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Literature summary for 3.1.4.1 extracted from

  • Nadel, Y.; Lecka, J.; Gilad, Y.; Ben-David, G.; Foerster, D.; Reiser, G.; Kenigsberg, S.; Camden, J.; Weisman, G.A.; Senderowitz, H.; Sevigny, J.; Fischer, B.
    Highly potent and selective ectonucleotide pyrophosphatase/phosphodiesterase I inhibitors based on an adenosine 5-(alpha or gamma)-thio-(alpha,beta- or beta,gamma)-methylenetriphosphate scaffold (2014), J. Med. Chem., 57, 4677-4691.
    View publication on PubMedView publication on EuropePMC
Search for more literature for 3.1.4.1

Inhibitors

Inhibitors Comment Organism Structure
(RP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
 Homo sapiens
(RP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
 Homo sapiens
(SP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
-
 Homo sapiens
(SP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
-
 Homo sapiens
8-thioadenosine 5'-triphosphate
-
 Homo sapiens
adenosine 5'-(gamma-thio-beta,gamma-methylene)triphosphate
-
 Homo sapiens
AMP product inhibition of NPP1 Homo sapiens
additional information design and synthesis of highly potent and selective ectonucleotide pyrophosphatase/phosphodiesterase I inhibitors based on an adenosine 5-(alpha or gamma)-thio-(alpha,beta- or beta,gamma)-methylenetriphosphate scaffold, compound configurations analsis by NMR spectroscopy, overview. Analogue 4 is not a good inhibitor. The thiophosphate groups are designed to chelate the tentative Zn2+ ions. Docking od 1-3 into the NPP1 model suggests that activity correlates with the number of H-bonds with binding site residues, overview Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ activates Homo sapiens
Mg2+ activates Homo sapiens
Zn2+ the catalytic binding site of NPP1 contains two Zn2+ ions Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens
-
-
-

Source Tissue

Source Tissue Comment Organism Textmining
cartilage
-
 Homo sapiens
-
chondrocyte
-
 Homo sapiens
-
osteoblast
-
 Homo sapiens
-
SAOS-2 cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
additional information isozymes NPP1 and NPP3 can hydrolyze ATP, as well as inhibitor molecule 4, they also show very low activity with inhibitors 1 and 2, 1-4% compared to the activit with ATP Homo sapiens ?
-
 ?

Synonyms

Synonyms Comment Organism
NPP1
-
 Homo sapiens
NPP2
-
 Homo sapiens
NPP3
-
 Homo sapiens
nucleotide pyrophosphatase/phosphodiesterase-1
-
 Homo sapiens
nucleotide pyrophosphatase/phosphodiesterase-2
-
 Homo sapiens
nucleotide pyrophosphatase/phosphodiesterase-3
-
 Homo sapiens

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
37
-
 assay at Homo sapiens

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
8.5
-
 assay at Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.00002
-
 adenosine 5'-(gamma-thio-beta,gamma-methylene)triphosphate pH 8.5, 37°C, enzyme NPP1 Homo sapiens
0.000685
-
 (RP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate pH 8.5, 37°C, enzyme NPP1 Homo sapiens
0.0013
-
 (SP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate pH 8.5, 37°C, enzyme NPP1 Homo sapiens
0.0045
-
 (RP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate pH 8.5, 37°C, enzyme NPP1 Homo sapiens
0.0152
-
 (SP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate pH 8.5, 37°C, enzyme NPP1 Homo sapiens

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.00039
-
 pH 8.5, 37°C, enzyme NPP1 Homo sapiens adenosine 5'-(gamma-thio-beta,gamma-methylene)triphosphate
0.0006
-
 pH 8.5, 37°C, enzyme NPP1 Homo sapiens (RP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate
0.0163
-
 pH 8.5, 37°C, enzyme NPP1 Homo sapiens (RP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
0.0187
-
 pH 8.5, 37°C, enzyme NPP1 Homo sapiens (SP)-adenosine 5'-(alpha-thio-beta,gamma-methylene)triphosphate
0.0312
-
 pH 8.5, 37°C, enzyme NPP1 Homo sapiens (SP)-adenosine 5'-(alpha-thio-beta,gamma-dichloromethylene)triphosphate

General Information

General Information Comment Organism
evolution the enzymes belongs to the ectonucleotide pyrophosphatase/phosphodiesterase (NPP) family Homo sapiens
malfunction aberrant nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is associated with chondrocalcinosis, osteoarthritis, and type 2 diabetes Homo sapiens