Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6

Giovanni Scambia, Benedetta Righino, Flavia Filippetti, Marco Petrillo, Davide Pirolli, Maria Cristina De Rosa

Risultato della ricerca: Contributo in rivistaArticolo in rivista

9 Citazioni (Scopus)

Abstract

The NIMA (never in mitosis, gene A)-related kinase-6 (NEK6), which is implicated in cell cycle control and plays significant roles in tumorigenesis, is an attractive target for the development of novel anti-cancer drugs. Here we describe the discovery of a potent ATP site-directed inhibitor of NEK6 identified by virtual screening, adopting both structure- and ligand-based techniques. Using a homology-built model of NEK6 as well as the pharmacophoric features of known NEK6 inhibitors we identified novel binding scaffolds. Twenty-five compounds from the top ranking hits were subjected to in vitro kinase assays. The best compound, i.e. compound 8 ((5Z)-2-hydroxy-4-methyl-6-oxo-5-[(5-phenylfuran-2-yl)methylidene]-5,6-dihydropyridine-3-carbonitrile), was able to inhibit NEK6 with low micromolar IC50 value, also displaying antiproliferative activity against a panel of human cancer cell lines. Our results suggest that the identified inhibitor can be used as lead candidate for the development of novel anti-cancer agents, thus opening the possibility of new therapeutic strategies.
Lingua originaleEnglish
pagine (da-a)1-13
Numero di pagine13
RivistaScientific Reports
Volume8
DOI
Stato di pubblicazionePubblicato - 2018

Keywords

  • Multidisciplinary

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