- Combining X-ray crystallography and molecular modeling toward the optimization of pyrazolo[3,4-d ]pyrimidines as potent c-Src inhibitors active in vivo against neuroblastoma
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c-Src is a tyrosine kinase belonging to the Src-family kinases. It is overexpressed and/or hyperactivated in a variety of cancer cells, thus its inhibition has been predicted to have therapeutic effects in solid tumors. Recently, the pyrazolo[3,4-d]pyrimi
- Tintori, Cristina,Fallacara, Anna Lucia,Radi, Marco,Zamperini, Claudio,Dreassi, Elena,Crespan, Emmanuele,Maga, Giovanni,Schenone, Silvia,Musumeci, Francesca,Brullo, Chiara,Richters, André,Gasparrini, Francesca,Angelucci, Adriano,Festuccia, Claudio,Delle Monache, Simona,Rauh, Daniel,Botta, Maurizio
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p. 347 - 361
(2015/02/19)
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- Exploring the chemical space around the privileged pyrazolo[3,4-d] pyrimidine scaffold: Toward novel allosteric inhibitors of T315I-mutated Abl
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A library of pyrazolo[3,4-d]pyrimidines, endowed with a high level of molecular diversity, has been developed applying a synthetic sequence that allowed C3, N1, C4, and C6 substitution. The enzymatic screening of this "privileged scaffold"-based compound collection, validated the use of a diversity-oriented approach in a field characteristically explored by target-oriented synthesis. In fact, several compounds showed high activity against the selected kinases (i.e., Src, Abl wt, and T315I mutated-form), furthermore and interestingly a new compound has emerged as an allosteric inhibitor of the T315I mutated-form of Abl, opening up new opportunities for the development of a novel class of noncompetitive inhibitors of Abl (T315I).
- Vignaroli, Giulia,Mencarelli, Martina,Sementa, Deborah,Crespan, Emmanuele,Kissova, Miroslava,Maga, Giovanni,Schenone, Silvia,Radi, Marco,Botta, Maurizio
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supporting information
p. 168 - 175
(2014/05/06)
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- Identification of potent c-Src inhibitors strongly affecting the proliferation of human neuroblastoma cells
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Neuroblastoma (NB) represents the most common extracranial paediatric solid tumor for which no specific FDA-approved treatment is currently available. The tyrosine kinase c-Src has been reported to play an important role in the differentiation, cell-adhes
- Radi, Marco,Brullo, Chiara,Crespan, Emmanuele,Tintori, Cristina,Musumeci, Francesca,Biava, Mariangela,Schenone, Silvia,Dreassi, Elena,Zamperini, Claudio,Maga, Giovanni,Pagano, Dafne,Angelucci, Adriano,Bologna, Mauro,Botta, Maurizio
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p. 5928 - 5933
(2011/10/18)
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