Piperazin-1-ylpyridazine Derivatives Are a Novel Class of Human dCTP Pyrophosphatase 1 Inhibitors

Journal of Medicinal Chemistry
Sabin Llona-MinguezThomas Helleday

Abstract

The dCTP pyrophosphatase 1 (dCTPase) is a nucleotide pool "housekeeping" enzyme responsible for the catabolism of canonical and noncanonical nucleoside triphosphates (dNTPs) and has been associated with cancer progression and cancer cell stemness. We have identified a series of piperazin-1-ylpyridazines as a new class of potent dCTPase inhibitors. Lead compounds increase dCTPase thermal and protease stability, display outstanding selectivity over related enzymes and synergize with a cytidine analogue against leukemic cells. This new class of dCTPase inhibitors lays the first stone toward the development of drug-like probes for the dCTPase enzyme.

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Feb 2, 2017·Journal of Medicinal Chemistry·Sabin Llona-MinguezThomas Helleday

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Citations

Dec 19, 2017·Acta Crystallographica. Section E, Crystallographic Communications·Sergey N Britvin, Andrey M Rumyantsev
Aug 16, 2018·MedChemComm·Sabin Llona-MinguezThomas Helleday
Aug 5, 2019·Cellular and Molecular Life Sciences : CMLS·Blanca Martínez-ArribasDolores González-Pacanowska
Nov 5, 2020·Natural Product Reports·Lu TongJun O Liu
Jan 19, 2020·Journal of Molecular Biology·Emma ScalettiPål Stenmark
Jul 27, 2018·Journal of the American Chemical Society·Samantha A GreenRyan A Shenvi

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