Cabozantinib (XL184, BMS-907351) (Synonyms: BMS-907351, Cabozantinib) |
| Catalog No.GC15779 |
Cabozantinib (XL184, BMS-907351) es un inhibidor novedoso de MET y VEGFR2 que inhibe simultáneamente la metástasis, la angiogénesis y el crecimiento tumoral.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 849217-68-1
Sample solution is provided at 25 µL, 10mM.
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Cabozantinib (XL184, BMS-907351) es un inhibidor novedoso de MET y VEGFR2 que inhibe simultáneamente la metástasis, la angiogénesis y el crecimiento tumoral[1]. Sus valores de IC50 para VEGFR2 y c-Met son 0.035 nM y 1,3 nM[2].
El tratamiento con Cabozantinib (XL184) de cultivos MAME de células MDA-MB-231 y HCC70 (fibroblastos que expresan HGF) fue citotóxico y redujo significativamente los crecimientos invasivos multicelulares, incluso en cultivos con fibroblastos que expresan HGF[3]. El estrés celular inducido por Cabozantinib resultó en la inducción de ICD (un tipo peculiar de apoptosis) en la línea celular DU-145[4]. Se ha informado que Cabozantinib inhibe la expresión de MMP-1 bloqueando la vía de señalización HGF-MET en células de cáncer de vejiga[5]. MMP-1 disminuyó significativamente en células de ESCC tratadas con cabozantinib, lo que fue la razón de la disminución de la actividad migratoria de las células de ESCC tratadas con cabozantinib[6].
Cabozantinib inhibe el crecimiento tumoral de manera dependiente de la dosis en modelos de tumores humanos en roedores[1]. Estudios farmacodinámicos in vivo mostraron una inhibición sustancial de RET en tumores xenoinjertados TT tras una dosis oral única de cabozantinib[7]. Cabozantinib mostró excelentes efectos antitumorales in vivo utilizando un modelo de explantes de CRC (cáncer colorrectal)[8].
References:
[1]. Yakes F Michael,Chen Jason, et al. Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth.[J]. Molecular cancer therapeutics,2011,10(12).
[2]. Weon-Kyoo You, Barbara Sennino, et al. VEGF and c-Met Blockade Amplify Angiogenesis Inhibition in Pancreatic Islet Cancer[J]. Microenvironment and Immunology,2011.
[3]. Sameni Mansoureh,Tovar Elizabeth A, et al. Cabozantinib (XL184) Inhibits Growth and Invasion of Preclinical TNBC Models.[J]. Clinical cancer research : an official journal of the American Association for Cancer Research,2016,22(4).
[4] Scirocchi Fabio,Napoletano Chiara,et al. Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib[J]. Frontiers in Oncology,2021,11.
[5] Shintani T, Kusuhara Y, et al. The involvement of hepatocyte growth factor-MET-matrix metalloproteinase 1 signaling in bladder cancer invasiveness and proliferation. Effect of the MET inhibitor, cabozantinib (XL184), on bladder cancer cells. Urology. (2017) 101:169.e7-13. doi: 10.1016/j.urology.2016.12.006.
[6] Pei-Wen Yang, Yu-Cheng Liu, et al. Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)[J]. Frontiers in Oncology, 2019.
[7] Bentzien Frauke,Zuzow Marcus, 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.[J]. Thyroid : official journal of the American Thyroid Association,2013,23(12).
[8] Scott Aaron J,Arcaroli John J,et al. Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms.[J]. Molecular cancer therapeutics,2018,17(10).
| Experimento celular [1]: | |
Líneas celulares | Líneas celulares DU-145 |
Método de preparación | Las células DU145 fueron marcadas con éster succinimidil de carboxifluoresceína (CFSE) (1 µM) y se incubaron durante 20 minutos a 37°C, protegiéndolas de la luz. Después de dos lavados con PBS (37°C), las células fueron tratadas con 2.5 mg/ml de Cabozantinib (XL184). |
Condiciones de reacción | 2.5 mg/ml, 48h |
Aplicaciones | Las líneas celulares DU-145 expresaron MET, y el tratamiento con Cabozantinib (XL184) tuvo un efecto citostático, bloqueando las células en la fase G1. Cabozantinib (XL184) indujo una inhibición de la vía autofágica en las células DU-145, a través de una regulación al alza del complejo mTOR. Esto puede estar relacionado con la alta expresión de AXL observada en DU-145; este también es un objetivo RTK para Cabozantinib (XL184). |
| Experimento animal [2]: | |
Modelos animales | Ratones machos NOD-SCID de 6 a 8 semanas de edad |
Forma de dosificación | 30 mg/kg/día, por gavage oral |
Aplicaciones | La expresión de la metaloproteinasa de matriz-1 (MMP-1), un factor crucial en la migración celular, disminuyó marcadamente en los ratones tratados con cabozantinib (XL 184) en comparación con el grupo de vehículo. |
Referencias: [1]. Scirocchi Fabio, Napoletano Chiara, et al. Immunogenic Cell Death and Immunomodulatory Effects of Cabozantinib[J]. Frontiers in Oncology, 2021, 11. [2]. Pei-Wen Yang, Yu-Cheng Liu, et al. Cabozantinib (XL184) and R428 (BGB324) Inhibit the Growth of Esophageal Squamous Cell Carcinoma (ESCC)[J]. Frontiers in Oncology, 2019. | |
| Cas No. | 849217-68-1 | SDF | |
| Sinónimos | BMS-907351, Cabozantinib | ||
| Chemical Name | 1-N-[4-(6,7-dimethoxyquinolin-4-yl)oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide | ||
| 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 | ||
| Formula | C28H24FN3O5 | M.Wt | 501.51 |
| Solubility | ≥ 25.1mg/mL in DMSO | Storage | 4°C, protect from light |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.994 mL | 9.9699 mL | 19.9398 mL |
| 5 mM | 398.8 μL | 1.994 mL | 3.988 mL |
| 10 mM | 199.4 μL | 997 μL | 1.994 mL |
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Quality Control & SDS
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- Purity: >99.50%
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Average Rating: 5 (Based on Reviews and 8 reference(s) in Google Scholar.)
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