• 欢迎来到美国APExBIO中文站,专注小分子抑制剂、激动剂、拮抗剂及化合物库!

 


加 微 信 得 红 包
ApexBio
Search Site
首页 >> Signaling Pathways >> Tyrosine Kinase >> FLT3 >> Cabozantinib (XL184, BMS-907351)
相关产品
Cabozantinib (XL184, BMS-907351)
VEGFR2/Met/Ret/Kit/FLT/AXL抑制剂

Cabozantinib (XL184, BMS-907351)

产品编号:A2977
ApexBio 的所有产品仅用作科研,我们不为任何个人用途提供产品和服务
规格 单价 库存 订购数量
10mM (in 1mL DMSO) ¥750.00 现货
5mg ¥700.00 现货
25mg ¥2,000.00 现货
100mg ¥6,800.00 现货

电话: 021-55669583

Email: sales@apexbio.cn

全球经销商

Sample solution is provided at 25 µL, 10mM.

质量控制

化学结构

Cabozantinib (XL184, BMS-907351)

相关生物数据

Cabozantinib (XL184, BMS-907351)

相关生物数据

Cabozantinib (XL184, BMS-907351)

Cabozantinib (XL184, BMS-907351) Dilution Calculator

Concentration (start)
x
Volume (start)
=
Concentration (final)
x
Volume (final)
 
 
 
C1
V1
C2
V2

calculate

Cabozantinib (XL184, BMS-907351) Molarity Calculator

Mass
=
Concentration
x
Volume
x
MW*
 
 
 
g/mol

calculate

化学性质

CAS号 849217-68-1 SDF Download SDF
化学名 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
SMILES COC1=CC2=C(C=CN=C2C=C1OC)OC3=CC=C(C=C3)NC(=O)C4(CC4)C(=O)NC5=CC=C(C=C5)F
分子式 C28H24FN3O5 分子量 501.51
溶解度 ≥25.1mg/mL in DMSO 储存条件 Store at -20°C
物理性状 A solid 运输条件 试用装:蓝冰运输。
其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议 为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

生物活性

Description Cabozantinib (XL184, BMS-907351)是一种有效的VEGFR2抑制剂,IC50值为0.035 nM,也抑制c-Met、Ret、Kit、Flt-1/3/4、Tie2和AXL,IC50值为1.3 nM、4 nM、4.6 nM、12 nM/11.3 nM/6 nM、14.3 nM和7 nM。
靶点 VEGFR2 c-Met Ret c-Kit Flt-1/3/4 Tie2
IC50 0.035 nM 1.3 nM 4 nM 4.6 nM 12 nM/11.3 nM/6 nM 14.3 nM

实验操作

细胞实验[1]:

细胞系

人类微血管内皮细胞(HMVEC)

溶解方法

该化合物在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月

反应条件

IC50: 6.7 nM,7天

实验结果

在cabozantinib存在的情况下,使用VEGF孵育HMVEC细胞,针对CD31的免疫染色可以观察到小管形成。Cabozantinib抑制小管形成,IC50值为6.7 nM,目前没有证据表明该药物有细胞毒性,这表明cabozantinib具有抗血管生成作用而没有细胞毒性。

动物实验[1]:

动物模型

植入H441细胞的雌性nu/nu小鼠

剂量

口服给药,100 mg/kg,8 hours

实验结果

在具有组成性磷酸化MET的H441肿瘤中,口服单一剂量100mg/kg的cabozantinib,给药2至8小时后,MET的磷酸化被抑制,治疗后48小时,MET磷酸化恢复到基础水平,说明药物效果是可逆的。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的,属于正常现象。

References:

[1] Yakes F M, Chen J, Tan J, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth. Molecular cancer therapeutics, 2011, 10(12): 2298-2308.

研究更新

1. Multi-targeted tyrosine kinase inhibitors in clinical development: focus on XL-184 (cabozantinib). Drugs Today (Barc). 2011 Nov;47(11):857-68. doi: 10.1358/dot.2011.47.11.1688487.
Abstract
XL-184 is an inhibitor of multiple receptor tyrosine kinases, particularly Met, VEGFR-2 and Ret, with clinical activities against tumors of both epithelial and mesenchymal origins, particularly medullary thyroid cancer and cancers metastatic to the bone.
3. Cabozantinib inhibits prostate cancer growth and prevents tumor-induced bone lesions. Clin Cancer Res. 2014 Feb 1;20(3):617-30. doi: 10.1158/1078-0432.CCR-13-0839. Epub 2013 Oct 4.
Abstract
XL-184, a multi-tyrosine kinase inhibitor targeting MET and VEGFR2, induces resolution of bone scan lesions in men with castration-resistant prostate cancer bone metastases possibly through a direct antitumor activity, modulating bone, or both.
4. A dose-ranging study of cabozantinib in men with castration-resistant prostate cancer and bone metastases. Clin Cancer Res. 2013 Jun 1;19(11):3088-94. doi: 10.1158/1078-0432.CCR-13-0319. Epub 2013 Apr 3.
Abstract
The efficacy and tolerability of XL-184, a MET/VEGFR2 inhibitor improving bone scans in mCRPC patients, at lower starting doses were determined due to XL-184 induced AE.
5. In Vitro and In Vivo Activity of Cabozantinib (XL184), an Inhibitor of RET, MET, and VEGFR2, in a Model of Medullary Thyroid Cancer. Thyroid. 2013 Dec;23(12):1569-77. doi: 10.1089/thy.2013.0137. Epub 2013 Sep 17.
Abstract
XL-184, a multi-tyrosine kinase inhibitor targeting RET, MET and VEGFR2, inhibited activated RET mutations associated with MTC and effectively suppressed the growth of MTC tumor cell models both in vivo and in vitro.

产品描述

Cabozantinib(XL184,BMS-907351[1])是多种受体酪氨酸激酶(RTKs)的抑制剂,包括血管内皮生长因子受体2(VEGFR2)、肝细胞生长因子受体(MET)和转染重排酪氨酸激酶(RET)[2][3],IC50值分别为0.035 nmol/L、1.3 nmol/L和5.2 nmol/L[4]。

RTKs传导细胞外的各种信号,用于调节细胞分化和增值。配体结合触发多种事件,如酪氨酸残基的自磷酸化和受体二聚化[5]。

TT细胞系是一种人MTC细胞系,含激活的C634W RET突变,并表达降钙素。在该细胞系中,cabozantinib抑制RET的自磷酸化,IC50值为85 nmol/L。在10%血清中生长72小时的TT细胞中,cabozantinib剂量依赖性地抑制细胞增殖,IC50值为94 nmol/L[4]。

在TT肿瘤异种移植nu/nu小鼠模型中,与对照组相比,cabozantinib以10、30或60 mg/kg的剂量每天口服给药后显著抑制肿瘤生长。与对照组相比,在30和60 mg/kg剂量组,cabozantinib显著减少血清中循环降钙素的水平(75%;p< 0.005)[4]。

参考文献:
[1].  Michael G. Doran, Daniel E. Spratt, John Wongvipat, et al. Cabozantinib Resolves Bone Scans in Tumor-Nave Mice Harboring Skeletal Injuries. Molecular Imaging, 2014, 13:1-5.
[2].  Rossella Elisei, Martin J. Schlumberger, Stefan P. Müller, et al. Cabozantinib in Progressive Medullary Thyroid Cancer. J. Clin. Oncol., 2013, 31(29):3639-46.
[3].  Razelle Kurzrock, Steven I. Sherman, Douglas W. Ball, et al. Activity of XL184 (Cabozantinib), an Oral Tyrosine Kinase Inhibitor, in Patients with Medullary Thyroid Cancer. J. Clin. Oncol., 2011, 29(19):2660-6.
[4].  Frauke Bentzien, Marcus Zuzow, Nathan Heald, et al. In Vitro and In Vivo Activity of Cabozantinib (XL184), an Inhibitor of RET, MET, and VEGFR2, in a Model of Medullary Thyroid Cancer. Thyroid, 2013, 23(12):1569-1577.
[5].  Xianhua Piao, Robert Paulson, Peter vanderGeer, et al. Oncogenic mutation in the Kit receptor tyrosine kinase alters substrate specificity and induces degradation of the protein tyrosine phosphatase SHP-1. Proc. Natl. Acad. Sci. USA., 1996, 93(25):14665-14669.