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

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Date
2017
Author
Llona-Minguez, S
H?glund, A
Ghassemian, A
Desroses, M
Calder?n-Monta?o, JM
Burgos Mor?n, E
Valerie, NCK
Wiita, E
Alml?f, I
Koolmeister, T
Mateus, A
Cazares-K?rner, C
Sanjiv, K
Homan, E
Loseva, O
Baranczewski, P
Darabi, M
Mehdizadeh, A
Fayezi, S
Jemth, AS
Warpman Berglund, U
Sigmundsson, K
Lundb?ck, T
Jenmalm Jensen, A
Artursson, P
Scobie, M
Helleday, T
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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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http://dspace.tbzmed.ac.ir:8080/xmlui/handle/123456789/38890
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