epalrestat and zopolrestat

epalrestat has been researched along with zopolrestat* in 2 studies

Other Studies

2 other study(ies) available for epalrestat and zopolrestat

Article	Year
Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: role of Trp112 (Trp111). FEBS letters, 2013, Nov-15, Volume: 587, Issue:22 The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation. Topics: Aldehyde Reductase; Aldo-Keto Reductases; Benzothiazoles; Catalytic Domain; Crystallography, X-Ray; Enzyme Inhibitors; Flufenamic Acid; Hydrogen Bonding; Imidazolidines; Models, Molecular; Naphthalenes; Oleanolic Acid; Phthalazines; Protein Binding; Protein Structure, Secondary; Rhodanine; Structural Homology, Protein; Thiazolidines; Tryptophan	2013
Highly selective aldose reductase inhibitors. 3. Structural diversity of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids. Journal of medicinal chemistry, 1997, Feb-28, Volume: 40, Issue:5 Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4- dioxopyrimidine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition. Topics: Acetates; Aldehyde Reductase; Animals; Benzothiazoles; Diabetes Complications; Enzyme Inhibitors; Humans; Imidazoles; Kidney; Lens, Crystalline; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Phthalazines; Pyrimidinones; Rats; Sorbitol; Structure-Activity Relationship; Thiazoles	1997

Article

Year

Inhibitor selectivity between aldo-keto reductase superfamily members AKR1B10 and AKR1B1: role of Trp112 (Trp111).

FEBS letters, 2013, Nov-15, Volume: 587, Issue:22

The antineoplastic target aldo-keto reductase family member 1B10 (AKR1B10) and the critical polyol pathway enzyme aldose reductase (AKR1B1) share high structural similarity. Crystal structures reported here reveal a surprising Trp112 native conformation stabilized by a specific Gln114-centered hydrogen bond network in the AKR1B10 holoenzyme, and suggest that AKR1B1 inhibitors could retain their binding affinities toward AKR1B10 by inducing Trp112 flip to result in an "AKR1B1-like" active site in AKR1B10, while selective AKR1B10 inhibitors can take advantage of the broader active site of AKR1B10 provided by the native Trp112 side-chain orientation.

Topics: Aldehyde Reductase; Aldo-Keto Reductases; Benzothiazoles; Catalytic Domain; Crystallography, X-Ray; Enzyme Inhibitors; Flufenamic Acid; Hydrogen Bonding; Imidazolidines; Models, Molecular; Naphthalenes; Oleanolic Acid; Phthalazines; Protein Binding; Protein Structure, Secondary; Rhodanine; Structural Homology, Protein; Thiazolidines; Tryptophan

2013

Highly selective aldose reductase inhibitors. 3. Structural diversity of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids.

Journal of medicinal chemistry, 1997, Feb-28, Volume: 40, Issue:5

Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4- dioxopyrimidine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition.

Topics: Acetates; Aldehyde Reductase; Animals; Benzothiazoles; Diabetes Complications; Enzyme Inhibitors; Humans; Imidazoles; Kidney; Lens, Crystalline; Magnetic Resonance Spectroscopy; Models, Molecular; Molecular Structure; Phthalazines; Pyrimidinones; Rats; Sorbitol; Structure-Activity Relationship; Thiazoles

1997