Cabozantinib (XL184, BMS-907351)
mRNA synthesis
In vitro transcription of capped mRNA with modified nucleotides and Poly(A) tail
Tyramide Signal Amplification (TSA)
TSA (Tyramide Signal Amplification), used for signal amplification of ISH, IHC and IC etc.
Phos Binding Reagent Acrylamide
Separation of phosphorylated and non-phosphorylated proteins without phospho-specific antibody
Cell Counting Kit-8 (CCK-8)
A convenient and sensitive way for cell proliferation assay and cytotoxicity assay
SYBR Safe DNA Gel Stain
Safe and sensitive stain for visualization of DNA or RNA in agarose or acrylamide gels.
Inhibitor Cocktails
Protect the integrity of proteins from multiple proteases and phosphatases for different applications.
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.
Physical Appearance | A solid |
Storage | Store at -20°C |
M.Wt | 501.51 |
Cas No. | 849217-68-1 |
Formula | C28H24FN3O5 |
Solubility | ≥25.08 mg/mL in DMSO; insoluble in H2O; ≥20.65 mg/mL in EtOH |
Chemical Name | 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide |
SDF | Download SDF |
Canonical 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 |
运输条件 | 蓝冰运输或根据您的需求运输。 |
一般建议 | 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。溶液形式一般不宜长期储存,请尽快用完。 |
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. |
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 |
质量控制和MSDS
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