학술논문
Tyrosine Kinase Inhibitor Si409 Has In Vitro and In Vivo Anti-Tumor Activity Against Diffuse Large B-Cell Lymphoma.
Document Type
Article
Author
Rango, Enrico; Di Maria, Salvatore; Zamperini, Claudio; Poggialini, Federica; Crespan, Emmanuele; Perini, Cecilia; Sabetta, Samantha; Saponara, Simona; Fusi, Fabio; Maga, Giovanni; Angelucci, Adriano; Gaudio, Eugenio; Berton, Francesco; Schenone, Silvia; Botta, Lorenzo; Dreassi, Elena; Botta, Maurizio
Source
Subject
*DIFFUSE large B-cell lymphomas
*PROTEIN-tyrosine kinase inhibitors
*ANTINEOPLASTIC agents
*ANAPLASTIC lymphoma kinase
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Language
ISSN
0091-150X
Abstract
The abnormal activation of Src family kinases (SFKs) due to deregulation of the B-cell receptor (BCR) signalling pathway provides a promising target for development of new pharmacological strategy to overcome the ibrutinib resistance in diffuse large B-cell lymphoma (DLBCL). In this work, we demonstrated that Si409, a pyrazolo[3,4-d]pyrimidine-based compound, has the ability to inhibit key members of SFKs and to reduce the proliferation of several B-cell tumor cell lines. Preclinical cytotoxicity profile, in vivo pharmacokinetic (PK) properties, and therapeutic efficacy in subcutaneous murine DLBCL model have been evaluated. Results obtained through these preliminary analyses revealed a promising role of Si409 and suggested its further development for the treatment of DLBCL. [ABSTRACT FROM AUTHOR]