Identification and Biological Characterization of the Pyrazolo[3,4-d]pyrimidine Derivative SI388 Active as Src Inhibitor

Src is a non-receptor tyrosine kinase (TK) whose involvement in cancer, including glioblastoma (GBM), has been extensively demonstrated. In this context, we started from our in-house library of pyrazolo[3,4-d]pyrimidines that are active as and/or Bcr-Abl TK inhibitors and performed lead optimization study to discover new generation derivative suitable for targeting. We synthesized 19 compounds, 2a-s. Among these, compound 2a (SI388) was identified the most potent inhibitor. Based on cell-free results, investigated effect SI388 2D 3D GBM cellular models. Interestingly, significantly inhibits kinase, therefore affects cell viability, tumorigenicity enhances cancer sensitivity ionizing radiation.