Any feedback?
Please rate this page
(literature.php)
(0/150)

BRENDA support

Literature summary extracted from

  • Xu, A.; He, F.; Yu, C.; Qu, Y.; Zhang, Q.; Lv, J.; Zhang, X.; Ran, Y.; Wei, C.; Wu, J.
    The development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease (2019), ChemistrySelect, 4, 10591-10600 .
No PubMed abstract available

Application

EC Number Application Comment Organism
2.3.2.5 drug development development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease Homo sapiens

Inhibitors

EC Number Inhibitors Comment Organism Structure
2.3.2.5 1,2-di-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glycopyranosyl)-glycerol
-
 Homo sapiens
2.3.2.5 1-(3,4-dimethoxyphenyl)-N-[3-(1H-imidazol-1-yl)propyl]cyclopropane-1-carbothioamide
-
 Homo sapiens
2.3.2.5 1-O-linolyl-2-O-palmitoyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
 Homo sapiens
2.3.2.5 1-O-palmitoyl-2-O-linolenyl-3-O-(6'-deoxy-6'-sulfo-D-glucopyranosyl)-glycerol
-
 Homo sapiens
2.3.2.5 3-fluoro-3',4'-dimethoxy-N-[3-(4-methyl-1H-imidazol-1-yl)propyl][1,1'-biphenyl]-2-amine
-
 Homo sapiens
2.3.2.5 3-[(1H-imidazol-1-yl)methyl]aniline
-
 Homo sapiens
2.3.2.5 3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-sulfanylidene-2,3,5,6,7,8-hexahydro[1]benzothieno[2,3-d]pyrimidin-4(1H)-one
-
 Homo sapiens
2.3.2.5 3-[3-(5-methyl-1H-imidazol-1-yl)propyl]-2-sulfanylidene-2,3-dihydroquinazolin-4(1H)-one
-
 Homo sapiens
2.3.2.5 3-[4-(1H-imidazol-1-yl)butoxy]benzaldehyde
-
 Homo sapiens
2.3.2.5 4'-fluoro-N-[3-(4-methyl-1H-imidazol-1-yl)propyl][1,1'-biphenyl]-2-amine
-
 Homo sapiens
2.3.2.5 4-[2-(1H-imidazol-1-yl)ethoxy]benzaldehyde
-
 Homo sapiens
2.3.2.5 4-[2-[4-([1-[(3-aminophenyl)methyl]-1H-imidazol-2-yl]methyl)-1H-imidazol-1-yl]ethoxy]benzaldehyde
-
 Homo sapiens
2.3.2.5 5,7-dihydroxy-2-(3-methylphenyl)-4H-1-benzopyran-4-one
-
 Homo sapiens
2.3.2.5 5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
 Homo sapiens
2.3.2.5 5-(5-[[(pyridin-4-yl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
-
 Homo sapiens
2.3.2.5 5-[5-(2-phenylethyl)-1,3,4-oxadiazol-2-yl]-1H-benzimidazole
-
 Homo sapiens
2.3.2.5 apigenin
-
 Homo sapiens
2.3.2.5 cysteamine
-
 Homo sapiens
2.3.2.5 additional information development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease, overview; development of small molecule inhibitors of glutaminyl cyclase and isoglutaminyl cyclase for Alzheimers disease, overview. Weak inhibition by imidazole derivatives Homo sapiens
2.3.2.5 N''-cyano-N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]guanidine
-
 Homo sapiens
2.3.2.5 N''-cyano-N-methyl-N'-[3-(4-methyl-1H-imidazol-1-yl)propyl]guanidine
-
 Homo sapiens
2.3.2.5 N''-cyano-N-methyl-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]guanidine
-
 Homo sapiens
2.3.2.5 N-(2,3-dihydro-1,4-benzodioxin-6-yl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
 Homo sapiens
2.3.2.5 N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)-2-methylpropyl]thiourea
-
 Homo sapiens
2.3.2.5 N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea
-
 Homo sapiens
2.3.2.5 N-(3,4-dimethoxyphenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
 Homo sapiens
2.3.2.5 N-(3-methoxy-4-[[4-(piperidin-4-yl)phenyl]methoxy]phenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
-
 Homo sapiens
2.3.2.5 N-(4-chlorophenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea
-
 Homo sapiens
2.3.2.5 N-[3-(4-aminobutoxy)-4-methoxyphenyl]-N'-[3-(2-methyl-1H-imidazol-1-yl)propyl]thiourea
-
 Homo sapiens
2.3.2.5 PBD150
-
 Homo sapiens
2.3.2.5 PQ912
-
 Homo sapiens

Localization

EC Number Localization Comment Organism GeneOntology No. Textmining
2.3.2.5 extracellular the isozyme is secreted Homo sapiens
-
-
2.3.2.5 Golgi membrane
-
 Homo sapiens 139
-

Metals/Ions

EC Number Metals/Ions Comment Organism Structure
2.3.2.5 Zn2+ required Homo sapiens

Natural Substrates/ Products (Substrates)

EC Number Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
2.3.2.5 L-glutaminyl-Abeta3-40/42 Homo sapiens amyloid-beta peptide Abeta3-40/42 5-oxoprolyl-Abeta3-40/42 + NH3
-
 r
2.3.2.5 L-glutaminyl-CCL2 Homo sapiens i.e. monocyte chemoattractant protein (MCP-1) 5-oxoprolyl-CCL2 + NH3
-
 r
2.3.2.5 L-glutaminyl-peptide Homo sapiens
-
 5-oxoprolyl-peptide + NH3
-
 r

Organism

EC Number Organism UniProt Comment Textmining
2.3.2.5 Homo sapiens Q16769
-
-
2.3.2.5 Homo sapiens Q9NXS2
-
-

Source Tissue

EC Number Source Tissue Comment Organism Textmining
2.3.2.5 Hep-G2 cell
-
 Homo sapiens
-
2.3.2.5 hepatoma cell
-
 Homo sapiens
-

Substrates and Products (Substrate)

EC Number Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
2.3.2.5 L-glutaminyl-Abeta3-40/42 amyloid-beta peptide Abeta3-40/42 Homo sapiens 5-oxoprolyl-Abeta3-40/42 + NH3
-
 r
2.3.2.5 L-glutaminyl-CCL2 i.e. monocyte chemoattractant protein (MCP-1) Homo sapiens 5-oxoprolyl-CCL2 + NH3
-
 r
2.3.2.5 L-glutaminyl-CCL2 i.e. monocyte chemoattractant protein (MCP-1), CCL2 is a specific substrate for h-isoQC but not for h-QC Homo sapiens 5-oxoprolyl-CCL2 + NH3
-
 r
2.3.2.5 L-glutaminyl-peptide
-
 Homo sapiens 5-oxoprolyl-peptide + NH3
-
 r
2.3.2.5 L-glutaminyl-Phe-Ala
-
 Homo sapiens 5-oxoprolyl-Phe-Ala + NH3
-
 r
2.3.2.5 additional information cyclization reaction of glutamate and glutamine residues, overview Homo sapiens ?
-
-
2.3.2.5 additional information cyclization reaction of glutamate and glutamine residues, overview. CCL2 is a specific substrate for h-isoQC but not for h-QC Homo sapiens ?
-
-

Synonyms

EC Number Synonyms Comment Organism
2.3.2.5 glutaminyl cyclase
-
 Homo sapiens
2.3.2.5 golgi resident enzyme
-
 Homo sapiens
2.3.2.5 gQC
-
 Homo sapiens
2.3.2.5 h-isoQC
-
 Homo sapiens
2.3.2.5 h-QC
-
 Homo sapiens
2.3.2.5 isoGlutaminyl cyclase
-
 Homo sapiens
2.3.2.5 secretory glutaminyl cyclase
-
 Homo sapiens
2.3.2.5 sQC
-
 Homo sapiens

Ki Value [mM]

EC Number Ki Value [mM] Ki Value maximum [mM] Inhibitor Comment Organism Structure
2.3.2.5 0.000006
-
 N-(3,4-dimethoxyphenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea pH and temperature not specified in the publication Homo sapiens
2.3.2.5 0.000023
-
 5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole pH and temperature not specified in the publication Homo sapiens
2.3.2.5 0.000638
-
 5-[5-(2-phenylethyl)-1,3,4-oxadiazol-2-yl]-1H-benzimidazole pH and temperature not specified in the publication Homo sapiens
2.3.2.5 0.00101
-
 5-(5-[[(pyridin-4-yl)methyl]sulfanyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole pH and temperature not specified in the publication Homo sapiens
2.3.2.5 0.00124
-
 N-(4-chlorophenyl)-N'-[3-(1H-imidazol-1-yl)propyl]thiourea pH and temperature not specified in the publication Homo sapiens

IC50 Value

EC Number IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
2.3.2.5 0.0000062
-
 pH and temperature not specified in the publication Homo sapiens N-(3-methoxy-4-[[4-(piperidin-4-yl)phenyl]methoxy]phenyl)-N'-[3-(5-methyl-1H-imidazol-1-yl)propyl]thiourea
2.3.2.5 0.0000088
-
 pH and temperature not specified in the publication Homo sapiens N-[3-(4-aminobutoxy)-4-methoxyphenyl]-N'-[3-(2-methyl-1H-imidazol-1-yl)propyl]thiourea
2.3.2.5 0.00007
-
 pH and temperature not specified in the publication Homo sapiens 5-(5-[[(3,4-dimethoxyphenyl)sulfanyl]methyl]-1,3,4-oxadiazol-2-yl)-1H-benzimidazole
2.3.2.5 0.00396
-
 pH and temperature not specified in the publication Homo sapiens 5-[5-(2-phenylethyl)-1,3,4-oxadiazol-2-yl]-1H-benzimidazole

General Information

EC Number General Information Comment Organism
2.3.2.5 evolution glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) belong to the family of the metalloenzymes Homo sapiens
2.3.2.5 malfunction loss of the pE-modification and N-terminal charge leads to accelerated aggregation of Abeta3(pE) compared with unmodified Abeta Homo sapiens
2.3.2.5 physiological function glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) catalyze the intramolecular cyclization of N-terminal L-glutamine/glutamate residues of certain proteins into diglutamic acid (pGlu). The amyloid protein and the monocyte chemoattractant protein (MCP-1) also known as CCL2 that promotes a cascade of inflammation-related responses are two representative substrates. The diglutamated Abeta and CCL2 exhibit more severe neurotoxicity than normal Abeta and CCL2. The Abeta1-40/42 peptides start with an L-aspartate at the N-terminus. Under pathological conditions, the Abeta1-40/42 peptides are truncated to expose the glutamate at position 3 or 11 of the Abeta peptides. Then the N-terminal glutamate (E) will be cyclized by QC to form the pyroglutamate (pE) and the products are termed as Abeta3(pE)-40/42 or Abeta11(pE)-40/42. The pE-modification of Abeta confers unique properties, such as proteolytic resistance. pGlu-Abeta peptides exhibit enhanced toxicity compared to the unmodified Abeta peptide and promote the formation of tau tangles. In Alzheimer's disease (AD) patients and animal AD models, the level and activity of QC are significantly increased Homo sapiens
2.3.2.5 physiological function glutaminyl cyclase (QC) and isoglutaminyl cyclase (isoQC) catalyze the intramolecular cyclization of N-terminal L-glutamine/glutamate residues of certain proteins into diglutamic acid (pGlu). The level of CCL2 and h-isoQCmRNA in Alzheimer disease (AD) patients is significantly higher than that of healthy subjects Homo sapiens