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Discovery of the First Potent and Selective Inhibitors of Human dCTP Pyrophosphatase 1.

Autori

Llona-Minguez S, Hoglund A, Jacques SA, Johansson L, Calderon-Montano JM, Claesson M, Loseva O, Valerie NC, Lundback T, Piedrafita J, Maga G, Crespan E, Meijer L, Burgos Moron E, Baranczewski P, Hagbjork AL, Svensson R, Wiita E, Almlof I, Visnes T, Jeppsson F, Sigmundsson K, Jensen AJ, Artursson P, Jemth AS, Stenmark P, Warpman Berglund U, Scobie M, Helleday T.

Riferimenti

JOURNAL OF MEDICINAL CHEMISTRY 59(3) 1140-1148, 2016

Autori CNR

MAGA, CRESPAN

Moduli

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.

Link all articolo

http://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.5b01741

Parole Chiave

Note

10.1021/acs.jmedchem.5b01741

Indietro


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