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Tivozanib

別名: AV-951, KRN-951 中文名稱：替沃扎尼

Tivozanib是一種有效的，選擇性VEGFR抑制劑，作用于VEGFR1/2/3時(shí)，IC50分別為0.21 nM/0.16 nM/0.24 nM，也抑制PDGFR和c-Kit，作用于FGFR-1， Flt3， c-Met EGFR和IGF-1R活性較弱。Phase 3。

Tivozanib Chemical Structure

Tivozanib Chemical Structure

CAS: 475108-18-0

規(guī)格 價(jià)格 庫(kù)存 購(gòu)買數(shù)量
10mM (1mL in DMSO) 1963.28 現(xiàn)貨
5mg 977.17 現(xiàn)貨
10mg 1415.05 現(xiàn)貨
50mg 4648.03 現(xiàn)貨
100mg 8165.43 現(xiàn)貨
1g 24488.1 現(xiàn)貨
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Tivozanib相關(guān)產(chǎn)品

相關(guān)信號(hào)通路圖

VEGFR Signaling Pathways

VEGFR信號(hào)通路圖

細(xì)胞實(shí)驗(yàn)數(shù)據(jù)示例

細(xì)胞系 實(shí)驗(yàn)類型 給藥濃度 孵育時(shí)間 活性描述 文獻(xiàn)信息
MCF7 cells Proliferation assay Antiproliferative activity against human MCF7 cells, IC50=0.38 μM 24583357
DAOY qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for DAOY 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
BT-37 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for BT-37 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
U-2 OS qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for U-2 OS 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
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
LAN-5 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for LAN-5 cells 29435139
Rh18 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh18 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
RD qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for RD cells 29435139
Rh41 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Primary screen for Rh41 cells 29435139
A673 qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for A673 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
SK-N-SH qHTS assay qHTS of pediatric cancer cell lines to identify multiple opportunities for drug repurposing: Confirmatory screen for SK-N-SH cells 29435139
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生物活性

產(chǎn)品描述 Tivozanib是一種有效的，選擇性VEGFR抑制劑，作用于VEGFR1/2/3時(shí)，IC50分別為0.21 nM/0.16 nM/0.24 nM，也抑制PDGFR和c-Kit，作用于FGFR-1， Flt3， c-Met EGFR和IGF-1R活性較弱。Phase 3。
靶點(diǎn)
VEGFR2 [1]
(Cell-free assay)		 VEGFR3 [1]
(Cell-free assay)		 EphB2 [1]
(Cell-free assay)		 VEGFR1 [1]
(Cell-free assay)		 PDGFRα [1]
(Cell-free assay)		 點(diǎn)擊更多
6.5 nM 15 nM 24 nM 30 nM 40 nM
體外研究(In Vitro)
體外研究活性 AV-951 也抑制PDGFR?和c-Kit的磷酸化作用，IC50 分別為1.72nm 和1.63nM。AV-951阻斷VEGF依賴的MAPK活性和內(nèi)皮細(xì)胞增殖。[1]AV-951是新型喹啉-尿素派生物。[2]
激酶實(shí)驗(yàn) 激酶實(shí)驗(yàn)
加入1 μmol/L ATP進(jìn)行無(wú)細(xì)胞激酶實(shí)驗(yàn)，分四組進(jìn)行，測(cè)定AV-951作用于重組受體和非受體酪氨酸激酶的IC50值。用于細(xì)胞實(shí)驗(yàn)，細(xì)胞在含0.5% FBS的培養(yǎng)基中饑餓過(guò)夜。加入AV-951或0.1% DMSO，溫育1小時(shí)，然后在37oC下加入同源配體誘導(dǎo)。誘導(dǎo)受體磷酸化持續(xù)5分鐘。加溶解buffer(包含1% NP40, 0.5%脫氧膽酸鈉, 0.1% SDS, 100 μg/mL苯甲磺酰氟, 1 mmol/L Na3VO4,及溶在PBS中的3% 抑肽酶)溶解細(xì)胞。然后加入合適的抗體進(jìn)行免疫沉淀反應(yīng)，及加入磷酸酪氨酸進(jìn)行免疫印跡。分析回歸曲線計(jì)算IC50值。
細(xì)胞實(shí)驗(yàn) 細(xì)胞系 人類臍靜脈內(nèi)皮細(xì)胞(HUVEC) 和正常人類皮膚成纖維細(xì)胞
濃度 1 μM
孵育時(shí)間 15分鐘
方法 癌細(xì)胞接種在96孔板上，在含10% FBS的培養(yǎng)基上培養(yǎng)24小時(shí)。加入AV-951，溫育72小時(shí)。使用WST-1試劑探測(cè)細(xì)胞活力。
體內(nèi)研究(In Vivo)
體內(nèi)研究活性 活體研究顯示AV-951降低移植瘤微血管密度和抑制移植瘤VEGFR-2磷酸化作用水平，尤其當(dāng)AV-951濃度為1mg/kg (口服處理)。在無(wú)胸腺鼠中AV-951幾乎抑制全部的移植瘤生長(zhǎng)，腫瘤生長(zhǎng)抑制率（TGI）>85%。[1]AV-951作用于人類移植瘤模型包括肺, 胸腺, 結(jié)腸, 卵巢, 胰臟和前列腺癌，顯示出抗癌活性。[2]鼠類腹膜彌散腫瘤模型研究顯示AV-951可延長(zhǎng)腫瘤攜帶鼠的壽命。[3]
動(dòng)物實(shí)驗(yàn) Animal Models 無(wú)胸腺鼠(RH-rnu/rnu)
Dosages 1 mg/kg
Administration 口服處理
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04645160 Recruiting
Cholangiocarcinoma|Bile Duct Neoplasm|Biliary Tract Malignancy
National Cancer Institute (NCI)|National Institutes of Health Clinical Center (CC)
 March 4 2022 Phase 1|Phase 2
NCT03136627 Completed
Carcinoma Renal Cell
AVEO Pharmaceuticals Inc.|Bristol-Myers Squibb
 March 22 2017 Phase 1|Phase 2
NCT01853644 Completed
Recurrent Epithelial Ovarian Cancer|Recurrent Fallopian Tube Cancer|Recurrent Primary Peritoneal Cancer
Northwestern University|National Comprehensive Cancer Network
 June 6 2013 Phase 2
NCT01834183 Withdrawn
Renal Cell Carcinoma
Dana-Farber Cancer Institute
 June 2013 Phase 2
NCT01807156 Terminated
Hepatocellular Cancer
Emory University|AVEO Pharmaceuticals Inc.
 March 2013 Phase 2

化學(xué)信息&溶解度

分子量 454.86 分子式

C22H19ClN4O5
CAS號(hào) 475108-18-0 SDF Download Tivozanib SDF
Smiles CC1=CC(=NO1)NC(=O)NC2=C(C=C(C=C2)OC3=C4C=C(C(=CC4=NC=C3)OC)OC)Cl
儲(chǔ)存條件(自收到貨起)

體外溶解度
批次：

DMSO : 20 mg/mL ( (43.96 mM) ；DMSO吸濕會(huì)降低化合物溶解度，請(qǐng)使用新開封DMSO)

Water : Insoluble

Ethanol : Insoluble

摩爾濃度計(jì)算器

體內(nèi)溶解度
批次：

現(xiàn)配現(xiàn)用，請(qǐng)按從左到右的順序依次添加，澄清后再加入下一溶劑

 動(dòng)物體內(nèi)配方計(jì)算器

實(shí)驗(yàn)計(jì)算

摩爾濃度計(jì)算器

質(zhì)量 濃度 體積 分子量

動(dòng)物體內(nèi)配方計(jì)算器（澄清溶液）

第一步：請(qǐng)輸入基本實(shí)驗(yàn)信息（考慮到實(shí)驗(yàn)過(guò)程中的損耗，建議多配一只動(dòng)物的藥量）

mg/kg g μL 只

第二步：請(qǐng)輸入動(dòng)物體內(nèi)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(qǐng)聯(lián)系Selleck為您提供正確的澄清溶液配方）

% DMSO % % Tween 80 % ddH2O
%DMSO %

計(jì)算結(jié)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(guò)該批次藥物DMSO溶解度，請(qǐng)先聯(lián)系Selleck）；

體內(nèi)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(nèi)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(jìn)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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常見(jiàn)問(wèn)題及建議解決方法

問(wèn)題 1:
Would you please provide a little bit more detail regarding how to prepare the Tivozanib for in vivo treatment and the storage condition?

回答：
For in vivo formula, we recommend to use 2% DMSO+30% PEG 300+ddH2O up to 1mg/mL. Once dissolved it in solution, please make small aliquots and store them at -80C up to 6 months without repeated thawing and refreezing.

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