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

Marta De Donato, Benedetta Righino, Flavia Filippetti, Alessandra Battaglia, Marco Petrillo, Davide Pirolli, Giovanni Scambia, Maria Cristina De Rosa, Daniela Gallo

Research output: Contribution to journalArticle

2 Citations (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.

Original languageEnglish
Article number16047
JournalScientific Reports
Volume8
Issue number1
DOIs
Publication statusPublished - Dec 1 2018

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Mitosis
Phosphotransferases
Genes
Neoplasms
Cell Cycle Checkpoints
Inhibitory Concentration 50
Carcinogenesis
Adenosine Triphosphate
Ligands
Cell Line
Pharmaceutical Preparations
Therapeutics

ASJC Scopus subject areas

  • General

Cite this

De Donato, M., Righino, B., Filippetti, F., Battaglia, A., Petrillo, M., Pirolli, D., ... Gallo, D. (2018). Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. Scientific Reports, 8(1), [16047]. https://doi.org/10.1038/s41598-018-34471-y

Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. / De Donato, Marta; Righino, Benedetta; Filippetti, Flavia; Battaglia, Alessandra; Petrillo, Marco; Pirolli, Davide; Scambia, Giovanni; De Rosa, Maria Cristina; Gallo, Daniela.

In: Scientific Reports, Vol. 8, No. 1, 16047, 01.12.2018.

Research output: Contribution to journalArticle

De Donato, M, Righino, B, Filippetti, F, Battaglia, A, Petrillo, M, Pirolli, D, Scambia, G, De Rosa, MC & Gallo, D 2018, 'Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6', Scientific Reports, vol. 8, no. 1, 16047. https://doi.org/10.1038/s41598-018-34471-y
De Donato M, Righino B, Filippetti F, Battaglia A, Petrillo M, Pirolli D et al. Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. Scientific Reports. 2018 Dec 1;8(1). 16047. https://doi.org/10.1038/s41598-018-34471-y
De Donato, Marta ; Righino, Benedetta ; Filippetti, Flavia ; Battaglia, Alessandra ; Petrillo, Marco ; Pirolli, Davide ; Scambia, Giovanni ; De Rosa, Maria Cristina ; Gallo, Daniela. / Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
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