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Literature summary for 3.6.1.9 extracted from

  • Lee, S.Y.; Perotti, A.; De Jonghe, S.; Herdewijn, P.; Hanck, T.; Mueller, C.E.
    Thiazolo[3,2-a]benzimidazol-3(2H)-one derivatives structure-activity relationships of selective nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) inhibitors (2016), Bioorg. Med. Chem., 24, 3157-3165 .
    View publication on PubMed
Search for more literature for 3.6.1.9

Application

Application Comment Organism
drug development NPP1 has been proposed as a drug target for the treatment of glioblastoma Homo sapiens

Inhibitors

Inhibitors Comment Organism Structure
(2E)-2-([3-methoxy-4-[(1H-tetrazol-5-yl)methoxy]phenyl]methylidene)[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2E)-2-benzylidene[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2E)-2-[(2-oxo-1,2-dihydroquinolin-3-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2E)-2-[(5-iodofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one moderate to low inhibition Homo sapiens
(2E)-2-[(naphthalen-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2E)-2-[[2,4-bis(4-methylpiperidin-1-yl)-5-nitrophenyl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-benzylidene[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-ethylidene[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(2E)-3-phenylprop-2-en-1-ylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(3-phenoxyphenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(4-chlorophenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(4-iodophenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(4-methylphenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(5-bromofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(5-iodofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one highly selective for NPP1 as compared to other human enzymes, i.e. NPP2, NPP3, NTPDases1-3, TNAP, and eN Homo sapiens
(2Z)-2-[(5-methylfuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(5-nitrofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(5-phenylfuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(furan-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(pyridin-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[(thiophen-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[[3-(benzyloxy)phenyl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[[4-(morpholin-4-yl)phenyl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[[5-(dimethylamino)furan-2-yl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
(2Z)-2-[[5-(phenylsulfanyl)furan-2-yl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one
-
 Homo sapiens
1-amino-4-[4-[(4-anilino-6-chloro-1,3,5-triazin-2-yl)amino]-3-sulfoanilino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid
-
 Homo sapiens
1-[(4-methoxyphenyl)methyl]-1H-benzimidazole
-
 Homo sapiens
3,3'-[(2-chlorophenyl)methylene]bis(4-hydroxy-3,4-dihydro-2H-1-benzopyran-2-one)
-
 Homo sapiens
5'-O-(boranyl[[hydroxy(phosphonomethyl)phosphoryl]oxy]phosphoryl)adenosine
-
 Homo sapiens
5'-O-[([[dibromo(phosphono)methyl](hydroxy)phosphoryl]oxy)(hydroxy)phosphoryl]-N,N-diethyladenosine
-
 Homo sapiens
5,5'-(propane-1,3-diyl)di(1,3,4-oxadiazole-2(3H)-thione)
-
 Homo sapiens
8,8'-[carbonylbis[azanediyl-3,1-phenylenecarbonylazanediyl(4-methyl-3,1-phenylene)carbonylazanediyl]]di(naphthalene-1,3,5-trisulfonic acid)
-
 Homo sapiens
adenosine 5'-alpha,beta-methylene-gamma-thiotriphosphate
-
 Homo sapiens
di-2'-deoxyadenosine 5',5''-P1,P5,alpha,beta-methylene-delta,epsilon-methylene-pentaphosphate-gamma-borano
-
 Homo sapiens
additional information structure-activity relationships of thiazolo[3,2-a]benzimidazol-3(2H)-one derivatives as selective nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) inhibitors. Inhibition mechanism, overview Homo sapiens
N-(3,4-dimethoxyphenyl)-2-[(5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]acetamide
-
 Homo sapiens
N-[2-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide
-
 Homo sapiens
polyoxymetalate PSB-POM141
-
 Homo sapiens

Localization

Localization Comment Organism GeneOntology No. Textmining
extracellular enzyme NPP1 is secreted Homo sapiens
-
-
membrane associated Homo sapiens 16020
-
additional information NPP1 is a membrane-associated or secreted enzyme Homo sapiens
-
-

Metals/Ions

Metals/Ions Comment Organism Structure
Ca2+ required Homo sapiens
Mg2+ required Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens O14638
-
-
Homo sapiens P22413
-
-

Posttranslational Modification

Posttranslational Modification Comment Organism
glycoprotein
-
 Homo sapiens

Source Tissue

Source Tissue Comment Organism Textmining
astrocyte
-
 Homo sapiens
-
brain
-
 Homo sapiens
-
glioblastoma cell
-
 Homo sapiens
-
hepatoma cell
-
 Homo sapiens
-
Huh-7 cell
-
 Homo sapiens
-
additional information upregulated expression of NPP1 has been observed in astrocytic brain cancers Homo sapiens
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
4-nitrophenyl 5'-thymidine monophosphate + H2O
-
 Homo sapiens 4-nitrophenol + 5'-thymidine monophosphate
-
 ?
4-nitrophenyl phosphate + H2O
-
 Homo sapiens 4-nitrophenol + phosphate
-
 ?
AMP + H2O
-
 Homo sapiens adenosine + phosphate
-
 ?
ATP + H2O
-
 Homo sapiens ADP + phosphate
-
 ?
ATP + H2O
-
 Homo sapiens AMP + diphosphate
-
 ?

Synonyms

Synonyms Comment Organism
ecto-nucleotide pyrophosphatase/phosphodiesterase1
-
 Homo sapiens
ecto-nucleotide pyrophosphatase/phosphodiesterase3
-
 Homo sapiens
ENPP1
-
 Homo sapiens
ENPP3
-
 Homo sapiens
NPP1
-
 Homo sapiens
NPP3
-
 Homo sapiens
nucleotide pyrophosphastases/phosphodiesterases1
-
 Homo sapiens
nucleotide pyrophosphastases/phosphodiesterases3
-
 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
9
-
 assay at, substrate ATP Homo sapiens

Ki Value [mM]

Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
0.000005
-
 polyoxymetalate PSB-POM141 versus 4-nitrophenyl 5'-thymidine monophosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.00002
-
 adenosine 5'-alpha,beta-methylene-gamma-thiotriphosphate versus 4-nitrophenyl 5'-thymidine monophosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.000059
-
 N-[2-[1-(6,7-dimethoxyquinazolin-4-yl)piperidin-4-yl]ethyl]sulfuric diamide versus 4-nitrophenyl 5'-thymidine monophosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.00026
-
 8,8'-[carbonylbis[azanediyl-3,1-phenylenecarbonylazanediyl(4-methyl-3,1-phenylene)carbonylazanediyl]]di(naphthalene-1,3,5-trisulfonic acid) versus ATP, pH 9.0, 37°C, NPP1 Homo sapiens
0.000467
-
 (2Z)-2-[(5-iodofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.0005
-
 5'-O-(boranyl[[hydroxy(phosphonomethyl)phosphoryl]oxy]phosphoryl)adenosine versus 4-nitrophenyl 5'-thymidine monophosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.00052
-
 1-amino-4-[4-[(4-anilino-6-chloro-1,3,5-triazin-2-yl)amino]-3-sulfoanilino]-9,10-dioxo-9,10-dihydroanthracene-2-sulfonic acid versus ATP, pH 9.0, 37°C, NPP1 Homo sapiens
0.00061
-
 (2Z)-2-[(5-bromofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.000981
-
 (2Z)-2-[(furan-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.00107
-
 (2Z)-2-[(5-nitrofuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.00211
-
 (2Z)-2-[(5-methylfuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.00421
-
 (2Z)-2-[[5-(dimethylamino)furan-2-yl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.00534
-
 N-(3,4-dimethoxyphenyl)-2-[(5-methoxy-3H-imidazo[4,5-b]pyridin-2-yl)sulfanyl]acetamide versus ATP, pH 9.0, 37°C, NPP1 Homo sapiens
0.00856
-
 (2E)-2-[[2,4-bis(4-methylpiperidin-1-yl)-5-nitrophenyl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.00891
-
 (2Z)-2-[[4-(morpholin-4-yl)phenyl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one pH 9.0, 37°C, NPP1 Homo sapiens
0.009
-
 di-2'-deoxyadenosine 5',5''-P1,P5,alpha,beta-methylene-delta,epsilon-methylene-pentaphosphate-gamma-borano versus 4-nitrophenyl 5'-thymidine monophosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2E)-2-([3-methoxy-4-[(1H-tetrazol-5-yl)methoxy]phenyl]methylidene)[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2E)-2-benzylidene[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2E)-2-[(2-oxo-1,2-dihydroquinolin-3-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2E)-2-[(naphthalen-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-benzylidene[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-ethylidene[1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(2E)-3-phenylprop-2-en-1-ylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(3-phenoxyphenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(4-chlorophenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(4-iodophenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(4-methylphenyl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(5-phenylfuran-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(pyridin-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[(thiophen-2-yl)methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[[3-(benzyloxy)phenyl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 (2Z)-2-[[5-(phenylsulfanyl)furan-2-yl]methylidene][1,3]thiazolo[3,2-a]benzimidazol-3(2H)-one above, pH 9.0, 37°C, NPP1 Homo sapiens
0.01
-
 1-[(4-methoxyphenyl)methyl]-1H-benzimidazole above, pH 9.0, 37°C, NPP1 Homo sapiens
0.012
-
 5'-O-[([[dibromo(phosphono)methyl](hydroxy)phosphoryl]oxy)(hydroxy)phosphoryl]-N,N-diethyladenosine versus 4-nitrophenyl 5'-thymidine monophosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.05
-
 3,3'-[(2-chlorophenyl)methylene]bis(4-hydroxy-3,4-dihydro-2H-1-benzopyran-2-one) versus p-nitrophenyl phenyl phosphate, pH 9.0, 37°C, NPP1 Homo sapiens
0.15
-
 5,5'-(propane-1,3-diyl)di(1,3,4-oxadiazole-2(3H)-thione) versus p-nitrophenyl phenyl phosphate, pH 9.0, 37°C, NPP1 Homo sapiens

Expression

Organism Comment Expression
Homo sapiens upregulated expression of NPP1 has been observed in astrocytic brain cancers up

General Information

General Information Comment Organism
evolution ecto-nucleotide pyrophosphatase/phosphodiesterase1 (NPP1) is the most important member of the NPP family, which consists of seven closely related proteins (NPP1-NPP7) Homo sapiens
evolution ecto-nucleotide pyrophosphatase/phosphodiesterase3 (NPP3) belongs to the NPP family, which consists of seven closely related proteins (NPP1-NPP7) Homo sapiens
malfunction role for NPP1 in insulin receptor signaling: overexpression of NPP1 increases insulin resistance by desensitization of the insulin receptor. Knockdown of NPP1 with siRNA significantly increases insulin-stimulated phosphorylation of tyrosine kinase in a human hepatoma cell line (HUH7) Homo sapiens
physiological function enzyme NPP1 catalyzes the hydrolysis of a wide range of phosphodiester bonds, e.g. in nucleoside triphosphates, dinucleotides and nucleotide sugars. NPP1 plays a crucial role in various physiological functions including bone mineralization, soft-tissue calcification, and insulin receptor signaling Homo sapiens