Literature summary for 2.3.2.5 extracted from

Li, M.; Dong, Y.; Yu, X.; Zou, Y.; Zheng, Y.; Bu, X.; Quan, J.; He, Z.; Wu, H.
Inhibitory effect of flavonoids on human glutaminyl cyclase (2016), Bioorg. Med. Chem., 24, 2280-2286 .

Application

Application	Comment	Organism
drug development	the enzyme is a potential target for the development of novel anti-Alzheimer disease agents. Phenol-40 (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives are synthesized and evaluated as another class of human QC (hQC) inhibitors	Homo sapiens

Inhibitors

Inhibitors	Comment	Organism
2-(2,3-dimethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	87.7% inhibition at 0.1 mM	Homo sapiens
2-(2,3-dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one	54.3% inhibition at 0.1 mM	Homo sapiens
2-(2,4-dimethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	71.7% inhibition at 0.1 mM	Homo sapiens
2-(2-fluorophenyl)-5,7-dihydroxy-4H-chromen-4-one	84.2% inhibition at 0.1 mM	Homo sapiens
2-(2-fluorophenyl)-7-hydroxy-4H-chromen-4-one	60.8% inhibition at 0.1 mM	Homo sapiens
2-(3,4-dimethoxyphenyl)-7-hydroxy-4H-chromen-4-one	68.3% inhibition at 0.1 mM	Homo sapiens
2-(3-fluorophenyl)-7-hydroxy-4H-chromen-4-one	63.3% inhibition at 0.1 mM	Homo sapiens
2-(4-(dimethylamino)phenyl)-7-hydroxy-4H-chromen-4-one	90.3% inhibition at 0.1 mM	Homo sapiens
2-(4-ethoxyphenyl)-5,7-dihydroxy-4H-chromen-4-one	91.5% inhibition at 0.1 mM	Homo sapiens
2-(4-ethoxyphenyl)-7-hydroxy-4H-chromen-4-one	67.6% inhibition at 0.1 mM	Homo sapiens
2-(4-ethylphenyl)-5,7-dihydroxy-4H-chromen-4-one	85.2% inhibition at 0.1 mM	Homo sapiens
2-(4-ethylphenyl)-7-hydroxy-4H-chromen-4-one	79.5% inhibition at 0.1 mM	Homo sapiens
2-(4-fluorophenyl)-7-hydroxy-4H-chromen-4-one	74.2% inhibition at 0.1 mM	Homo sapiens
2-(furan-2-yl)-7-hydroxy-4H-chromen-4-one	68.7% inhibition at 0.1 mM	Homo sapiens
2-(furan-3-yl)-7-hydroxy-4H-chromen-4-one	61.4% inhibition at 0.1 mM	Homo sapiens
5,7-dihydroxy-2-(3-methylthiophen-2-yl)-4H-chromen-4-one	91.6% inhibition at 0.1 mM	Homo sapiens
5,7-dihydroxy-2-(5-methylthiophen-2-yl)-4H-chromen-4-one	92.4% inhibition at 0.1 mM	Homo sapiens
5,7-dihydroxy-2-(m-tolyl)-4H-chromen-4-one	93.0% inhibition at 0.1 mM	Homo sapiens
5,7-dihydroxy-2-(thiophen-2-yl)-4H-chromen-4-one	92.6% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(2-(trifluoromethyl)phenyl)-4H-chromen-4-one	70.8% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(2-methoxyphenyl)-4H-chromen-4-one	54.5% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one	68.7% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(4-(methylthio)phenyl)-4H-chromen-4-one	75.8% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-4-one	71.8% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(4-methoxyphenyl)-4H-chromen-4-one	75.2% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(5-methylfuran-2-yl)-4H-chromen-4-one	78.9% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(pyridin-2-yl)-4H-chromen-4-one	62.4% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(pyridin-3-yl)-4H-chromen-4-one	65.2% inhibition at 0.1 mM	Homo sapiens
7-hydroxy-2-(pyridin-4-yl)-4H-chromen-4-one	87.1% inhibition at 0.1 mM	Homo sapiens
apigenin	75.2% inhibition at 0.1 mM	Homo sapiens
additional information	phenol-40 (R1-), C5-OH (R2-) and C7-OH (R3-) modified apigenin derivatives are synthesized and evaluated as human QC (hQC) inhibitors, structure-function analysis, molecular docking, overview. No inhibition by 7-methoxy-2-(3-methylthiophen-2-yl)-4H-chromen-4-one, 7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one, 7-methoxy-2-(2-methoxyphenyl)-4H-chromen-4-one, 2-(3,4-dimethoxyphenyl)-7-methoxy-4H-chromen-4-one, 7-methoxy-2-(3,4,5-trimethoxyphenyl)-4H-chromen-4-one, 2-(4-fluorophenyl)-7-methoxy-4H-chromen-4-one, 2-(3-fluorophenyl)-7-methoxy-4H-chromen-4-one, 7-methoxy-2-(2-(trifluoromethyl)phenyl)-4H-chromen-4-one, 7-methoxy-2-(pyridin-3-yl)-4H-chromen-4-one, 2-(furan-2-yl)-7-methoxy-4H-chromen-4-one, and 2-(furan-3-yl)-7-methoxy-4H-chromen-4-one	Homo sapiens
PBD150	-	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
L-glutaminyl-peptide	Homo sapiens	-	5-oxoprolyl-peptide + NH3	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	Q16769	isozyme sQC	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
brain	-	Homo sapiens	-
cerebral cortex	-	Homo sapiens	-
hippocampus	-	Homo sapiens	-
additional information	enzyme QC is abundant in mammalian secretory tissue such as secretory glands or brain tissue including hippocampus and cortex	Homo sapiens	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
L-glutaminyl-peptide	-	Homo sapiens	5-oxoprolyl-peptide + NH3	-	?

Synonyms

Synonyms	Comment	Organism
glutaminyl cyclase	-	Homo sapiens
hQC	-	Homo sapiens

IC50 Value

IC50 Value	IC50 Value Maximum	Comment	Organism	Inhibitor	Structure
0.0053	-	pH and temperature not specified in the publication	Homo sapiens	PBD150

General Information

General Information	Comment	Organism
physiological function	glutaminyl cyclase (QC) is one kind of acyltransferases, which catalyzes intramolecular cyclization of N-terminal glutamine residues to diglutamic acid (pGlu) with the concomitant liberation of ammonia. The post-translational formation of pGlu is an important process for the maturation of various bioactive neuropeptides, hormones, cytokines and for their biological activity, because the pGlu is required to protect the N termini from exopeptidase degradation and/or to develop the proper conformation. QC is abundant in mammalian secretory tissue such as secretory glands or brain tissue including hippocampus and cortex. Glutaminyl cyclase (QC) plays an important role in the initiation of the formation of neurotoxic plaques and in the pathogenesis of Alzheimer's disease (AD) due to the ability of human QC (hQC) to convert the N-terminal glutamate of beta-amyloids (Abetas) into respective pGlu-modified Abetas (pE-Abetas)	Homo sapiens