(5Z)-2-hydroxy-4-methyl-6-oxo-5-[(5-phenylfuran-2-yl)methylidene]-5,6-dihydropyridine-3-carbonitrile

ZINC05007751 is a potent NIMA-related kinase NEK6 inhibitor with an IC50 of 3.4 μM. ZINC05007751 shows antiproliferative activity against a panel of human cancer cell lines, and displays a synergistic effect with Cisplatin and Paclitaxel in a BRCA2 mutated ovarian cancer cell line. ZINC05007751 is very selective against NEK1 and NEK6 with no significant activity was observed against NEK2, NEK7, and NEK9[1]. ZINC05007751 (6 μM-190 μM; 24 hours) inhibits the growth of MDA-MB-231, PEO1, NCI-H1299 and HCT-15 with IC50 below 100 μM[1].ZINC05007751 induces perturbation of PEO1 cell cycle[1].ZINC05007751 (ovarian cancer cells PEO1) shows synergism with Cisplatin, resulting in a significant reduction of Cisplatin IC50 from 7.9 to 0.1 μM, with combination ZINC05007751 (44 μM) + Cisplatin (10 μM) exhibiting the greatest synergistic effect[1].

[1]. De Donato M, et al. Identification and antitumor activity of a novel inhibitor of the NIMA-related kinase NEK6. Sci Rep. 2018;8(1):16047. Published 2018 Oct 30.