Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.1.4.1 (
phosphodiesterase
)
18,767
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Nucleotide pyrophosphatase/
phosphodiesterase
type 1 (NPP1) is a membrane glycoprotein involved in the hydrolysis of extracellular nucleotides. Its major substrate is ATP which is converted to AMP and diphosphate. NPP1 was proposed as a new therapeutic target in
brain cancer
and immuno-oncology. Several NPP1 inhibitors have been reported to date, most of which were evaluated vs. the artificial substrate
p
-nitrophenyl 5'-thymidine monophosphate (
p
-Nph-5'-TMP). Recently, we observed large discrepancies in inhibitory potencies for a class of competitive NPP1 inhibitors when tested vs. the artificial substrate
p
-Nph-5'-TMP as compared to the natural substrate ATP. Therefore, the goal of the present study was to investigate whether inhibitors of human NPP1 generally display substrate-dependent inhibitory potency. Systematic evaluation of nucleotidic as well as non-nucleotidic NPP1 inhibitors revealed significant differences in determined
K
i
values for competitive, but not for non- and un-competitive inhibitors when tested vs. the frequently used artificial substrate
p
-Nph-5'-TMP as compared to ATP. Allosteric modulation of NPP1 by
p
-Nph-5'-TMP may explain these discrepancies. Results obtained using the AMP derivative
p
-nitrophenyl 5'-adenosine monophosphate (
p
-Nph-5'-AMP) as an alternative artificial substrate correlated much better with those employing the natural substrate ATP.
...
PMID:Substrate-Dependence of Competitive Nucleotide Pyrophosphatase/Phosphodiesterase1 (NPP1) Inhibitors. 2826 Oct 95
