |
Dosages | 100 mg/kg | |
Administration | 口服處理 |
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NCT Number | Recruitment | Conditions | Sponsor/Collaborators | Start Date | Phases |
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NCT06200714 | Recruiting | Idiopathic Pulmonary Fibrosis|Diarrhoea |
Boehringer Ingelheim |
April 30 2024 | -- |
NCT05676112 | Withdrawn | Pulmonary Fibrosis |
Boehringer Ingelheim|China-Japan Friendship Hospital |
December 29 2023 | -- |
NCT06070610 | Completed | Healthy |
Boehringer Ingelheim |
November 8 2023 | Phase 1 |
NCT05755308 | Not yet recruiting | Idiopathic Pulmonary Fibrosis |
Fondazione Policlinico Universitario Agostino Gemelli IRCCS |
October 2023 | Not Applicable |
NCT06071013 | Not yet recruiting | Non-small Cell Lung Cancer|EGFR Gene Mutation|EGFR-TKI Resistant Mutation |
China Medical University Hospital |
September 28 2023 | Phase 1|Phase 2 |
分子量 | 539.62 | 分子式 | C31H33N5O4 |
CAS號 | 656247-17-5 | SDF | Download Nintedanib SDF |
Smiles | CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N=C(C3=CC=CC=C3)C4=C(NC5=C4C=CC(=C5)C(=O)OC)O | ||
儲存條件(自收到貨起) | |||
體外溶解度 |
DMSO : 10 mg/mL ( (18.53 mM) ;DMSO吸濕會降低化合物溶解度,請使用新開封DMSO) Water : Insoluble Ethanol : Insoluble |
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體內溶解配方 現配現用,請按從左到右的順序依次添加,澄清后再加入下一溶劑 |
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第一步:請輸入基本實驗信息(考慮到實驗過程中的損耗,建議多配一只動物的藥量)
第二步:請輸入動物體內配方組成(配方適用于不溶于水的藥物;不同批次藥物配方比例不同,請聯系Selleck為您提供正確的澄清溶液配方)
計算結果:
工作液濃度: mg/ml;
DMSO母液配制方法: mg 藥物溶于μL DMSO溶液(母液濃度mg/mL,注:如該濃度超過該批次藥物DMSO溶解度,請先聯系Selleck);
體內配方配制方法:取μL DMSO母液,加入μL PEG300,混勻澄清后加入μL Tween 80,混勻澄清后加入μL ddH2O,混勻澄清。
體內配方配制方法:取μL DMSO母液,加入μL Corn oil,混勻澄清。
注意:1. 首先保證母液是澄清的;
2.一定要按照順序依次將溶劑加入,進行下一步操作之前必須保證上一步操作得到的是澄清的溶液,可采用渦旋、超聲或水浴加熱等物理方法助溶。
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