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.

Rango, E., Di Maria, S., Zamperini, C., Poggialini, F., Crespan, E., Perini, C., et al. (2023). Tyrosine kinase inhibitor Si409 has in vitro and in vivo anti-tumor activity against diffuse large B-cell lymphoma. PHARMACEUTICAL CHEMISTRY JOURNAL, 56(12), 1616-1626 [10.1007/s11094-023-02836-x].

Tyrosine kinase inhibitor Si409 has in vitro and in vivo anti-tumor activity against diffuse large B-cell lymphoma

Rango E.;Di Maria S.;Zamperini C.;Poggialini F.;Saponara S.;Fusi F.;Dreassi E.
;
Botta M.
2023-01-01

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.
2023
Rango, E., Di Maria, S., Zamperini, C., Poggialini, F., Crespan, E., Perini, C., et al. (2023). Tyrosine kinase inhibitor Si409 has in vitro and in vivo anti-tumor activity against diffuse large B-cell lymphoma. PHARMACEUTICAL CHEMISTRY JOURNAL, 56(12), 1616-1626 [10.1007/s11094-023-02836-x].
File in questo prodotto:
File Dimensione Formato  
Tyrosine Kinase Inhibitor-Rango-2023.pdf

non disponibili

Descrizione: Articolo
Tipologia: PDF editoriale
Licenza: NON PUBBLICO - Accesso privato/ristretto
Dimensione 2.18 MB
Formato Adobe PDF
2.18 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11365/1232445