Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Ranirestat
- DrugBank Accession Number
- DB05327
- Background
Ranirestat is a structurally novel and stereospecifically potent aldose reductase (AKR1B; EC 1.1.1.21) inhibitor, which contains a succinimide ring that undergoes ring-opening at physiological pH levels. It has been used in trials studying the treatment of Mild to Moderate Diabetic Sensorimotor Polyneuropathy.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
Structure for Ranirestat (DB05327)
- Weight
- Average: 420.189
Monoisotopic: 418.991696707 - Chemical Formula
- C17H11BrFN3O4
- Synonyms
- Ranirestat
- External IDs
- AS-3201
- SX 3030
- SX 3201
Pharmacology
- Indication
Investigated for use/treatment in neuropathy (diabetic).
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Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
Not Available
- Mechanism of action
Ranirestat alleviates diabetic neuropathy, a complication of diabetes, by inhibiting aldose reductase and thereby inhibiting the accumulation of intracellular sorbitol that causes diabetic neuropathy. This drug has a stronger inhibitory effect and is longer acting compared to other drugs in this therapeutic area. Ranirestat showed good penetration into the nerve tissue, resulting in dose-dependent inhibition of intraneural accumulation of sorbitol and fructose in a clinical study.
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
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
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 fluorobenzenes. These are compounds containing one or more fluorine atoms attached to a benzene ring.
- Kingdom
- Organic compounds
- Super Class
- Benzenoids
- Class
- Benzene and substituted derivatives
- Sub Class
- Halobenzenes
- Direct Parent
- Fluorobenzenes
- Alternative Parents
- Bromobenzenes / Pyrrolidine-2-ones / Aryl bromides / Aryl fluorides / N-substituted carboxylic acid imides / Pyrroles / Dicarboximides / N-unsubstituted carboxylic acid imides / Heteroaromatic compounds / Lactams show 8 more
- Substituents
- 2-pyrrolidone / Aromatic heteropolycyclic compound / Aryl bromide / Aryl fluoride / Aryl halide / Azacycle / Bromobenzene / Carbonyl group / Carboxylic acid derivative / Carboxylic acid imide show 20 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- Z26P56GFTV
- CAS number
- 147254-64-6
- InChI Key
- QCVNMNYRNIMDKV-QGZVFWFLSA-N
- InChI
- InChI=1S/C17H11BrFN3O4/c18-10-4-3-9(11(19)6-10)8-21-14(24)12-2-1-5-22(12)17(16(21)26)7-13(23)20-15(17)25/h1-6H,7-8H2,(H,20,23,25)/t17-/m1/s1
- IUPAC Name
- (3R)-2'-[(4-bromo-2-fluorophenyl)methyl]-2',3'-dihydro-1'H-spiro[pyrrolidine-3,4'-pyrrolo[1,2-a]pyrazine]-1',2,3',5-tetrone
- SMILES
- FC1=C(CN2C(=O)C3=CC=CN3[C@@]3(CC(=O)NC3=O)C2=O)C=CC(Br)=C1
References
- General References
- Bril V, Buchanan RA: Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy. Diabetes Care. 2006 Jan;29(1):68-72. [Article]
- External Links
- PubChem Compound
- 153948
- PubChem Substance
- 175426978
- ChemSpider
- 135685
- BindingDB
- 50067407
- ChEMBL
- CHEMBL334830
- ZINC
- ZINC000000598422
- Wikipedia
- Ranirestat
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Diabetic Neuropathies 1 somestatus stop reason just information to hide 2, 3 Completed Treatment Mild to Moderate Diabetic Sensorimotor Polyneuropathy 1 somestatus stop reason just information to hide
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 0.0295 mg/mL ALOGPS logP 2.3 ALOGPS logP 1.79 Chemaxon logS -4.2 ALOGPS pKa (Strongest Acidic) 9.22 Chemaxon pKa (Strongest Basic) -6.9 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 88.48 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 90.5 m3·mol-1 Chemaxon Polarizability 35.01 Å3 Chemaxon Number of Rings 4 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 + 0.9933 Blood Brain Barrier + 0.8041 Caco-2 permeable - 0.5688 P-glycoprotein substrate Substrate 0.5408 P-glycoprotein inhibitor I Inhibitor 0.5266 P-glycoprotein inhibitor II Non-inhibitor 0.8159 Renal organic cation transporter Non-inhibitor 0.6945 CYP450 2C9 substrate Non-substrate 0.8841 CYP450 2D6 substrate Non-substrate 0.7981 CYP450 3A4 substrate Substrate 0.5985 CYP450 1A2 substrate Non-inhibitor 0.6987 CYP450 2C9 inhibitor Non-inhibitor 0.6249 CYP450 2D6 inhibitor Non-inhibitor 0.8934 CYP450 2C19 inhibitor Non-inhibitor 0.5843 CYP450 3A4 inhibitor Non-inhibitor 0.629 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.744 Ames test Non AMES toxic 0.7064 Carcinogenicity Non-carcinogens 0.8581 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.4876 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9859 hERG inhibition (predictor II) Non-inhibitor 0.7574
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0000900000-564c756723bc99719558 Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-0000900000-c1ec43b85e8f88896bb2 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-014i-2000900000-72e76c6a5bc1436c475c Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-014i-0103900000-7b1c4ca5b43d06cf75f6 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0097-9022000000-902aee24361bdf60da42 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-0006-3968100000-bc154af26e499098ce35 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]- 186.0027 predictedDeepCCS 1.0 (2019) [M+H]+ 188.3607 predictedDeepCCS 1.0 (2019) [M+Na]+ 194.9286 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 November 18, 2007 18:23 / Updated at August 26, 2024 19:23