English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/225612
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE
Exportar a otros formatos:


Sunitinib-Containing Carborane Pharmacophore with the Ability to Inhibit Tyrosine Kinases Receptors FLT3, KIT and PDGFR-β, Exhibits Powerful In Vivo Anti-Glioblastoma Activity

AuthorsAlamón, Catalina; Dávila, Belén; García, María Fernanda; Sánchez, Carina; Kovacs, Mariángeles; Trias, Emiliano; Barbeito, Luis; Gabay, Martín; Zeineh, Nidal; Gavish, Moshe; Teixidor, Francesc ; Viñas, Clara ; Couto, Marcos; Cerecetto, Hugo
Sub-G1 arrest
Anti-tumor activity
Issue Date18-Nov-2020
PublisherMultidisciplinary Digital Publishing Institute
CitationCancers 12(11): 3423 (2020)
AbstractMalignant gliomas are the most common malignant and aggressive primary brain tumors in adults, the prognosis being—especially for glioblastomas—extremely poor. There are no effective treatments yet. However, tyrosine kinase receptor (TKR) inhibitors and boron neutron capture therapy (BNCT), together, have been proposed as future therapeutic strategies. In this sense in our ongoing project of developing new anti-glioblastoma drugs, we identified a sunitinib-carborane hybrid agent, <b>1</b>, with both in vitro selective cytotoxicity and excellent BNCT-behavior. Consequently, we studied the ability of compound <b>1</b> to inhibit TKRs, its promotion of cellular death processes, and its effects on the cell cycle. Moreover, we analyzed some relevant drug-like properties of <b>1</b>, i.e., mutagenicity and ability to cross the blood–brain barrier. These results encouraged us to perform an in vivo anti-glioblastoma proof of concept assay. It turned out to be a selective FLT3, KIT, and PDGFR-β inhibitor and increased the apoptotic glioma-cell numbers and arrested sub-G1-phase cell cycle. Its in vivo activity in immunosuppressed mice bearing U87 MG human glioblastoma evidenced excellent anti-tumor behavior.
Identifiersdoi: 10.3390/cancers12113423
Appears in Collections:(ICMAB) Artículos
Files in This Item:
File Description SizeFormat 
cancers-12-03423-v2.pdf5,47 MBAdobe PDFThumbnail
Show full item record
Review this work

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.