2. Academic Validation
  3. Identification of a novel pyrazolo[3,4-d]pyrimidine able to inhibit cell proliferation of a human osteogenic sarcoma in vitro and in a xenograft model in mice

Identification of a novel pyrazolo[3,4-d]pyrimidine able to inhibit cell proliferation of a human osteogenic sarcoma in vitro and in a xenograft model in mice

  • J Med Chem. 2007 Nov 15;50(23):5579-88. doi: 10.1021/jm061449r.
Fabrizio Manetti 1,  Annalisa Santucci,  Giada A Locatelli,  Giovanni Maga,  Adriano Spreafico,  Tommaso Serchi,  Maurizio Orlandini,  Giulia Bernardini,  Nicola P Caradonna,  Andrea Spallarossa,  Chiara Brullo,  Silvia Schenone,  Olga Bruno,  Angelo Ranise,  Francesco Bondavalli,  Oskar Hoffmann,  Mauro Bologna,  Adriano Angelucci,  Maurizio Botta
Affiliations

Affiliation

  • 1 Dipartimento Farmaco Chimico Tecnologico, Università degli Studi di Siena, Siena, Italy.
PMID: 17929792 DOI: 10.1021/jm061449r
Abstract

New pyrazolo[3,4-d]pyrimidines were synthesized and found to inhibit Src phosphorylation in a cell-free assay. Some of them significantly reduced the growth of human osteogenic sarcoma (SaOS-2) cells. The best compound, in terms of inhibitory properties toward both Src and SaOS-2 cells, was further investigated and found to reduce bone resorption when used to treat mouse osteoclasts, without interfering with normal osteoblast growth. Moreover, its metabolic stability prompted its study on a human SaOS-2 xenograft tumor model in nude mice, where the compound reduced significantly both the volume and weight of the tumor. These experimental findings make the new compound an interesting hit in the field of bone-related diseases.

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