Aldose Reductase Inhibitor

Isoliquiritigenin is an anti-tumor flavonoid from the root of Glycyrrhiza uralensis Fisch., which inhibits aldose reductase with an IC₅₀ of 320 nM. Isoliquiritigenin is a potent inhibitor of influenza virus replication with an EC₅₀ of 24.7 μM.

Epalrestat is an orally active aldose reductase inhibitor that acts on diabetic neuropathy.

Poliumoside, a caffeoylated phenylpropanoid glycoside, is isolated from Brandisia hancei stems and leaves. Poliumoside is an advanced glycation end product (AGE) formation and rat lens aldose reductase (RLAR) inhibitor, with IC₅₀s of 19.69 and 8.47 μM, respectively. Poliumoside also has antiinflammatory and antioxidant activity.

MitoBloCK-6 is a potent Erv1/ALR inhibitor, with an IC₅₀ of 900 nM and 700 nM, respectively. MitoBloCK-6 also inhibits Erv2 (IC₅₀=1.4 μM). MitoBloCK-6 can induce Apoptosis via cytochrome c release. MitoBloCK-6 inhibits growth of developing zebrafish motor neurons. MitoBloCK-6 has anticancer activity against liver cancer and leukemia.

Fidarestat (SNK 860) is an inhibitor of aldose reductase, with IC₅₀s of 26 nM, 33 μM, and 1.8 μM for aldose reductase, AKR1B10 and V301L AKR1B10, respectively; Fidarestat (SNK 860) has the potential to treat diabetic disease.

ALR2/α-Glucosidase-IN-1 (Compound 4) is a competitive ALR2 inhibitor and competitive α-glucosidase inhibitor, with an IC₅₀ of 0.250 μM against ALR2 and an IC₅₀ of 0.561 μM against α-glucosidase. ALR2/α-Glucosidase-IN-1 binds to the active sites of ALR2 and α-glucosidase, and inhibits enzymatic activity by competing with their respective substrates. ALR2/α-Glucosidase-IN-1 can be used in diabetes-related research.

Cemtirestat (CMTI) is a carboxymethylated thiatriazinoindole inhibitor of aldose reductase (ALR2). Cemtirestat potently inhibits rat ocular lens ALR2 with an IC₅₀ of 0.116 μM, and exhibits a 302-fold selectivity for rat kidney ALR1. Cemtirestat is applicable to the research of advanced diabetic complications.

AZ-11665362 is a CRTh2 (DP2) receptor antagonist with an IC₅₀ of 2.6 nM. AZ-11665362 shows weak activity against aldose reductase, serotonin transporter, CYP 2C19, and CYP 2C9. AZ-11665362 lacks measurable inhibitory activity against COX-1 and COX-2. AZ-11665362 can be used for the research of asthma, and other inflammatory diseases.

AKR1B10-IN-1 is a potent inhibitor of AKR1B10 (Aldo-Keto Reductase 1B10) with an IC₅₀ of 3.5 nM. AKR1B10-IN-1 suppresses proliferation, metastasis, and Cisplatin (CDDP) resistance of lung cancer cells.

β-Glucogallin is an orally active and selective aldose reductase (AKR1B1) inhibitor with an IC₅₀ value of 58 μM when using Glyceraldehyde (HY-128748) as AKR1B1 substrate. β-Glucogallin reduces ROS, PDGF, RAGE, and NF-κB. β-Glucogallin increases SOD. β-Glucogallin has antioxidant and hepatoprotective effects. β-Glucogallin can be used in retinal research.

Ponalrestat (ICI 128436) is an orally active, selective and noncompetitive aldose reductase (AKR1B1; ALR) inhibitor. Ponalrestat selectively inhibits ALR2 (K_i=7.7 nM) over ALR1 (K_i=60 μM). Ponalrestat inhibits the conversion of glucose to sorbitol.

Sorbinil is an aldose reductase inhibitor (ARI) that prevents the accumulation of sorbitol in cells or animals. Sorbinil is useful in studying diabetes and diabetic complications, reducing AR activity and inhibiting the polyol pathway.

Tolrestat is a potent, orally active aldose reductase inhibitor with IC₅₀ of 35 nM.

Esmolol hydrochloride is an ultra-short-acting cardioselective β1-adrenergic blocker. Esmolol hydrochloride exerts its antiarrhythmic effect by activating Neurokinin 1 Receptor. Esmolol hydrochloride attenuates post resuscitation myocardial dysfunction. Esmolol hydrochloride improves diabetic wound healing by inhibiting aldose reductase and the production of advanced glycation end products and promoting fibroblast migration. Esmolol hydrochloride can be used to study cardiac diseases such as arrhythmias and diabetic foot ulcers.

Quercetin 3-gentiobioside is a flavonoid found in Artemisia iwayomogi. Quercetin 3-gentiobioside inhibits aromatase with an K_i of 46.77 nM. Quercetin 3-gentiobioside inhibits aldose reductase (AR) and the formation of advanced glycation end products (AGEs), with IC₅₀ values of 10.60 μM and 109.46 μM, respectively. Quercetin 3-gentiobioside inhibits proliferation of cancer cells and fibroblast-like synoviocytes. Quercetin 3-gentiobioside can be used for the research of cancer, such as lung carcinoma.

Soyasaponin Bb is an orally active, covalent inducer of heme oxygenase HO-1 and an inhibitor of aldose reductase AKR1B1. Soyasaponin Bb can regulate oxidative stress pathways, enhance antioxidant capacity, reduce reactive oxygen species (ROS) generation, and inhibit lipid peroxidation and hepatocyte apoptosis. Soyasaponin Bb improves alcohol-induced hepatocyte membrane damage and liver function abnormalities, and improves Scopolamine (HY-N0296)-induced memory impairment. Soyasaponin Bb has antioxidant, hepatoprotective, and neuroprotective activities.

Emodin-8-glucoside is an anthraquinone derivative that can be isolated from Aloe vera. Emodin-8-glucoside is the inhibitor for MAPK with an inhibition constant of 430.14 pM. Emodin-8-glucoside exhibits moderate inhibitory activity against rat lens aldose reductase (ALAR) and topoisomerases II with IC₅₀s of 14.4 μM and 66 μM. Emodin-8-glucoside exhibits antioxidant, anti-inflammatory and anti-fibrotic activities. Emodin-8-glucoside can cross the blood brain barrier.

Ranirestat (AS-3201) potent and orally active aldose reductase (AR) inhibitor with IC₅₀s of 11 nM and 15 nM for rat lens AR and recombinant human AR, respectively, and a K_i of 0.38 nM for recombinant human AR. Ranirestat has the potential for diabetic sensorimotor polyneuropathy treatment. Ranirestat also has a neuroprotective effect on diabetic retinas.

Zopolrestat (CP73850) is a potent, orally active aldose reductase (AR) inhibitor with an IC₅₀ of 3.1 nM. Zopolrestat is used for the research of diabetic complications.

6-Hydroxyluteolin (Compound 17) is a flavonoid derivative and also an inhibitor of Aldose reductase, with an experimental -log IC₅₀ value of 6.690. 6-Hydroxyluteolin can be isolated from the leaves of multiple plant families, including Plantaginaceae, Globulariaceae and Labiatae. 6-Hydroxyluteolin serves as a phylogenetic marker for higher plants. 6-Hydroxyluteolin can be used in the research of diabetic cataract.