Target Information

Target General Infomation
Target ID
T26623
Former ID
TTDS00115
Target Name
Aldose reductase
Gene Name
AKR1B1
Synonyms
AR; Aldehyde reductase; AKR1B1
Target Type
Successful
Disease Diabetic complication [ICD10: E08-E13]
Diabetic cataract [ICD10: E10.36, E11.36]
Diabetic neuropathy [ICD9: 250, 250.6, 356.0, 356.8; ICD10: E11.40]
Diabetes [ICD9: 253.5, 588.1; ICD10: E23.2, N25.1]
Glaucoma [ICD9: 365; ICD10: H40-H42]
Gout [ICD9: 274.00274.1274.8274.9; ICD10: M10]
Head and neck cancer [ICD9: 140-149, 140-229; ICD10: C07-C14, C32-C33]
Rheumatoid arthritis [ICD9: 710-719, 714; ICD10: M05-M06]
Function
Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
BioChemical Class
Short-chain dehydrogenases reductases
Target Validation
T26623
UniProt ID
P15121
EC Number
EC 1.1.1.21
Sequence
MASRLLLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQNENEVGVAIQ
EKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDLKLDYLDLYLIHWPTGFKPGK
EFFPLDESGNVVPSDTNILDTWAAMEELVDEGLVKAIGISNFNHLQVEMILNKPGLKYKP
AVNQIECHPYLTQEKLIQYCQSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAK
HNKTTAQVLIRFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
LLSCTSHKDYPFHEEF
Drugs and Mode of Action
Drug(s) Epalrestat Drug Info Approved Diabetic neuropathy [536361]
Sulindac Drug Info Approved Rheumatoid arthritis [536772], [540828]
Fidarestat Drug Info Phase 3 Diabetes [532182]
Ranirestat Drug Info Phase 3 Diabetic neuropathy [521626]
ADMVA Drug Info Phase 2 Diabetes [521758], [530668]
LIDORESTAT Drug Info Phase 2 Diabetic complication [521528], [542435]
M-16209 Drug Info Phase 2 Diabetes [544516]
QR-333 Drug Info Phase 2 Diabetic neuropathy [522174]
T2c-003 Drug Info Phase 1/2 Diabetic neuropathy [548845]
ALO-1567 Drug Info Phase 1 Glaucoma [530034]
ARI-809 Drug Info Preclinical Diabetes [549081]
Tolrestat Drug Info Withdrawn from market Diabetic cataract [534401], [542427]
IMIRESTAT Drug Info Discontinued in Phase 3 Diabetes [544515]
MINALRESTAT Drug Info Discontinued in Phase 3 Diabetes [545360]
Ponalrestat Drug Info Discontinued in Phase 3 Gout [544513]
AD-5467 Drug Info Discontinued in Phase 2 Diabetes [544842]
Alrestatin Drug Info Discontinued in Phase 2 Discovery agent [545678]
CTL-102-GDEPT Drug Info Discontinued in Phase 2 Head and neck cancer [546958]
JTT-811 Drug Info Discontinued in Phase 2 Diabetic complication [547576]
ZOPOLRESTAT Drug Info Discontinued in Phase 2 Diabetic complication [542443], [544806]
E-0722 Drug Info Terminated Diabetic cataract [545784]
FR-62765 Drug Info Terminated Diabetes [529820]
Sorbinil Drug Info Terminated Diabetic cataract [542439], [544510]
SPR-210 Drug Info Terminated Diabetic complication [545343]
WF-2421 Drug Info Terminated Diabetes [529812]
Zenarestat Drug Info Terminated Diabetic neuropathy [542442], [544507]
Inhibitor (4-Methyl-2-oxo-2H-quinolin-1-yl)-acetic acid Drug Info [533420]
(6-Hydroxy-2-oxo-2H-quinolin-1-yl)-acetic acid Drug Info [533420]
(6-Methoxy-2-oxo-2H-quinolin-1-yl)-acetic acid Drug Info [533420]
(8-Hydroxy-2-oxo-2H-quinolin-1-yl)-acetic acid Drug Info [533420]
2'-Monophosphoadenosine 5'-Diphosphoribose Drug Info [551393]
2,3-dihydroxypropanal Drug Info [529225]
2-(3,4-Dihydroxy-benzyl)-7-hydroxy-chromen-4-one Drug Info [525506]
2-(3,4-Dihydroxy-phenyl)-7-hydroxy-chromen-4-one Drug Info [525506]
2-(3-benzoyl-1H-pyrrol-1-yl)acetic acid Drug Info [530758]
2-(4-aminophenylsulfonamido)acetic acid Drug Info [529308]
2-(Phenylsulfonamido)acetic Acid Drug Info [531207]
2-Benzhydryl-7-hydroxy-chromen-4-one Drug Info [525506]
2-Benzyl-7-hydroxy-chromen-4-one Drug Info [525506]
3,5-dichlorosalicylic acid Drug Info [529899]
3-(3-Benzoyl-1H-pyrrol-1-yl)propanoic acid Drug Info [530758]
3-[5-(3-nitrophenyl)thiophen-2-yl]propanoic acid Drug Info [551374]
4-(3-Benzoyl-1H-pyrrol-1-yl)butanoic acid Drug Info [530758]
4-(3-Methoxy-phenyl)-isoxazolidine-3,5-dione Drug Info [533567]
6,7-Dihydroxy-2-phenyl-chromen-4-one Drug Info [525506]
6-(1H-Indole-2-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(2-Bromo-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(2-Chloro-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(2-Fluoro-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(3-Chloro-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(4-Bromo-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(4-Chloro-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(4-Fluoro-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(4-Methoxy-benzenesulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(Benzofuran-2-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(Benzothiazole-2-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(Biphenyl-2-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(Naphthalene-1-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(Naphthalene-2-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-(Toluene-4-sulfonyl)-2H-pyridazin-3-one Drug Info [527771]
6-Benzenesulfonyl-2H-pyridazin-3-one Drug Info [527771]
6-Hydroxy-2-(4-hydroxy-benzyl)-chromen-4-one Drug Info [525506]
6-methoxykaempferol 3-O-beta-D-robinobioside Drug Info [533553]
6-Phenylmethanesulfonyl-2H-pyridazin-3-one Drug Info [527771]
7-Hydroxy-2-(4-hydroxy-benzyl)-chromen-4-one Drug Info [525506]
7-Hydroxy-2-(4-methoxy-benzyl)-chromen-4-one Drug Info [525506]
7-Hydroxy-4-phenylcoumarin Drug Info [531138]
7-Hydroxy-6-nitro-2-phenyl-chromen-4-one Drug Info [525506]
AD-5467 Drug Info [531314], [551871]
AK198 Drug Info [533225]
ALO-1567 Drug Info [530034], [551871]
Alpha-D-Glucose-6-Phosphate Drug Info [551393]
Alrestatin Drug Info [551393]
APIGENIN Drug Info [529340]
Apigenin-7-O-beta-D-glucuronide Drug Info [529340]
Apigenin-7-O-beta-D-glucuronide methyl ester Drug Info [529340]
ARI-809 Drug Info [528451]
ASTRAGALIN Drug Info [529340]
CHRYSIN Drug Info [530856]
CONTIGOSIDE B Drug Info [534149]
DIADZEIN Drug Info [525506]
Epalrestat Drug Info [535244], [537989]
EPALRESTATE Drug Info [529340]
Fidarestat Drug Info [535270], [538074]
Fidarestat(Stereoisomer) Drug Info [551393]
Hydroxydimethylarsine Oxide Drug Info [551393]
IDD552 Drug Info [551393]
IDD594 Drug Info [551374]
IMIRESTAT Drug Info [530231]
Inhibitor Idd 384 Drug Info [551393]
Isorhamnetin 3,7-disulfate Drug Info [534149]
Isorhamnetin 3-O-rhamnoside Drug Info [526409]
JTT-811 Drug Info [543707]
KAEMPFEROL Drug Info [529340]
LIDORESTAT Drug Info [527533]
M-16209 Drug Info [529323], [551871]
MANGIFERIN Drug Info [526834]
N-Acetylalanine Drug Info [551393]
NSC-94258 Drug Info [525506]
O5-Acetyl-O7-nitrooxyethyl chrysin Drug Info [530856]
O7-Nitrooxyethyl chrysin Drug Info [530856]
PALBINONE Drug Info [530306]
Patuletin 3-O-beta-D-galactoside Drug Info [533553]
Patuletin 3-O-beta-D-robinobioside Drug Info [533553]
Ponalrestat Drug Info [534948]
QR-333 Drug Info [527695]
Quercetin 3-O-neohesperidoside Drug Info [526409]
QUERCITRIN Drug Info [529340]
Ranirestat Drug Info [543707]
Sorbinil Drug Info [536032], [537789]
SPR-210 Drug Info [537904]
Sulindac Drug Info [537804], [537805]
Tamarixetin 3-glucoside-7-sulfate Drug Info [534149]
TINGENIN B Drug Info [526834]
TINGENONE Drug Info [526834]
Tolrestat Drug Info [537927]
TRIPTOCALLINE A Drug Info [526834]
Zenarestat Drug Info [535187]
Modulator BNV-222 Drug Info [543707]
CTL-102-GDEPT Drug Info [549941]
E-0722 Drug Info [533052]
FR-62765 Drug Info [529820]
MINALRESTAT Drug Info
T2c-003 Drug Info [543707]
WF-2421 Drug Info [529812]
ZOPOLRESTAT Drug Info
Target Expression Profile (TEP) and Drug Resistance Mutation (DRM)
TEP EXP Info
Pathways
BioCyc Pathway Methylglyoxal degradation III
Acetone degradation I (to methylglyoxal)
KEGG Pathway Pentose and glucuronate interconversions
Fructose and mannose metabolism
Galactose metabolism
Glycerolipid metabolism
Metabolic pathways
NetPath Pathway IL1 Signaling Pathway
TGF_beta_Receptor Signaling Pathway
PathWhiz Pathway Fructose and Mannose Degradation
Pyruvate Metabolism
Pterine Biosynthesis
Glycerolipid Metabolism
Galactose Metabolism
WikiPathways Metapathway biotransformation
Polyol Pathway
Metabolism of steroid hormones and vitamin D
References
Ref 521528ClinicalTrials.gov (NCT00043797) Lidorestat (IDD 676) for the Treatment of Diabetic Neuropathy. U.S. National Institutes of Health.
Ref 521626ClinicalTrials.gov (NCT00101426) Safety and Efficacy of AS-3201 in the Treatment of Diabetic Sensorimotor Polyneuropathy. U.S. National Institutes of Health.
Ref 521758ClinicalTrials.gov (NCT00252148) Safety and Immunogenicity of a Modified Vaccinia Ankara (MVA) HIV Vaccine in HIV Uninfected Adults. U.S. National Institutes of Health.
Ref 522174ClinicalTrials.gov (NCT00568035) Safety and Efficacy Study of QR-333 in Patient's With Symptomatic Diabetic Neuropathy. U.S. National Institutes of Health.
Ref 529812WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea. J Antibiot (Tokyo). 1991 Feb;44(2):130-5.
Ref 529820Studies on WF-3681, a novel aldose reductase inhibitor. IV. Effect of FR-62765, a derivative of WF-3681, on the diabetic neuropathy in rats. J Antibiot (Tokyo). 1991 Apr;44(4):441-4.
Ref 530034Metabolism of the aldose reductase inhibitor ALO1567 in man. Br J Clin Pharmacol. 1991 Aug;32(2):221-7.
Ref 530668Phase 1 safety and immunogenicity evaluation of ADMVA, a multigenic, modified vaccinia Ankara-HIV-1 B'/C candidate vaccine. PLoS One. 2010 Jan 25;5(1):e8816.
Ref 532182X-ray structure of the V301L aldo-keto reductase 1B10 complexed with NADP(+) and the potent aldose reductase inhibitor fidarestat: implications for inhibitor binding and selectivity. Chem Biol Interact. 2013 Feb 25;202(1-3):178-85.
Ref 534401Effect of tolrestat, an aldose reductase inhibitor, on neutrophil respiratory burst activity in diabetic patients. Metabolism. 1997 Jun;46(6):634-8.
Ref 536361Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. Epub 2007 Feb 20.
Ref 536772New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.
Ref 540828(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5425).
Ref 542427(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7404).
Ref 542435(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7411).
Ref 542439(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7415).
Ref 542442(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7418).
Ref 542443(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7419).
Ref 544507Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000004)
Ref 544510Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000008)
Ref 544513Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000017)
Ref 544515Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000020)
Ref 544516Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000031)
Ref 544806Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001173)
Ref 544842Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001300)
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Ref 545360Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003006)
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Ref 546958Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011583)
Ref 547576Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017463)
Ref 548845Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029470)
Ref 549081Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032059)
Ref 525506J Med Chem. 1999 Jun 3;42(11):1881-93.1-Benzopyran-4-one antioxidants as aldose reductase inhibitors.
Ref 526409J Nat Prod. 2002 Aug;65(8):1151-5.New flavonol oligoglycosides and polyacylated sucroses with inhibitory effects on aldose reductase and platelet aggregation from the flowers of Prunus mume.
Ref 526834J Nat Prod. 2003 Sep;66(9):1191-6.Structures of new friedelane-type triterpenes and eudesmane-type sesquiterpene and aldose reductase inhibitors from Salacia chinensis.
Ref 527533J Med Chem. 2005 May 5;48(9):3141-52.Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors of aldose reductase for treatment of chronic diabetic complications.
Ref 527695A multicenter, double-blind, safety study of QR-333 for the treatment of symptomatic diabetic peripheral neuropathy. A preliminary report. J Diabetes Complications. 2005 Sep-Oct;19(5):247-53.
Ref 527771J Med Chem. 2005 Oct 6;48(20):6326-39.A novel series of non-carboxylic acid, non-hydantoin inhibitors of aldose reductase with potent oral activity in diabetic rat models: 6-(5-chloro-3-methylbenzofuran-2-sulfonyl)-2H-pyridazin-3-one and congeners.
Ref 528451A selective aldose reductase inhibitor of a new structural class prevents or reverses early retinal abnormalities in experimental diabetic retinopathy. Diabetes. 2006 Oct;55(10):2757-62.
Ref 529225Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20764-9. Epub 2007 Dec 17.Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10.
Ref 529308Bioorg Med Chem. 2008 Apr 1;16(7):3926-32. Epub 2008 Jan 30.Design and synthesis of N-(3,5-difluoro-4-hydroxyphenyl)benzenesulfonamides as aldose reductase inhibitors.
Ref 529323Effects of novel aldose reductase inhibitors, M16209 and M16287, on streptozotocin-induced diabetic neuropathy in rats. Eur J Pharmacol. 1991 Feb 7;193(2):185-91.
Ref 529340J Nat Prod. 2008 Apr;71(4):713-5. Epub 2008 Feb 26.Erigeroflavanone, a flavanone derivative from the flowers of Erigeron annuus with protein glycation and aldose reductase inhibitory activity.
Ref 529812WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea. J Antibiot (Tokyo). 1991 Feb;44(2):130-5.
Ref 529820Studies on WF-3681, a novel aldose reductase inhibitor. IV. Effect of FR-62765, a derivative of WF-3681, on the diabetic neuropathy in rats. J Antibiot (Tokyo). 1991 Apr;44(4):441-4.
Ref 529899Bioorg Med Chem. 2009 Feb 1;17(3):1244-50. Epub 2008 Dec 24.Correlation of binding constants and molecular modelling of inhibitors in the active sites of aldose reductase and aldehyde reductase.
Ref 530034Metabolism of the aldose reductase inhibitor ALO1567 in man. Br J Clin Pharmacol. 1991 Aug;32(2):221-7.
Ref 530231J Med Chem. 1991 Nov;34(11):3229-34.Spiro[fluoreneisothiazolidin]one dioxides: new aldose reductase and L-hexonate dehydrogenase inhibitors.
Ref 530306J Nat Prod. 2009 Aug;72(8):1465-70.Inhibitors of aldose reductase and formation of advanced glycation end-products in moutan cortex (Paeonia suffruticosa).
Ref 530758Bioorg Med Chem. 2010 Mar 15;18(6):2107-14. Epub 2010 Feb 11.Design and synthesis of novel series of pyrrole based chemotypes and their evaluation as selective aldose reductase inhibitors. A case ofbioisosterism between a carboxylic acid moiety and that of a tetrazole.
Ref 530856Bioorg Med Chem. 2010 May 1;18(9):3020-5. Epub 2010 Mar 27.Synthesis, characterization and vasculoprotective effects of nitric oxide-donating derivatives of chrysin.
Ref 531138Bioorg Med Chem Lett. 2010 Oct 1;20(19):5630-3. Epub 2010 Aug 12.6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2.
Ref 531207J Med Chem. 2010 Nov 11;53(21):7756-66.A diverse series of substituted benzenesulfonamides as aldose reductase inhibitors with antioxidant activity: design, synthesis, and in vitro activity.
Ref 531314Studies on antidiabetic agents. IX. A new aldose reductase inhibitor, AD-5467, and related 1,4-benzoxazine and 1,4-benzothiazine derivatives: synthesis and biological activity. Chem Pharm Bull (Tokyo). 1990 May;38(5):1238-45.
Ref 533052Aldose reductase inhibitors and prevention of galactose cataracts in rats. Invest Ophthalmol Vis Sci. 1989 Jul;30(7):1623-32.
Ref 533225The Effect of Halogen-to-Hydrogen Bond Substitution on Human Aldose Reductase Inhibition. ACS Chem Biol. 2015 Jul 17;10(7):1637-42.
Ref 533420J Med Chem. 1986 Oct;29(10):2024-8.Synthesis and aldose reductase inhibitory activity of substituted 2-oxoquinoline-1-acetic acid derivatives.
Ref 533553J Nat Prod. 1984 Mar-Apr;47(2):316-9.Flavonoids with anti-cataract activity from Brickellia arguta.
Ref 533567J Med Chem. 1982 Jun;25(6):745-7.Isoxazolidine-3,5-diones as lens aldose reductase inhibitors.
Ref 534149J Nat Prod. 1996 Apr;59(4):443-5.Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes.
Ref 534948Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice. Anticancer Res. 1999 Sep-Oct;19(5B):4105-11.
Ref 535187The effects of zenarestat, an aldose reductase inhibitor, on minimal F-wave latency and nerve blood flow in streptozotocin-induced diabetic rats. Life Sci. 2001 Feb 9;68(12):1439-48.
Ref 535244Long-term effect of epalrestat, an aldose reductase inhibitor, on the development of incipient diabetic nephropathy in Type 2 diabetic patients. J Diabetes Complications. 2001 Sep-Oct;15(5):241-4.
Ref 535270Clinical efficacy of fidarestat, a novel aldose reductase inhibitor, for diabetic peripheral neuropathy: a 52-week multicenter placebo-controlled double-blind parallel group study. Diabetes Care. 2001 Oct;24(10):1776-82.
Ref 536032Recent clinical experience with aldose reductase inhibitors. J Diabetes Complications. 1992 Jan-Mar;6(1):39-44.
Ref 537789A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes. 1983 Oct;32(10):938-42.
Ref 537804Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.
Ref 537805Diabetic complications in lens and nerve and their prevention by sulindac or sorbinil: two novel aldose reductase inhibitors. Invest Ophthalmol Vis Sci. 1983 Oct;24(10):1426-9.
Ref 537904Pharmacological profiles of a novel aldose reductase inhibitor, SPR-210, and its effects on streptozotocin-induced diabetic rats. Jpn J Pharmacol. 1994 Feb;64(2):115-24.
Ref 537927Aldose reductase inhibitors: an update. Ann Pharmacother. 1993 Jun;27(6):751-4.
Ref 537989Clinical investigation of epalrestat, an aldose reductase inhibitor, on diabetic neuropathy in Japan: multicenter study. Diabetic Neuropathy Study Group in Japan. J Diabetes Complications. 1996 May-Jun;10(3):168-72.
Ref 538074Aldose reductase inhibitor SNK-860. Nippon Rinsho. 1997 Nov;55 Suppl:212-5.
Ref 543707(http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 2768).
Ref 549941Genes in the Service of Therapeutic Index: Progress for Virus-Directed Enzyme Prodrug Therapy. JCO May 1, 2004 vol. 22 no. 9 1535-1537c.
Ref 551374The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
Ref 551393How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
Ref 551871Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

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