Maria Gabriella Brasca
Pfizer
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Publication
Featured researches published by Maria Gabriella Brasca.
Biochemical Pharmacology | 2012
Simona Caporali; Ester Alvino; Lauretta Levati; Alessia Isabella Esposito; Marina Ciomei; Maria Gabriella Brasca; Donatella Del Bufalo; Marianna Desideri; Enzo Bonmassar; Ulrich Pfeffer; Stefania D’Atri
We previously demonstrated that PHA-848125, a cyclin-dependent kinase inhibitor presently under Phase II clinical investigation, impairs melanoma cell growth. In this study, gene expression profiling showed that PHA-848125 significantly modulated the expression of 128 genes, predominantly involved in cell cycle control, in the highly drug-sensitive GL-Mel (p53 wild-type) melanoma cells. Up-regulation of 4 selected genes (PDCD4, SESN2, DDIT4, DEPDC6), and down-regulation of 6 selected genes (PTTG1, CDC25A, AURKA, AURKB, PLK1, BIRC5) was confirmed at protein levels. The same protein analysis performed in PHA-848125-treated M10 melanoma cells - p53 mutated and less sensitive to the drug than GL-Mel cells - revealed no DEPDC6 expression and no changes of PTTG1, PDCD4 and BIRC5 levels. Upon PHA-848125 treatment, a marked PTTG1 down-modulation was also observed in A375 cells (p53 wild-type) but not in CN-Mel cells (p53 mutated). PTTG1 silencing significantly inhibited melanoma cell proliferation and induced senescence, with effects less pronounced in p53 mutated cells. PTTG1 silencing increased PHA-848125 sensitivity of p53 mutated cells but not that of A375 or GL-Mel cells. Accordingly, in M10 but not in A375 cells a higher level of senescence was detected in PHA-848125-treated/PTTG1-silenced cells with respect to PHA-848125-treated controls. In A375 and GL-Mel cells, TP53 silencing attenuated PHA-848125-induced down-modulation of PTTG1 and decreased cell sensitivity to the drug. These findings indicate that PHA-848125-induced down-regulation of PTTG1 depends, at least in part, on p53 function and contributes to the antiproliferative activity of the drug. Our study provides further molecular insight into the antitumor mechanism of PHA-848125.
Bioorganic & Medicinal Chemistry | 2014
Maria Gabriella Brasca; Marcella Nesi; Nilla Avanzi; Dario Ballinari; Tiziano Bandiera; Jay Aaron Bertrand; Simona Bindi; Giulia Canevari; Davide Carenzi; Daniele Casero; Lucio Ceriani; Marina Ciomei; Alessandra Cirla; Maristella Colombo; Sabrina Cribioli; Cinzia Cristiani; Franco Della Vedova; Gabriele Fachin; Marina Fasolini; Eduard R. Felder; Arturo Galvani; Antonella Isacchi; Danilo Mirizzi; Ilaria Motto; Achille Panzeri; Enrico Pesenti; Paola Vianello; Paola Gnocchi; Daniele Donati
We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile.
Journal of Medicinal Chemistry | 2004
Paolo Pevarello; Maria Gabriella Brasca; Raffaella Amici; Paolo Orsini; Gabriella Traquandi; Luca Corti; Claudia Piutti; Pietro Sansonna; Manuela Villa; Betsy S. Pierce; Maurizio Pulici; Patrizia Giordano; Katia Martina; Edward L. Fritzen; Richard A. Nugent; Elena Casale; Alexander D. Cameron; Marina Ciomei; Fulvia Roletto; Antonella Isacchi; Gianpaolo Fogliatto; Enrico Pesenti; Wilma Pastori; Aurelio Marsiglio; Karen L. Leach; Paula Munns Clare; Francesco Fiorentini; Mario Varasi; and Anna Vulpetti; Martha A. Warpehoski
Archive | 2001
Antonio Longo; Maria Gabriella Brasca; Paolo Orsini; Gabriella Traquandi; Valeria Pittalà; Anna Vulpetti; Mario Varasi; Paolo Pevarello
Journal of the American Chemical Society | 2007
Gianluca Papeo; Patrizia Giordano; Maria Gabriella Brasca; Ferdinando Buzzo; Dannica Caronni; Franco Ciprandi; Nicola Mongelli; Marina Veronesi; and Anna Vulpetti; Claudio Dalvit
Archive | 2004
Barbara Salom; Matteo D'anello; Maria Gabriella Brasca; Patrizia Giordano; Katia Martina; Francesco Angelucci; Frederick Arthur Brookfield; William John Trigg; Edward Andrew Boyd; Jonathan Anthony Larard
Archive | 2006
Ermes Vanotti; Francesco Angelucci; Alberto Bargiotti; Maria Gabriella Brasca; Antonella Ermoli; Maria Menichincheri
Archive | 2002
Paolo Pevarello; Raffaella Amici; Manuela Villa; Barbara Salom; Anna Vulpetti; Mario Varasi; Maria Gabriella Brasca; Gabriella Traquandi; Marcella Nesi
ChemInform | 2000
Paolo Pevarello; Raffaella Amici; Maria Gabriella Brasca; Manuela Villa; Mario Varasi
Archive | 2010
Barbara Salom; Matteo D'anello; Maria Gabriella Brasca; Patrizia Giordano; Katia Martina; Francesco Angelucci; Frederick Arthur Brookfield; William John Trigg; Edward Andrew Boyd; Jonathan Anthony Larard