Target Information

Target General Information

Top

Target ID

T26623 (Former ID: TTDS00115)

Target Name

Aldose reductase (AKR1B1)

Synonyms

Aldehyde reductase; AKR1B1

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Gene Name

AKR1B1

Target Type

Successful target

[1]

Disease

[+] 2 Target-related Diseases

Neuropathy [ICD-11: 8C0Z]

Rheumatoid arthritis [ICD-11: FA20]

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.

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BioChemical Class

Short-chain dehydrogenases reductase

UniProt ID

ALDR_HUMAN

EC Number

EC 1.1.1.300

Sequence

MASRLLLNNGAKMPILGLGTWKSPPGQVTEAVKVAIDVGYRHIDCAHVYQNENEVGVAIQ
EKLREQVVKREELFIVSKLWCTYHEKGLVKGACQKTLSDLKLDYLDLYLIHWPTGFKPGK
EFFPLDESGNVVPSDTNILDTWAAMEELVDEGLVKAIGISNFNHLQVEMILNKPGLKYKP
AVNQIECHPYLTQEKLIQYCQSKGIVVTAYSPLGSPDRPWAKPEDPSLLEDPRIKAIAAK
HNKTTAQVLIRFPMQRNLVVIPKSVTPERIAENFKVFDFELSSQDMTTLLSYNRNWRVCA
LLSCTSHKDYPFHEEF

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3D Structure

Click to Show 3D Structure of This Target

PDB

HIT2.0 ID

T68NCI

Drugs and Modes of Action

Top

Approved Drug(s)

[+] 2 Approved Drugs

Epalrestat

Drug Info

Approved

Diabetic neuropathy

[2]

Sulindac

Drug Info

Approved

Rheumatoid arthritis

[3], [4]

Clinical Trial Drug(s)

[+] 11 Clinical Trial Drugs

Fidarestat

Drug Info

Phase 3

Diabetic complication

[5]

Ranirestat

Drug Info

Phase 3

Diabetic neuropathy

[6]

BNV-222

Drug Info

Phase 2/3

Diabetic neuropathy

[7]

CONTIGOSIDE B

Drug Info

Phase 2/3

Thrombosis

[8]

ADMVA

Drug Info

Phase 2

Diabetic complication

[9], [10]

LIDORESTAT

Drug Info

Phase 2

Diabetic complication

[11], [12]

M-16209

Drug Info

Phase 2

Diabetic complication

[13]

QR-333

Drug Info

Phase 2

Diabetic neuropathy

[14]

T2c-003

Drug Info

Phase 1/2

Diabetic neuropathy

[15]

ALO-1567

Drug Info

Phase 1

Glaucoma/ocular hypertension

[16]

SSR-125047

Drug Info

Phase 1

Schizophrenia

[17]

Discontinued Drug(s)

[+] 13 Discontinued Drugs

IMIRESTAT

Drug Info

Discontinued in Phase 3

Diabetic complication

[18]

MINALRESTAT

Drug Info

Discontinued in Phase 3

Diabetic complication

[19]

Ponalrestat

Drug Info

Discontinued in Phase 3

Gout

[20]

AD-5467

Drug Info

Discontinued in Phase 2

Diabetic complication

[21]

CTL-102-GDEPT

Drug Info

Discontinued in Phase 2

Head and neck cancer

[22]

JTT-811

Drug Info

Discontinued in Phase 2

Diabetic complication

[23]

ZOPOLRESTAT

Drug Info

Discontinued in Phase 2

Diabetic complication

[24], [25]

E-0722

Drug Info

Terminated

Diabetic cataract

[27]

FR-62765

Drug Info

Terminated

Diabetic complication

[28]

Sorbinil

Drug Info

Terminated

Diabetic cataract

[29], [30]

SPR-210

Drug Info

Terminated

Diabetic complication

[31]

WF-2421

Drug Info

Terminated

Diabetic complication

[32]

Zenarestat

Drug Info

Terminated

Diabetic neuropathy

[33], [34]

Preclinical Drug(s)

[+] 1 Preclinical Drugs

ARI-809

Drug Info

Preclinical

Diabetic complication

[26]

Mode of Action

[+] 2 Modes of Action

Inhibitor

[+] 93 Inhibitor drugs

Epalrestat

Drug Info

[35], [36]

Sulindac

Drug Info

[1], [37]

Fidarestat

Drug Info

[38], [39]

Ranirestat

Drug Info

[40]

BNV-222

Drug Info

[7]

CONTIGOSIDE B

Drug Info

[41]

LIDORESTAT

Drug Info

[42]

M-16209

Drug Info

[43], [44]

QR-333

Drug Info

[45]

ALO-1567

Drug Info

[16], [44]

SSR-125047

Drug Info

[46]

IMIRESTAT

Drug Info

[47]

Ponalrestat

Drug Info

[49]

AD-5467

Drug Info

[44], [50]

Alrestatin

Drug Info

[51]

JTT-811

Drug Info

[40]

ARI-809

Drug Info

[54]

Sorbinil

Drug Info

[56], [57]

SPR-210

Drug Info

[58]

Zenarestat

Drug Info

[59]

(4-Methyl-2-oxo-2H-quinolin-1-yl)-acetic acid

Drug Info

[60]

(6-Hydroxy-2-oxo-2H-quinolin-1-yl)-acetic acid

Drug Info

[60]

(6-Methoxy-2-oxo-2H-quinolin-1-yl)-acetic acid

Drug Info

[60]

(8-Hydroxy-2-oxo-2H-quinolin-1-yl)-acetic acid

Drug Info

[60]

2'-Monophosphoadenosine 5'-Diphosphoribose

Drug Info

[51]

2,3-dihydroxypropanal

Drug Info

[61]

2-(3,4-Dihydroxy-benzyl)-7-hydroxy-chromen-4-one

Drug Info

[62]

2-(3,4-Dihydroxy-phenyl)-7-hydroxy-chromen-4-one

Drug Info

[62]

2-(3-benzoyl-1H-pyrrol-1-yl)acetic acid

Drug Info

[63]

2-(4-aminophenylsulfonamido)acetic acid

Drug Info

[64]

2-(Phenylsulfonamido)acetic Acid

Drug Info

[65]

2-Benzhydryl-7-hydroxy-chromen-4-one

Drug Info

[62]

2-Benzyl-7-hydroxy-chromen-4-one

Drug Info

[62]

3,5-dichlorosalicylic acid

Drug Info

[66]

3-(3-Benzoyl-1H-pyrrol-1-yl)propanoic acid

Drug Info

[63]

3-[5-(3-nitrophenyl)thiophen-2-yl]propanoic acid

Drug Info

[67]

4-(3-Benzoyl-1H-pyrrol-1-yl)butanoic acid

Drug Info

[63]

4-(3-Methoxy-phenyl)-isoxazolidine-3,5-dione

Drug Info

[68]

6,7-Dihydroxy-2-phenyl-chromen-4-one

Drug Info

[62]

6-(1H-Indole-2-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(2-Bromo-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(2-Chloro-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(2-Fluoro-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(3-Chloro-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(4-Bromo-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(4-Chloro-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(4-Fluoro-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(4-Methoxy-benzenesulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(Benzofuran-2-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(Benzothiazole-2-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(Biphenyl-2-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(Naphthalene-1-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(Naphthalene-2-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-(Toluene-4-sulfonyl)-2H-pyridazin-3-one

Drug Info

[69]

6-Benzenesulfonyl-2H-pyridazin-3-one

Drug Info

[69]

6-Hydroxy-2-(4-hydroxy-benzyl)-chromen-4-one

Drug Info

[62]

6-methoxykaempferol 3-O-beta-D-robinobioside

Drug Info

[70]

6-Phenylmethanesulfonyl-2H-pyridazin-3-one

Drug Info

[69]

7-Hydroxy-2-(4-hydroxy-benzyl)-chromen-4-one

Drug Info

[62]

7-Hydroxy-2-(4-methoxy-benzyl)-chromen-4-one

Drug Info

[62]

7-Hydroxy-4-phenylcoumarin

Drug Info

[71]

7-Hydroxy-6-nitro-2-phenyl-chromen-4-one

Drug Info

[62]

AK198

Drug Info

[72]

Alpha-D-Glucose-6-Phosphate

Drug Info

[51]

APIGENIN

Drug Info

[73]

Apigenin-7-O-beta-D-glucuronide

Drug Info

[73]

Apigenin-7-O-beta-D-glucuronide methyl ester

Drug Info

[73]

ASTRAGALIN

Drug Info

[73]

Chrysin

Drug Info

[74]

daidzein

Drug Info

[62]

EPALRESTATE

Drug Info

[73]

Fidarestat(Stereoisomer)

Drug Info

[51]

Hydroxydimethylarsine Oxide

Drug Info

[51]

IDD552

Drug Info

[51]

IDD594

Drug Info

[67]

Inhibitor Idd 384

Drug Info

[51]

Isorhamnetin 3,7-disulfate

Drug Info

[41]

Isorhamnetin 3-O-rhamnoside

Drug Info

[75]

KAEMPFEROL

Drug Info

[73]

MANGIFERIN

Drug Info

[76]

N-Acetylalanine

Drug Info

[51]

NSC-94258

Drug Info

[62]

O5-Acetyl-O7-nitrooxyethyl chrysin

Drug Info

[74]

O7-Nitrooxyethyl chrysin

Drug Info

[74]

PALBINONE

Drug Info

[77]

Patuletin 3-O-beta-D-galactoside

Drug Info

[70]

Patuletin 3-O-beta-D-robinobioside

Drug Info

[70]

Quercetin 3-O-neohesperidoside

Drug Info

[75]

QUERCITRIN

Drug Info

[73]

Tamarixetin 3-glucoside-7-sulfate

Drug Info

[41]

TINGENIN B

Drug Info

[76]

TINGENONE

Drug Info

[76]

TRIPTOCALLINE A

Drug Info

[76]

Modulator

[+] 8 Modulator drugs

T2c-003

Drug Info

[40]

MINALRESTAT

Drug Info

[48]

CTL-102-GDEPT

Drug Info

[52]

ZOPOLRESTAT

Drug Info

[53]

E-0722

Drug Info

[55]

FR-62765

Drug Info

[28]

WF-2421

Drug Info

[32]

BNV-222

Drug Info

[40]

Cell-based Target Expression Variations

Top

Cell-based Target Expression Variations

Cell-based Target Expression Variations Info

Drug Binding Sites of Target

Top

Ligand Name: Tolmetin

Ligand Info

Structure Description

Crystal Structure of Human Aldose Reductase Complexed with Tolmetin

PDB:3S3G

Method

X-ray diffraction

Resolution

1.80 Å

Mutation

[78]

PDB Sequence

MASRLLLNNG

⁹

AKMPILGLGT

¹⁹

WKSPPGQVTE

²⁹

AVKVAIDVGY

³⁹

RHIDCAHVYQ

⁴⁹

NENEVGVAIQ

⁵⁹

EKLREQVVKR

⁶⁹

EELFIVSKLW

⁷⁹

CTYHEKGLVK

⁸⁹

GACQKTLSDL

⁹⁹

KLDYLDLYLI

¹⁰⁹

HWPTGFKPGK

¹¹⁹

EFFPLDESGN

¹²⁹

VVPSDTNILD

¹³⁹

TWAAMEELVD

¹⁴⁹

EGLVKAIGIS

¹⁵⁹

NFNHLQVEMI

¹⁶⁹

LNKPGLKYKP

¹⁷⁹

AVNQIECHPY

¹⁸⁹

LTQEKLIQYC

¹⁹⁹

QSKGIVVTAY

²⁰⁹

SPLGSPDRPW

²¹⁹

AKPEDPSLLE

²²⁹

DPRIKAIAAK

²³⁹

HNKTTAQVLI

²⁴⁹

RFPMQRNLVV

²⁵⁹

IPKSVTPERI

²⁶⁹

AENFKVFDFE

²⁷⁹

LSSQDMTTLL

²⁸⁹

SYNRNWRVCA

²⁹⁹

LLSCTSHKDY

³⁰⁹

PFHEEF

Residue

Distance (Å)

TRP20

3.421

VAL47

4.166

TYR48

2.893

TRP79

4.300

HIS110

2.742

Residue

Distance (Å)

TRP111

2.923

PHE122

3.363

TRP219

3.602

CYS298

3.953

Ligand Name: Nitazoxanide

Ligand Info

Structure Description

Aldose reductase complexed with a nitro compound

PDB:3V35

Method

X-ray diffraction

Resolution

1.90 Å

Mutation

[79]

PDB Sequence

MASRLLLNNG

⁹

AKMPILGLGT

¹⁹

WKSPPGQVTE

²⁹

AVKVAIDVGY

³⁹

RHIDCAHVYQ

⁴⁹

NENEVGVAIQ

⁵⁹

EKLREQVVKR

⁶⁹

EELFIVSKLW

⁷⁹

CTYHEKGLVK

⁸⁹

GACQKTLSDL

⁹⁹

KLDYLDLYLI

¹⁰⁹

HWPTGFKPGK

¹¹⁹

EFFPLDESGN

¹²⁹

VVPSDTNILD

¹³⁹

TWAAMEELVD

¹⁴⁹

EGLVKAIGIS

¹⁵⁹

NFNHLQVEMI

¹⁶⁹

LNKPGLKYKP

¹⁷⁹

AVNQIECHPY

¹⁸⁹

LTQEKLIQYC

¹⁹⁹

QSKGIVVTAY

²⁰⁹

SPLGSPDRPW

²¹⁹

AKPEDPSLLE

²²⁹

DPRIKAIAAK

²³⁹

HNKTTAQVLI

²⁴⁹

RFPMQRNLVV

²⁵⁹

IPKSVTPERI

²⁶⁹

AENFKVFDFE

²⁷⁹

LSSQDMTTLL

²⁸⁹

SYNRNWRVCA

²⁹⁹

LLSCTSHKDY

³⁰⁹

PFHEEF

Residue

Distance (Å)

TRP20

3.406

VAL47

3.559

TYR48

4.492

TRP79

3.259

HIS110

3.313

Residue

Distance (Å)

TRP111

3.366

PHE122

3.864

PRO218

3.648

TRP219

3.416

LEU300

4.765

Click to View More Binding Site Information of This Target with Different Ligands

Different Human System Profiles of Target	Top
Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target. A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020). Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues. The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021). Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function. Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006). Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database. The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017). Human Similarity Proteins Human Tissue Distribution Human Pathway Affiliation Biological Network Descriptors

Different Human System Profiles of Target

Top

Human Similarity Proteins of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.

A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs (Brief Bioinform, 21: 649-662, 2020).

Human Tissue Distribution of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.

The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects (Nat Rev Drug Discov, 20: 64-81, 2021).

Human Pathway Affiliation of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.

Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes (Pharmacol Rev, 58: 259-279, 2006).

Biological Network Descriptors of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.

The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information (Front Pharmacol, 9, 1245, 2018; Curr Opin Struct Biol. 44:134-142, 2017).

Human Similarity Proteins

Human Tissue Distribution

Human Pathway Affiliation

Biological Network Descriptors

There is no similarity protein (E value < 0.005) for this target


Note: If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.

KEGG Pathway	Pathway ID	Affiliated Target
Pentose and glucuronate interconversions	hsa00040	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Fructose and mannose metabolism	hsa00051	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Galactose metabolism	hsa00052	Affiliated Target
Class: Metabolism => Carbohydrate metabolism	Pathway Hierarchy
Glycerolipid metabolism	hsa00561	Affiliated Target
Class: Metabolism => Lipid metabolism	Pathway Hierarchy
Folate biosynthesis	hsa00790	Affiliated Target
Class: Metabolism => Metabolism of cofactors and vitamins	Pathway Hierarchy

Degree	5	Degree centrality	5.37E-04	Betweenness centrality	3.52E-04
Closeness centrality	1.79E-01	Radiality	1.29E+01	Clustering coefficient	3.00E-01
Neighborhood connectivity	8.20E+00	Topological coefficient	2.44E-01	Eccentricity	11
Download	Click to Download the Full PPI Network of This Target

Chemical Structure based Activity Landscape of Target

Top

Drug Property Profile of Target

Top

(1) Molecular Weight (mw) based Drug Clustering

(2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering

(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering

(4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering

(5) Rotatable Bond Count (rotbonds) based Drug Clustering

(6) Topological Polar Surface Area (polararea) based Drug Clustering

"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five

Co-Targets

Top

Co-Targets

Co-Targets Info

Target Poor or Non Binders

Top

Target Poor or Non Binders

Target Poor or Non Binders Info

Target Profiles in Patients

Top

Target Expression
Profile (TEP)

Target Expression Profile Info

Target Affiliated Biological Pathways

Top

BioCyc

[+] 2 BioCyc Pathways

Methylglyoxal degradation III

Acetone degradation I (to methylglyoxal)

KEGG Pathway

[+] 5 KEGG Pathways

Pentose and glucuronate interconversions

Fructose and mannose metabolism

Galactose metabolism

Glycerolipid metabolism

Metabolic pathways

NetPath Pathway

[+] 2 NetPath Pathways

IL1 Signaling Pathway

TGF_beta_Receptor Signaling Pathway

Pathwhiz Pathway

[+] 5 Pathwhiz Pathways

Fructose and Mannose Degradation

Pyruvate Metabolism

Pterine Biosynthesis

Glycerolipid Metabolism

Galactose Metabolism

WikiPathways

[+] 3 WikiPathways

Metapathway biotransformation

Polyol Pathway

Metabolism of steroid hormones and vitamin D

Target-Related Models and Studies

Top

Target Validation

Target Validation Info

Target QSAR Model

References

Top

REF 1

Inhibition of human lens aldose reductase by flavonoids, sulindac and indomethacin. Biochem Pharmacol. 1983 Jul 1;32(13):1995-8.

REF 2

Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.

REF 3

URL: 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 4

New drugs in development for the treatment of endometriosis. Expert Opin Investig Drugs. 2008 Aug;17(8):1187-202.

REF 5

X-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 6

ClinicalTrials.gov (NCT00101426) Safety and Efficacy of AS-3201 in the Treatment of Diabetic Sensorimotor Polyneuropathy. U.S. National Institutes of Health.

REF 7

ClinicalTrials.gov (NCT02332005) 12-Month Efficacy and Safety of Diepalrestat in Adults With Diabetic Peripheral Neuropathy, a DB, Placebo-Controlled Study (DE-DPN). U.S. National Institutes of Health.

REF 8

Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)

REF 9

ClinicalTrials.gov (NCT00252148) Safety and Immunogenicity of a Modified Vaccinia Ankara (MVA) HIV Vaccine in HIV Uninfected Adults. U.S. National Institutes of Health.

REF 10

Phase 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 11

REF 12

ClinicalTrials.gov (NCT00043797) Lidorestat (IDD 676) for the Treatment of Diabetic Neuropathy. U.S. National Institutes of Health.

REF 13

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000031)

REF 14

ClinicalTrials.gov (NCT00568035) Safety and Efficacy Study of QR-333 in Patient's With Symptomatic Diabetic Neuropathy. U.S. National Institutes of Health.

REF 15

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800029470)

REF 16

Metabolism of the aldose reductase inhibitor ALO1567 in man. Br J Clin Pharmacol. 1991 Aug;32(2):221-7.

REF 17

The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.

REF 18

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000020)

REF 19

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800003006)

REF 20

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000017)

REF 21

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001300)

REF 22

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800011583)

REF 23

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800017463)

REF 24

REF 25

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800001173)

REF 26

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032059)

REF 27

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800004685)

REF 28

Studies 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 29

REF 30

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000008)

REF 31

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800002923)

REF 32

WF-2421, a new aldose reductase inhibitor produced from a fungus, Humicola grisea. J Antibiot (Tokyo). 1991 Feb;44(2):130-5.

REF 33

REF 34

Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800000004)

REF 35

Long-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 36

Clinical 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 37

Diabetic 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 38

Clinical 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 39

Aldose reductase inhibitor SNK-860. Nippon Rinsho. 1997 Nov;55 Suppl:212-5.

REF 40

REF 41

Effect of Polygonum hydropiper sulfated flavonoids on lens aldose reductase and related enzymes. J Nat Prod. 1996 Apr;59(4):443-5.

REF 42

Discovery of 3-[(4,5,7-trifluorobenzothiazol-2-yl)methyl]indole-N-acetic acid (lidorestat) and congeners as highly potent and selective inhibitors ... J Med Chem. 2005 May 5;48(9):3141-52.

REF 43

Effects 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 44

Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015

REF 45

A 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 46

Aldose reductase inhibitors: an update. Ann Pharmacother. 1993 Jun;27(6):751-4.

REF 47

Spiro[fluoreneisothiazolidin]one dioxides: new aldose reductase and L-hexonate dehydrogenase inhibitors. J Med Chem. 1991 Nov;34(11):3229-34.

REF 48

Minalrestat, an aldose reductase inhibitor, corrects the impaired microvascular reactivity in diabetes. J Pharmacol Exp Ther. 2003 Mar;304(3):1236-42.

REF 49

Ponalrestat, an aldose reductase inhibitor, inhibits cachexia syndrome induced by colon26 adenocarcinoma in mice. Anticancer Res. 1999 Sep-Oct;19(5B):4105-11.

REF 50

Studies 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 51

How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.

REF 52

Genes in the Service of Therapeutic Index: Progress for Virus-Directed Enzyme Prodrug Therapy. JCO May 1, 2004 vol. 22 no. 9 1535-1537c.

REF 53

Comparison of the effects of Zopolrestat and Sorbinil on lens myo-inositol influx. Pharmacology. 1997 Feb;54(2):76-83.

REF 54

A 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 55

Aldose reductase inhibitors and prevention of galactose cataracts in rats. Invest Ophthalmol Vis Sci. 1989 Jul;30(7):1623-32.

REF 56

A controlled trial of sorbinil, an aldose reductase inhibitor, in chronic painful diabetic neuropathy. Diabetes. 1983 Oct;32(10):938-42.

REF 57

Recent clinical experience with aldose reductase inhibitors. J Diabetes Complications. 1992 Jan-Mar;6(1):39-44.

REF 58

Pharmacological 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 59

The 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 60

Synthesis and aldose reductase inhibitory activity of substituted 2-oxoquinoline-1-acetic acid derivatives. J Med Chem. 1986 Oct;29(10):2024-8.

REF 61

Structural basis for the high all-trans-retinaldehyde reductase activity of the tumor marker AKR1B10. Proc Natl Acad Sci U S A. 2007 Dec 26;104(52):20764-9.

REF 62

1-Benzopyran-4-one antioxidants as aldose reductase inhibitors. J Med Chem. 1999 Jun 3;42(11):1881-93.

REF 63

Design and synthesis of novel series of pyrrole based chemotypes and their evaluation as selective aldose reductase inhibitors. A case of bioisoste... Bioorg Med Chem. 2010 Mar 15;18(6):2107-2114.

REF 64

Design and synthesis of N-(3,5-difluoro-4-hydroxyphenyl)benzenesulfonamides as aldose reductase inhibitors. Bioorg Med Chem. 2008 Apr 1;16(7):3926-32.

REF 65

A diverse series of substituted benzenesulfonamides as aldose reductase inhibitors with antioxidant activity: design, synthesis, and in vitro activ... J Med Chem. 2010 Nov 11;53(21):7756-66.

REF 66

Correlation of binding constants and molecular modelling of inhibitors in the active sites of aldose reductase and aldehyde reductase. Bioorg Med Chem. 2009 Feb 1;17(3):1244-50.

REF 67

The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.

REF 68

Isoxazolidine-3,5-diones as lens aldose reductase inhibitors. J Med Chem. 1982 Jun;25(6):745-7.

REF 69

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... J Med Chem. 2005 Oct 6;48(20):6326-39.

REF 70

Flavonoids with anti-cataract activity from Brickellia arguta. J Nat Prod. 1984 Mar-Apr;47(2):316-9.

REF 71

6,7-Dihydroxy-4-phenylcoumarin as inhibitor of aldose reductase 2. Bioorg Med Chem Lett. 2010 Oct 1;20(19):5630-3.

REF 72

The Effect of Halogen-to-Hydrogen Bond Substitution on Human Aldose Reductase Inhibition. ACS Chem Biol. 2015 Jul 17;10(7):1637-42.

REF 73

Erigeroflavanone, a flavanone derivative from the flowers of Erigeron annuus with protein glycation and aldose reductase inhibitory activity. J Nat Prod. 2008 Apr;71(4):713-5.

REF 74

Synthesis, characterization and vasculoprotective effects of nitric oxide-donating derivatives of chrysin. Bioorg Med Chem. 2010 May 1;18(9):3020-5.

REF 75

New flavonol oligoglycosides and polyacylated sucroses with inhibitory effects on aldose reductase and platelet aggregation from the flowers of Pru... J Nat Prod. 2002 Aug;65(8):1151-5.

REF 76

Structures of new friedelane-type triterpenes and eudesmane-type sesquiterpene and aldose reductase inhibitors from Salacia chinensis. J Nat Prod. 2003 Sep;66(9):1191-6.

REF 77

Inhibitors of aldose reductase and formation of advanced glycation end-products in moutan cortex (Paeonia suffruticosa). J Nat Prod. 2009 Aug;72(8):1465-70.

REF 78

The molecular basis for inhibition of sulindac and its metabolites towards human aldose reductase. FEBS Lett. 2012 Jan 2;586(1):55-9.

REF 79

Partial inhibition of aldose reductase by nitazoxanide and its molecular basis. ChemMedChem. 2012 Nov;7(11):1921-3.

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