| Literature DB >> 26771665 |
Sabin Llona-Minguez1, Andreas Höglund1, Sylvain A Jacques1, Lars Johansson1,2, José Manuel Calderón-Montaño1, Magnus Claesson3, Olga Loseva1, Nicholas C K Valerie1, Thomas Lundbäck1,2, Javier Piedrafita4, Giovanni Maga5, Emmanuele Crespan5, Laurent Meijer6, Estefanía Burgos Morón1, Pawel Baranczewski1,7, Ann-Louise Hagbjörk7, Richard Svensson7, Elisee Wiita1, Ingrid Almlöf1, Torkild Visnes1, Fredrik Jeppsson1, Kristmundur Sigmundsson1,2, Annika Jenmalm Jensen1,2, Per Artursson7, Ann-Sofie Jemth1, Pål Stenmark3, Ulrika Warpman Berglund1, Martin Scobie1, Thomas Helleday1.
Abstract
The dCTPase pyrophosphatase 1 (dCTPase) regulates the intracellular nucleotide pool through hydrolytic degradation of canonical and noncanonical nucleotide triphosphates (dNTPs). dCTPase is highly expressed in multiple carcinomas and is associated with cancer cell stemness. Here we report on the development of the first potent and selective dCTPase inhibitors that enhance the cytotoxic effect of cytidine analogues in leukemia cells. Boronate 30 displays a promising in vitro ADME profile, including plasma and mouse microsomal half-lives, aqueous solubility, cell permeability and CYP inhibition, deeming it a suitable compound for in vivo studies.Entities:
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Year: 2016 PMID： 26771665 PMCID： PMC4753678 DOI： 10.1021/acs.jmedchem.5b01741
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446