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.;Crespan E.;Saponara S.;Fusi F.;Maga G.;Berton 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
https://hdl.handle.net/11365/1232445
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