Cabozantinib (BMS-907351)

For research use only. Not for use in humans.

目录号:S1119 别名: XL184 中文名称:卡博替尼

Cabozantinib (BMS-907351) Chemical Structure

CAS No. 849217-68-1

Cabozantinib (XL184, BMS-907351)是一种有效的VEGFR2抑制剂,在无细胞试验中IC50为0.035 nM,也能有效抑制c-Met、 Ret、 Kit、Flt-1/3/4、Tie2和AXL,IC50分别为1.3 nM,4 nM,4.6 nM,12 nM/11.3 nM/6 nM,14.3 nM 和 7 nM。Cabozantinib 在结肠癌细胞中可通过AKT/GSK-3β/NF-κB信号通路诱导PUMA依赖的凋亡。

规格 价格 库存 购买数量  
10mM (1mL in DMSO) RMB 1800.41 现货
RMB 902.82 现货
RMB 1393.37 现货
RMB 3837.48 现货
RMB 8176.22 现货
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客户使用Selleck生产的Cabozantinib (BMS-907351)发表文献83篇:

产品安全说明书

VEGFR抑制剂选择性比较

生物活性

产品描述 Cabozantinib (XL184, BMS-907351)是一种有效的VEGFR2抑制剂,在无细胞试验中IC50为0.035 nM,也能有效抑制c-Met、 Ret、 Kit、Flt-1/3/4、Tie2和AXL,IC50分别为1.3 nM,4 nM,4.6 nM,12 nM/11.3 nM/6 nM,14.3 nM 和 7 nM。Cabozantinib 在结肠癌细胞中可通过AKT/GSK-3β/NF-κB信号通路诱导PUMA依赖的凋亡。
靶点
VEGFR2/KDR [1]
(Cell-free assay)
c-Met [1]
(Cell-free assay)
Axl [1]
(Cell-free assay)
0.035 nM 1.3 nM 7 nM
体外研究

XL184是多种受体酪氨酸激酶小分子抑制剂,尤其抑制c-Met 和VEGFR2。XL-184也有效作用于Ret, Kit, FLT1, FLT3, FLT4, Tie2, 和 AXL , IC50分别为 4 nM, 4.6 nM, 12 nM, 11.3 nM, 6 nM, 14.3 nM, 和7 nM。XL184微弱抑制 RON 和PDGFR-β,IC50分别为 124 nM和 234 nM,而对FGFR1则几乎没有抑制活性,IC50 为5.294 μM。[1] XL184低浓度(0.1-0.5 μM) 时处理MPNST细胞,也显著抑制组成型和诱导型Met磷酸化及其下游信号,且抑制 HGF诱导的MPNST细胞迁移和侵袭。XL184作用于细胞因子刺激的人脐静脉内皮细胞(HUVECs),也显著抑制Met和VEGFR2磷酸化。虽然XL184浓度为0.1 μM时不能抑制MPNST细胞生长,但是浓度为5-10 μM 时则能显著抑制MPNST细胞生长。[2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
E98NT  NITL[|lIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NGjXN|QxNjBzLUGwJO69VQ>? NYnmcHBKTE2VTx?= MonoTWM2OD16OTDuUS=> MVq8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzR6NECwOkc,OjN2OESwNFY9N2F-
SNU-5  MXrHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NVPsOIIzUUN3ME2gNVkhdk1? NFfZO5c9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{MUmyOlE6OSd-MkG5NlYyQTF:L3G+
Hs746T  M{XxbGdzd3e2aDDJcohq[mm2aX;uJGF{e2G7 NVfZeYNWUUN3ME25Mlkhdk1? NX[5V|Q6RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5NlYyQTFpPkKxPVI3OTlzPD;hQi=>
SNU-1  NX7FcpF3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MUHJR|UxRTV{MkOgcm0> MkDaQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjF7Mk[xPVEoRjJzOUK2NVkyRC:jPh?=
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H441  NUDPN2U3T3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NWr6dmtLUUN3ME2yNVcxOCCwTR?= M2K1[VxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzOUK2NVkyLz5{MUmyOlE6OTxxYU6=
H69 MYPHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? MmfCTWM2OD1{MEKwNEBvVQ>? NVjURoVvRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkG5NlYyQTFpPkKxPVI3OTlzPD;hQi=>
PC3 NXTSU2pZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlfZTWM2OD1zMEiwNEBvVQ>? MVu8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOTl{NkG5NUc,OjF7Mk[xPVE9N2F-
MTC-TT NULuSXFjT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NGi0S4VKSzVyPUCuNFQhMyByLkCzJO69VQ>? M3[3NVxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJzNEewPVk2Lz5{MUS3NFk6PTxxYU6=
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Nthy-ori 3-1 M{KxZ2N6fG:2b4jpZ4l1gSCjc4PhfS=> M{TkblExKGSjeYO= NHX1N2dEgXSxdH;4bYNqfHliYXfhbY5{fCCqdX3hckBPfGi7LX;ybUA{NTFiY3XscJMh[W[2ZYKgNVAh\GG7czDifUBOXFRiYYPzZZktKEeLNUCgQUA1Njl|IN88UU4> NVjIUm1KRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMk[2OVI5PjBpPkK2OlUzQDZyPD;hQi=>
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
p-MET(Y1234/1235) / MET / p-EGFR(Y1068) / EGFR / p-Gab1(Y627) / Gab1 / p-AKT(S473) / p-ERK / p-EIF4E; 

PubMed: 29188469     


MET kinase inhibitors but not emibetuzumab inhibited MET signaling pathway in Hs746t cells in vitro by western blot analysis. Hs746t cells were treated for 24 h with 133 nM (20 μg/ml) or 667 nM (100 μg/ml) emibetuzumab or MET kinase inhibitors (merestinib, PF04217903, crizotinib, cabozantinib) at 15.6, 62.5, 250 or 1000 nM.

p-MET / p-ERK / p-AKT; 

PubMed: 29520051     


Western blot analysis of cellular pathways modifications after CBZ 5 μM treatment in HOS, MG-63, Saos-2 and U-2 OS cells; (A) CBZ 5 μM inhibits c-MET phosphorilation after 1 hour of treatment; downstream ERK activation kinetic adopts a sigmoidal shape in all OS cell lines, whereas AKT activation is strongly inhibited in HOS, Saos-2 and U-2OS, but not in MG-63 cells.

29188469 29520051
Immunofluorescence
α-tubulin; 

PubMed: 29520051     


Immunostaining of mitotic spindle in control and CBZ 5 μM treated HOS cells using a monoclonal antibody against α-tubulin (in green); white arrows indicate the mitotic spindle poles; control cells show normal bipolar spindles during metaphase formation, whereas treated cells show tripolar spindles during prometaphase (II), metaphase (III) and anaphase (IV); bar scale = 10 μm.

29520051
Growth inhibition assay
Cell viability; 

PubMed: 23661005     


Cells were left untreated or were treated with 5, 7.5 or 10 μM cabozantinib (XL184). Seventy-two hours later viability was detected by MTT-assay and apoptosis by staining with annexinV-FITC followed by FACS-analysis.

23661005
体内研究 XL184按 30 mg/kg 剂量处理携带自发胰岛细胞瘤的RIP-Tag2 小鼠,扰乱 83%肿瘤血管, 降低周细胞和空基底膜袖,引起广泛瘤内缺氧和广泛的肿瘤细胞凋亡,且停药后延缓肿瘤血管再生长,与XL999相比更显著抑制VEGFR而不是c-Met,导致血管降低43%,说明抑制VEGFR,也抑制放大抑制血管新生的其他功能相关的受体酪氨酸激酶(RTK)。XL184也降低原发肿瘤的侵袭和减少转移。[1] XL184 每天按30 mg/kg剂量处理SCID小鼠,显著废除人 MPNST移植瘤生长和转移。[2] XL184 处理乳腺癌,肺癌胶质瘤模型,抑制肿瘤生长,这种作用存在剂量依赖性,降低肿瘤和内皮细胞增殖,促进凋亡。XL184按100 mg/kg 和 10 mg/kg剂量分别单独处理携带MDA-MB-231肿瘤的小鼠和携带C6肿瘤的大鼠,持续抑制肿瘤生长。[3]

推荐的实验操作(此推荐来自于公开的文献所以Selleck并不保证其有效性)

细胞实验: [2]
- 合并
  • Cell lines: ST88-14, STS26T, 和MPNST724
  • Concentrations: 溶于DMSO,终浓度~10 μM
  • Incubation Time: 48小时
  • Method: 使用不同浓度XL184处理细胞48小时。通过MTS实验使用CellTiter96 Aqueous 非放射性细胞增殖实验试剂盒测定细胞生长。然后在 490 nm处测定吸光值。
    (Only for Reference)
动物实验:[1]
- 合并
  • Animal Models: 携带自发胰岛肿瘤的RIP-TAG2转基因小鼠。
  • Dosages: ~60 mg/kg
  • Administration: 口服饲喂
    (Only for Reference)

溶解度 (25°C)

体外 DMSO 100 mg/mL (199.39 mM)
Water Insoluble
Ethanol Insoluble
体内 从左到右依次将纯溶剂加入产品,现配现用(数据来自Selleck实验检测而非文献):
2% DMSO+30% PEG 300+5% Tween 80+ddH2O
5mg/mL

* 溶解度检测是由Selleck技术部门检测的,可能会和文献中提供的溶解度有所差异,这是由于生产工艺和批次不同产生的正常现象。请按照顺序依次加入各个纯溶剂。

化学数据

分子量 501.51
化学式

C28H24FN3O5

CAS号 849217-68-1
储存条件 粉状
溶于溶剂
别名 XL184

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系Selleck为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % ddH2O
计算重置

计算器

摩尔浓度计算器

摩尔浓度计算器

本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系,公式为:

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子量 (g/mol)

摩尔浓度计算公式

  • 质量
    浓度
    体积
    分子量

*在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。

稀释计算器

稀释计算器

用本工具协助配置特定浓度的溶液,使用的计算公式为:

开始浓度 x 开始体积 = 最终浓度 x 最终体积

稀释公式

稀释公式一般简略地表示为: C1V1 = C2V2 ( 输入 输出 )

  • C1
    V1
    C2
    V2

在配置溶液时,请务必参考Selleck产品标签上、MSDS / COA(可在Selleck的产品页面获得)批次特异的分子量使用本工具。.

连续稀释计算器方程

  • 连续稀释

  • 计算结果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量计算器

分子量计算器

通过输入化合物的化学式来计算其分子量:

总分子量:g/mol

注:化学分子式大小写敏感。C10H16N2O2 c10h16n2o2

摩尔浓度计算器

质量 浓度 体积 分子量
计算

临床试验信息

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04631744 Not yet recruiting Drug: Cabozantinib Prostate Cancer Weill Medical College of Cornell University|Exelixis February 15 2021 Phase 2
NCT04551430 Not yet recruiting Drug: Cabozantinib|Drug: Nivolumab|Drug: Ipilimumab Metastatic Soft-tissue Sarcoma Washington University School of Medicine|Exelixis|Bristol-Myers Squibb December 31 2020 Phase 2
NCT04524208 Not yet recruiting Drug: Cabozantinib Neuroendocrine Tumors|Neuroendocrine Carcinoma Karsten Gavenis|University Medical Center Goettingen December 1 2020 Phase 2
NCT04300140 Recruiting Drug: AVB-S6-500|Drug: Cabozantinib (Cabo) Clear Cell Renal Cell Carcinoma Aravive Inc. December 2020 Phase 1|Phase 2
NCT04637204 Recruiting Drug: Cabozantinib|Drug: Axitinib Renal Cell Carcinoma Ipsen November 24 2020 --
NCT04609800 Withdrawn -- Renal Cell Carcinoma Ipsen November 6 2020 --

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID