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Novel nonsubstrate inhibitors of human thymidine phosphorylase, a potential target for tumor-dependent angiogenesis.

Abstract：

:Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TP/PD-ECGF) is an enzyme involved in thymidine metabolism and homeostasis, and its catalytic activity appears to play an important role in angiogenesis. Here we describe the cloning and expression of a His-tagged human TP/PD-ECGF and its assay with uracil and thymine analogues. We present the design, synthesis, and biological evaluation of novel 6-(phenylalkylamino)uracil derivatives which, at micromolar concentrations, inhibit both catabolic and anabolic reactions of human TP in vitro. These base analogues are not converted by the enzyme into the nucleoside form, thus representing pure nonsubstrate inhibitors of the enzyme.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Focher F,Ubiali D,Pregnolato M,Zhi C,Gambino J,Wright GE,Spadari S

doi

10.1021/jm000037u

keywords:

subject

Has Abstract

pub_date

2000-06-29 00:00:00

pages

2601-7

issue

13

eissn

0022-2623

issn

1520-4804

pii

jm000037u

journal_volume

43

pub_type

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