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

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.