Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Zenarestat
- DrugBank Accession Number
- DB02132
- Background
Not Available
- Type
- Small Molecule
- Groups
- Experimental
- Structure
Structure for Zenarestat (DB02132)
- Weight
- Average: 441.636
Monoisotopic: 439.957475409 - Chemical Formula
- C17H11BrClFN2O4
- Synonyms
- Zenarestat
Pharmacology
- Indication
Investigated for use/treatment in neuropathy (diabetic).
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Not Available
- Mechanism of action
Polyneuropathy, damage of peripheral neurons, is common in diabetes mellitus patients and causes pain, sensory and motor deficits in the limbs. Zenarestat is an aldose reductase inhibitor which inhibits the metabolism of glucose by the polyol pathway, which possibly slows or reduces progression of polyneuropathy. Chronic hyperglycemia affects peripheral nerves by an extracellular mechanism with many types of glycation reactions and chemical rearrangements, and an intracellular route involving increased amounts of glucose passing through the polyol pathway. The polyol pathway allows cells to produce fructose from glucose, and has two steps, which require energy and enzymes. Aldose reductase catalyzes the conversion of glucose to sorbitol in the first step, while the second involves the oxidation of nicotinamide adenine dicnucleotide phosphate (conversion of NADPH to NADP). Chronic hyperglycemia causes damage by overactivity of the polyol pathway, causing a decrease in cellular NADPH levels, reducing the amount of glutathione (a free radical scavenger), and nitric oxide (a vasodilator), as well as increasing cellular sorbital levels, causing decreased levels of myo-inositol (necessary for Na-K ATPase function) and increased fructose, thus increasing AGE (advanced glycosylation end products), the byproduct of the polyol pathway. The suppression of the first step in the polyol pathway by zenarestat prevents these deleterious processes from occuring.
Target Actions Organism AAldo-keto reductase family 1 member B1 inhibitorHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as quinazolines. These are compounds containing a quinazoline moiety, which is made up of two fused six-member aromatic rings, a benzene ring and a pyrimidine ring.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Diazanaphthalenes
- Sub Class
- Benzodiazines
- Direct Parent
- Quinazolines
- Alternative Parents
- Alpha amino acids and derivatives / Pyrimidones / Bromobenzenes / Fluorobenzenes / Aryl bromides / Aryl chlorides / Aryl fluorides / Vinylogous amides / Heteroaromatic compounds / Ureas show 12 more
- Substituents
- Alpha-amino acid or derivatives / Aromatic heteropolycyclic compound / Aryl bromide / Aryl chloride / Aryl fluoride / Aryl halide / Azacycle / Benzenoid / Bromobenzene / Carbonyl group show 24 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 180C9PJ8JT
- CAS number
- 112733-06-9
- InChI Key
- SXONDGSPUVNZLO-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H11BrClFN2O4/c18-10-2-1-9(13(20)5-10)7-22-16(25)12-4-3-11(19)6-14(12)21(17(22)26)8-15(23)24/h1-6H,7-8H2,(H,23,24)
- IUPAC Name
- 2-{3-[(4-bromo-2-fluorophenyl)methyl]-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-yl}acetic acid
- SMILES
- OC(=O)CN1C(=O)N(CC2=C(F)C=C(Br)C=C2)C(=O)C2=C1C=C(Cl)C=C2
References
- General References
- Chalk C, Benstead TJ, Moore F: Aldose reductase inhibitors for the treatment of diabetic polyneuropathy. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD004572. [Article]
- External Links
- PubChem Compound
- 5724
- PubChem Substance
- 46507491
- ChemSpider
- 5522
- BindingDB
- 16496
- ChEMBL
- CHEMBL10413
- ZINC
- ZINC000000596737
- PDBe Ligand
- ZES
- Wikipedia
- Zenarestat
- PDB Entries
- 1iei
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.0101 mg/mL ALOGPS logP 3.26 ALOGPS logP 3.55 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 3.41 Chemaxon pKa (Strongest Basic) -7.4 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 77.92 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 95.13 m3·mol-1 Chemaxon Polarizability 36.5 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9661 Blood Brain Barrier + 0.7479 Caco-2 permeable - 0.5579 P-glycoprotein substrate Non-substrate 0.657 P-glycoprotein inhibitor I Non-inhibitor 0.8388 P-glycoprotein inhibitor II Non-inhibitor 0.8866 Renal organic cation transporter Non-inhibitor 0.8342 CYP450 2C9 substrate Non-substrate 0.7536 CYP450 2D6 substrate Non-substrate 0.8291 CYP450 3A4 substrate Non-substrate 0.5775 CYP450 1A2 substrate Non-inhibitor 0.5 CYP450 2C9 inhibitor Non-inhibitor 0.7337 CYP450 2D6 inhibitor Non-inhibitor 0.9414 CYP450 2C19 inhibitor Non-inhibitor 0.712 CYP450 3A4 inhibitor Non-inhibitor 0.6862 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.6255 Ames test Non AMES toxic 0.7627 Carcinogenicity Non-carcinogens 0.8469 Biodegradation Not ready biodegradable 0.9956 Rat acute toxicity 2.0485 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.8802 hERG inhibition (predictor II) Non-inhibitor 0.8317
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0000900000-e72ec0dac2cd6cf8ae87 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-01q0-1611900000-309b4327a5315edd383d Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-0002900000-2556986290d24a1b0a0f Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-00ku-0619000000-0c919b9715908ea055e7 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-000l-4309800000-6258cf6f01d94b1d71b7 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9213000000-3456ae802d8f0c4cc5d6 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 184.4620561 predictedDarkChem Lite v0.1.0 [M-H]- 181.06065 predictedDeepCCS 1.0 (2019) [M+H]+ 184.6240561 predictedDarkChem Lite v0.1.0 [M+H]+ 183.41866 predictedDeepCCS 1.0 (2019) [M+Na]+ 185.0507561 predictedDarkChem Lite v0.1.0 [M+Na]+ 190.44603 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols. Displays enzymatic activity towards endogenous metabolites such as aromatic and aliphatic aldehydes, ketones, monosacharides, bile acids and xenobiotics substrates. Key enzyme in the polyol pathway, catalyzes reduction of glucose to sorbitol during hyperglycemia (PubMed:1936586). Reduces steroids and their derivatives and prostaglandins. Displays low enzymatic activity toward all-trans-retinal, 9-cis-retinal, and 13-cis-retinal (PubMed:12732097, PubMed:19010934, PubMed:8343525). Catalyzes the reduction of diverse phospholipid aldehydes such as 1-palmitoyl-2-(5-oxovaleroyl)-sn -glycero-3-phosphoethanolamin (POVPC) and related phospholipid aldehydes that are generated from the oxydation of phosphotidylcholine and phosphatdyleethanolamides (PubMed:17381426). Plays a role in detoxifying dietary and lipid-derived unsaturated carbonyls, such as crotonaldehyde, 4-hydroxynonenal, trans-2-hexenal, trans-2,4-hexadienal and their glutathione-conjugates carbonyls (GS-carbonyls) (PubMed:21329684)
- Specific Function
- Aldose reductase (nadph) activity
- Gene Name
- AKR1B1
- Uniprot ID
- P15121
- Uniprot Name
- Aldo-keto reductase family 1 member B1
- Molecular Weight
- 35853.125 Da
References
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:22