http://www.cnr.it/ontology/cnr/individuo/prodotto/ID329563

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 (Articolo in rivista)

Type

Label

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 (Articolo in rivista) (literal)

Anno

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi

Alternative label

Tintori C, Fallacara AL, Radi M, Zamperini C, Dreassi E, Crespan E, Maga G, Schenone S, Musumeci F, Brullo C, Richters A, Gasparrini F, Angelucci A, Festuccia C, Delle Monache S, Rauh D, Botta M. (2015)
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
in Journal of medicinal chemistry
(literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori

Tintori C, Fallacara AL, Radi M, Zamperini C, Dreassi E, Crespan E, Maga G, Schenone S, Musumeci F, Brullo C, Richters A, Gasparrini F, Angelucci A, Festuccia C, Delle Monache S, Rauh D, Botta M. (literal)

Pagina inizio

Pagina fine

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#url

http://www.scopus.com/inward/record.url?eid=2-s2.0-84920848622&partnerID=q2rCbXpz (literal)

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume

Rivista

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroFascicolo

Note

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni

Dipartimento di Biotecnologie, Chimica e Farmacia, Università Degli Studi di Siena, Via Aldo Moro 2, Siena, 53100, Italy; Dipartimento di Chimica e Tecnologie Farmaceutiche, Sapienza Università di Roma, Piazzale Aldo Moro 5, Rome, 00185, Italy; Istituto di Genetica Molecolare, IGM-CNR, Via Abbiategrasso 207, Pavia, 27100, Italy; Dipartimento di Farmacia, Università Degli Studi di Genova, Viale Benedetto XV, 3, Genova, 16132, Italy; Department of Chemistry and Chemical Biology, Technical University of Dortmund, Otto-Hahn-Strasse 6, Dortmund, 44227, Germany; Dipartimento di Medicina Molecolare, Sapienza Università di Roma, Piazzale Aldo Moro 5, Rome, 00185, Italy; Dipartimento di Scienze Cliniche Applicate e Biotecnologiche, Università Degli Studi dell'Aquila, Via Vetoio, Coppito, L'Aquila, 67100, Italy; Sbarro Institute for Cancer Research and Molecular Medicine, College of Science and Technology, Temple University, 1900 North 12th Street, Philadelphia, PA, 19122, United States; Dipartimento di Farmacia, University of Parma, Parco Area delle Scienze 27/A, Parma, 43124, Italy (literal)

Titolo

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 (literal)

Abstract

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]pyrimidine 3 was reported as a dual c-Src/Abl inhibitor. Herein we describe a multidisciplinary drug discovery approach for the optimization of the lead 3 against c-Src. Starting from the X-ray crystal structure of c-Src in complex with 3, Monte Carlo free energy perturbation calculations were applied to guide the design of c-Src inhibitors with improved activities. As a result, the introduction of a meta hydroxyl group on the C4 anilino ring was computed to be particularly favorable. The potency of the synthesized inhibitors was increased with respect to the starting lead 3. The best identified compounds were also found active in the inhibition of neuroblastoma cell proliferation. Furthermore, compound 29 also showed in vivo activity in xenograft model using SH-SY5Y cells. (literal)

Prodotto di

Autore CNR

Prodotto

Autore CNR di

Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#rivistaDi

data.CNR.it