| Literature DB >> 25009002 |
Maria Gabriella Brasca1, Marcella Nesi2, Nilla Avanzi2, Dario Ballinari2, Tiziano Bandiera2, Jay Bertrand2, Simona Bindi2, Giulia Canevari2, Davide Carenzi2, Daniele Casero2, Lucio Ceriani2, Marina Ciomei2, Alessandra Cirla2, Maristella Colombo2, Sabrina Cribioli2, Cinzia Cristiani2, Franco Della Vedova2, Gabriele Fachin2, Marina Fasolini2, Eduard R Felder2, Arturo Galvani2, Antonella Isacchi2, Danilo Mirizzi2, Ilaria Motto2, Achille Panzeri2, Enrico Pesenti2, Paola Vianello2, Paola Gnocchi2, Daniele Donati2.
Abstract
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.Entities:
Keywords: Anti-cancer agents; JAK2; Myeloproliferative disorders; Protein kinase inhibitor; Tumour cell proliferation inhibition
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Year: 2014 PMID： 25009002 DOI： 10.1016/j.bmc.2014.06.025
Source DB: PubMed Journal: Bioorg Med Chem ISSN： 0968-0896 Impact factor: 3.641