Inhibitors | Comment | Organism | Structure |
---|---|---|---|
(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid | 32.8% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3,7-bis(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 41.0% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 36.6% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 32.3% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 12.8% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 42.4% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 31.8% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-(4-hydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 34.6% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-phenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid | 6.6% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-phenyl-2-oxoquinoxalin-1(2H)-yl)acetic acid | 25.4% inhibition at 0.010 mM | Rattus norvegicus | |
2-(3-thiophenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid | 32.2% inhibition at 0.010 mM | Rattus norvegicus | |
2-(6-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 38.1% inhibition at 0.010 mM | Rattus norvegicus | |
2-(6-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 8.7% inhibition at 0.010 mM | Rattus norvegicus | |
2-(6-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 46.5% inhibition at 0.010 mM | Rattus norvegicus | |
2-(6-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 42.5% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-(4-fluorobenzyl)-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 11.6% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 35.9% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-bromo-3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 17.5% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 24.0% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-bromo-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 10.2% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 44.5% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-chloro-3-(2-benzothiophene)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 53.3% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-chloro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 14.1% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-chloro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 17.3% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-chloro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 23.6% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 46.2% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-fluoro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 45.5% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-fluoro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid | 29.5% inhibition at 0.010 mM | Rattus norvegicus | |
2-(7-fluoro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid | 35.8% inhibition at 0.010 mM | Rattus norvegicus | |
epalrestat | 73.6% inhibition at 0.010 mM | Rattus norvegicus | |
additional information | design and synthesis of inhibitors based on quinoxalinones, overview. Phenolic structure is installed in the compounds for the combination of antioxidant activity and strengthening the ability to fight against diabetic complications, radical scavenging activity using the model reaction with the stable free radicals of 2,2-diphenyl-1-picrylhydrazyl | Rattus norvegicus | |
[2-oxo-3-(2-phenylethyl)quinoxalin-1(2H)-yl]acetic acid | 22.0% inhibition at 0.010 mM | Rattus norvegicus | |
[2-oxo-3-[(Z)-2-phenylethenyl]quinoxalin-1(2H)-yl]acetic acid | 32.0% inhibition at 0.010 mM | Rattus norvegicus | |
[3-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid | 32.6% inhibition at 0.010 mM | Rattus norvegicus | |
[3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid | 42.4% inhibition at 0.010 mM | Rattus norvegicus | |
[3-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid | 21.8% inhibition at 0.010 mM | Rattus norvegicus | |
[3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid | 12.2% inhibition at 0.010 mM | Rattus norvegicus | |
[7-fluoro-3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid | 36.2% inhibition at 0.010 mM | Rattus norvegicus | |
[7-fluoro-3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid | 23.0% inhibition at 0.010 mM | Rattus norvegicus |
Natural Substrates | Organism | Comment (Nat. Sub.) | Natural Products | Comment (Nat. Pro.) | Rev. | Reac. |
---|---|---|---|---|---|---|
D-glucose + NADPH + H+ | Rattus norvegicus | - |
sorbitol + NADP+ | - |
? | |
D-glucose + NADPH + H+ | Rattus norvegicus Wistar | - |
sorbitol + NADP+ | - |
? |
Organism | UniProt | Comment | Textmining |
---|---|---|---|
Rattus norvegicus | P51635 | - |
- |
Rattus norvegicus Wistar | P51635 | - |
- |
Substrates | Comment Substrates | Organism | Products | Comment (Products) | Rev. | Reac. |
---|---|---|---|---|---|---|
D-glucose + NADPH + H+ | - |
Rattus norvegicus | sorbitol + NADP+ | - |
? | |
D-glucose + NADPH + H+ | - |
Rattus norvegicus Wistar | sorbitol + NADP+ | - |
? | |
DL-glyceraldehyde + NADPH + H+ | - |
Rattus norvegicus | ? + NADP+ | - |
? | |
DL-glyceraldehyde + NADPH + H+ | - |
Rattus norvegicus Wistar | ? + NADP+ | - |
? |
Synonyms | Comment | Organism |
---|---|---|
AKR1A1 | - |
Rattus norvegicus |
aldose reductase | - |
Rattus norvegicus |
ALR1 | - |
Rattus norvegicus |
Temperature Optimum [°C] | Temperature Optimum Maximum [°C] | Comment | Organism |
---|---|---|---|
37 | - |
assay at | Rattus norvegicus |
pH Optimum Minimum | pH Optimum Maximum | Comment | Organism |
---|---|---|---|
7.2 | - |
assay at | Rattus norvegicus |
Cofactor | Comment | Organism | Structure |
---|---|---|---|
NADPH | - |
Rattus norvegicus |
General Information | Comment | Organism |
---|---|---|
metabolism | ALR2 is the first rate-determining enzyme in the polyol pathway and catalyzes the reduction of glucose to sorbitol in the presence of NADPH as a cofactor. Sorbitol is in turn converted into fructose with accompanied reduction of NAD+ by sorbitol dehydrogenase. Under normal circumstances, glucose is predominantly converted to glucose-6-phosphate by hexokinase and then enters the glycolytic pathway, whereas only a small amount of glucose is metabolized through the polyol pathway due to a relatively low affinity of ALR2 for this substrate. During hyperglycemia, the polyol metabolic pathway is activated and the increased flux of glucose through the polyol pathway triggers the accumulation of sorbitol, which mainly happens in tissues demonstrating insulin-independent uptake of glucose, such as lens, kidney, retina, and peripheral nerves | Rattus norvegicus |