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Literature summary for 1.1.1.21 extracted from

  • Qin, X.; Hao, X.; Han, H.; Zhu, S.; Yang, Y.; Wu, B.; Hussain, S.; Parveen, S.; Jing, C.; Ma, B.; Zhu, C.
    Design and synthesis of potent and multifunctional aldose reductase inhibitors based on quinoxalinones (2015), J. Med. Chem., 58, 1254-1267.
    View publication on PubMed

Inhibitors

Inhibitors Comment Organism Structure
(3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
1,2-benzothiazin-1,1-dioxide
-
Rattus norvegicus
2-(3,7-bis(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-(4-hydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-phenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-phenyl-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(3-thiophenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(6-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(6-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(6-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(6-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-(4-fluorobenzyl)-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(7-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-bromo-3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(7-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-bromo-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-chloro-3-(2-benzothiophene)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-chloro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-chloro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-chloro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
2-(7-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-fluoro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-fluoro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
-
Rattus norvegicus
2-(7-fluoro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
-
Rattus norvegicus
6-(5-chloro,3-methylbenzofuran-2-sulfonyl)2H-pyridazin-3-one
-
Rattus norvegicus
epalrestat
-
Rattus norvegicus
fidarestat
-
Rattus norvegicus
lidorestat
-
Rattus norvegicus
additional information design and synthesis of potent and multifunctional aldose reductase 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. Molecular docking study using the lidorestat-bound conformation of ALR2, PDB ID 1Z3N Rattus norvegicus
ponalrestat
-
Rattus norvegicus
sorbinil
-
Rattus norvegicus
zenorestat
-
Rattus norvegicus
[2-oxo-3-(2-phenylethyl)quinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[2-oxo-3-[(Z)-2-phenylethenyl]quinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[3-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[3-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[7-fluoro-3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus
[7-fluoro-3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
-
Rattus norvegicus

Natural Substrates/ Products (Substrates)

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

Organism UniProt Comment Textmining
Rattus norvegicus P07943
-
-
Rattus norvegicus Wistar P07943
-
-

Substrates and Products (Substrate)

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 glycerol + NADP+
-
?
DL-glyceraldehyde + NADPH + H+
-
Rattus norvegicus Wistar glycerol + NADP+
-
?

Synonyms

Synonyms Comment Organism
AKR1B1
-
Rattus norvegicus
aldose reductase
-
Rattus norvegicus
ALR2
-
Rattus norvegicus

Temperature Optimum [°C]

Temperature Optimum [°C] Temperature Optimum Maximum [°C] Comment Organism
30
-
assay at Rattus norvegicus

pH Optimum

pH Optimum Minimum pH Optimum Maximum Comment Organism
6.2
-
assay at Rattus norvegicus

Cofactor

Cofactor Comment Organism Structure
NADPH
-
Rattus norvegicus

IC50 Value

IC50 Value IC50 Value Maximum Comment Organism Inhibitor Structure
0.000032
-
pH 6.2, 30°C Rattus norvegicus 2-(7-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000056
-
pH 6.2, 30°C Rattus norvegicus 2-(7-fluoro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.00006
-
pH 6.2, 30°C Rattus norvegicus 2-(6-fluoro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000069
-
pH 6.2, 30°C Rattus norvegicus 2-(7-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000084
-
pH 6.2, 30°C Rattus norvegicus epalrestat
0.000091
-
pH 6.2, 30°C Rattus norvegicus 2-(7-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000095
-
pH 6.2, 30°C Rattus norvegicus 2-(6-chloro-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000139
-
pH 6.2, 30°C Rattus norvegicus 2-(6-bromo-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.00014
-
pH 6.2, 30°C Rattus norvegicus [2-oxo-3-(2-phenylethyl)quinoxalin-1(2H)-yl]acetic acid
0.000153
-
pH 6.2, 30°C Rattus norvegicus [7-fluoro-3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
0.000158
-
pH 6.2, 30°C Rattus norvegicus 2-(7-chloro-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.00018
-
pH 6.2, 30°C Rattus norvegicus [3-[(E)-2-(4-hydroxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
0.00019
-
pH 6.2, 30°C Rattus norvegicus 2-(7-fluoro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000238
-
pH 6.2, 30°C Rattus norvegicus 2-(7-chloro-3-(2-benzothiophene)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.00027
-
pH 6.2, 30°C Rattus norvegicus 2-(3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.000296
-
pH 6.2, 30°C Rattus norvegicus 2-(3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.000319
-
pH 6.2, 30°C Rattus norvegicus 2-(6-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000326
-
pH 6.2, 30°C Rattus norvegicus 2-(7-chloro-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000368
-
pH 6.2, 30°C Rattus norvegicus 2-(7-bromo-3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.000395
-
pH 6.2, 30°C Rattus norvegicus 2-(7-bromo-3-(4-chlorothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.0004
-
pH 6.2, 30°C Rattus norvegicus 2-(3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.000419
-
pH 6.2, 30°C Rattus norvegicus [3-[(E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
0.00042
-
pH 6.2, 30°C Rattus norvegicus 2-(3-thiophenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.000467
-
pH 6.2, 30°C Rattus norvegicus 2-(7-bromo-3-(4-bromothiophenoxy)-2-oxoquinoxalin-1(2H)-yl)-acetic acid
0.000468
-
pH 6.2, 30°C Rattus norvegicus 2-(3-phenoxy-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.000639
-
pH 6.2, 30°C Rattus norvegicus 2-(3-(3-indolyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00065
-
pH 6.2, 30°C Rattus norvegicus [7-fluoro-3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
0.0008
-
pH 6.2, 30°C Rattus norvegicus [3-[2-(4-hydroxyphenyl)ethyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
0.00082
-
pH 6.2, 30°C Rattus norvegicus [2-oxo-3-[(Z)-2-phenylethenyl]quinoxalin-1(2H)-yl]acetic acid
0.00087
-
pH 6.2, 30°C Rattus norvegicus 2-(7-fluoro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00111
-
pH 6.2, 30°C Rattus norvegicus (3-benzyl-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00152
-
pH 6.2, 30°C Rattus norvegicus 2-(7-chloro-3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00213
-
pH 6.2, 30°C Rattus norvegicus 2-(3,7-bis(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00334
-
pH 6.2, 30°C Rattus norvegicus 2-(7-(4-fluorobenzyl)-3-(2,4-dihydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00338
-
pH 6.2, 30°C Rattus norvegicus 2-(3-(4-fluorophenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid
0.00418
-
pH 6.2, 30°C Rattus norvegicus [3-[(E)-2-(4-methoxyphenyl)ethenyl]-2-oxoquinoxalin-1(2H)-yl]acetic acid
0.00598
-
pH 6.2, 30°C Rattus norvegicus 2-(3-phenyl-2-oxoquinoxalin-1(2H)-yl)acetic acid
259
-
pH 6.2, 30°C Rattus norvegicus 2-(3-(4-hydroxyphenyl)-2-oxoquinoxalin-1(2H)-yl)acetic acid

General Information

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