Identification
- Summary
Lesinurad is a uric acid 1 transporter inhibitor typically used in combination with a xanthine oxidase inhibitor to treat hyperuricemia associated with gout in patients with inadequate control of uric acid levels with xanthine oxidase inhibitor monotherapy.
- Generic Name
- Lesinurad
- DrugBank Accession Number
- DB11560
- Background
Lesinurad is an oral uric acid transporter 1 (URAT1) inhibitor indicated for the treatment of hyperuricemia associated with gout. It reduces serum uric acid concentration through the inhibition of URAT1, an enzyme responsible for reuptake of uric acid from the renal tubule, and OAT4, another uric acid transporter associated with diuretic-induced hyperuricemia.
Marketed as the product Zurampic, it is indicated for use in combination with a xanthine oxidase inhibitor for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. In August 2017, a combination oral therapy consisting of lesinurad and Allopurinol was FDA-approved under the brand name Duzallo indicated for the treatment of gout-related hyperuricemia in patients with uncontrolled gout.
- Type
- Small Molecule
- Groups
- Approved, Investigational
- Structure
Structure for Lesinurad (DB11560)
- Weight
- Average: 404.28
Monoisotopic: 402.999011 - Chemical Formula
- C17H14BrN3O2S
- Synonyms
- {[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid
- Lesinurad
- External IDs
- RDEA 594
- RDEA-594
- RDEA594
Pharmacology
- Indication
For use, in combination with a xanthine oxidase inhibitor, for the treatment of hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone.
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Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Used in combination to treat Hyperuricemia •••••••••••• - Contraindications & Blackbox Warnings
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Dose-dependent reductions in serum uric acid levels and increases in urinary uric acid excretion have been observed following single and multiple oral doses of lesinurad.
- Mechanism of action
Lesinurad inhibits the activity of uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4). URAT1 is a major transporter enzyme responsible for reuptake of uric acid from the renal tubules; inhibition of URAT1 function thereby increases excretion of uric acid.
Target Actions Organism ASolute carrier family 22 member 12 inhibitorHumans ASolute carrier family 22 member 11 inhibitorHumans - Absorption
Oral lesinurad is rapidly absorbed, reaching maximum plasma concentrations (Cmax) within 1–4 h following the administration a single 200 mg dose (in either the fed or fasted state).
- Volume of distribution
The mean steady state volume of distribution of lesinurad was approximately 20 L following intravenous dosing.
- Protein binding
Lesinurad is extensively bound to proteins in plasma (greater than 98%), mainly to albumin.
- Metabolism
Lesinurad undergoes oxidative metabolism mainly via the polymorphic cytochrome P450 CYP2C9 enzyme.
- Route of elimination
Within 7 days following single dosing of radiolabeled lesinurad, 63% of administered radioactive dose was recovered in urine and 32% of administered radioactive dose was recovered in feces. Most of the radioactivity recovered in urine (> 60% of dose) occurred in the first 24 hours. Unchanged lesinurad in urine accounted for approximately 30% of the dose.
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
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Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C9 CYP2C9*2 Not Available 430C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*3 Not Available 1075A>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*4 Not Available 1076T>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*5 Not Available 1080C>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*8 Not Available 449G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*11 Not Available 1003C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*12 Not Available 1465C>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*13 Not Available 269T>C Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*14 Not Available 374G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*16 Not Available 895A>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*18 Not Available 1075A>C / 1190A>C … show all Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*26 Not Available 389C>G Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*28 Not Available 641A>T Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*30 Not Available 1429G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*33 Not Available 395G>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*6 Not Available 818delA Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*15 Not Available 485C>A Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*25 Not Available 353_362delAGAAATGGAA Effect Inferred Poor drug metabolizer. Details Cytochrome P450 2C9 CYP2C9*35 Not Available 374G>T / 430C>T Effect Inferred Poor drug metabolizer. Details
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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbacavir Abacavir may decrease the excretion rate of Lesinurad which could result in a higher serum level. Abatacept The metabolism of Lesinurad can be increased when combined with Abatacept. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Lesinurad. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Lesinurad. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Lesinurad. - Food Interactions
- Drink plenty of fluids.
- Take with a full glass of water.
- Take with food.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Zurampic Tablet, film coated 200 mg Oral Grunenthal Gmb H 2016-09-08 2020-07-31 EU 
Zurampic Tablet, film coated 200 mg/1 Oral Ironwood Pharmaceuticals, Inc. 2017-10-03 2020-07-31 US 
Zurampic Tablet, film coated 200 mg Oral Grunenthal Gmb H 2016-09-08 2020-07-31 EU Zurampic Tablet, film coated 200 mg Oral Grunenthal Gmb H 2016-09-08 2020-07-31 EU Zurampic Tablet, film coated 200 mg Oral Grunenthal Gmb H 2016-09-08 2020-07-31 EU - Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image DUZALLO Lesinurad (200 MG) + Allopurinol (200 MG) Tablet, film coated Oral Grunenthal Gmbh 2019-01-29 2020-08-28 Italy 
Duzallo Lesinurad (200 mg/1) + Allopurinol (200 mg/1) Tablet, film coated Oral Ironwood Pharmaceuticals, Inc. 2017-10-03 2020-04-30 US DUZALLO Lesinurad (200 MG) + Allopurinol (300 MG) Tablet, film coated Oral Grunenthal Gmbh 2019-01-29 2020-08-28 Italy DUZALLO Lesinurad (200 MG) + Allopurinol (200 MG) Tablet, film coated Oral Grunenthal Gmbh 2019-01-29 2020-08-28 Italy DUZALLO Lesinurad (200 MG) + Allopurinol (300 MG) Tablet, film coated Oral Grunenthal Gmbh 2019-01-29 2020-08-28 Italy
Categories
- ATC Codes
- M04AB05 — Lesinurad
- Drug Categories
- Acetates
- Acids, Acyclic
- Antigout Preparations
- Antirheumatic Agents
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (weak)
- Cytochrome P-450 Enzyme Inducers
- Cytochrome P-450 Substrates
- Drugs that are Mainly Renally Excreted
- Musculo-Skeletal System
- Preparations Increasing Uric Acid Excretion
- Sulfhydryl Compounds
- Sulfur Compounds
- Urate Transporter 1 Inhibitor
- Urate Transporter 1 Inhibitors
- Uricosuric Agents
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenyl-1,2,4-triazoles. These are organic compounds containing a 1,2,4-triazole substituted by a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azoles
- Sub Class
- Triazoles
- Direct Parent
- Phenyl-1,2,4-triazoles
- Alternative Parents
- Naphthalenes / Alkylarylthioethers / Aryl bromides / Heteroaromatic compounds / Sulfenyl compounds / Monocarboxylic acids and derivatives / Carboxylic acids / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds show 4 more
- Substituents
- Alkylarylthioether / Aromatic heteropolycyclic compound / Aryl bromide / Aryl halide / Aryl thioether / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid / Carboxylic acid derivative show 16 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 09ERP08I3W
- CAS number
- 878672-00-5
- InChI Key
- FGQFOYHRJSUHMR-UHFFFAOYSA-N
- InChI
- InChI=1S/C17H14BrN3O2S/c18-16-19-20-17(24-9-15(22)23)21(16)14-8-7-11(10-5-6-10)12-3-1-2-4-13(12)14/h1-4,7-8,10H,5-6,9H2,(H,22,23)
- IUPAC Name
- 2-{[5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl]sulfanyl}acetic acid
- SMILES
- OC(=O)CSC1=NN=C(Br)N1C1=CC=C(C2CC2)C2=C1C=CC=C2
References
- General References
- Hoy SM: Lesinurad: First Global Approval. Drugs. 2016 Mar;76(4):509-16. doi: 10.1007/s40265-016-0550-y. [Article]
- External Links
- KEGG Drug
- D09921
- PubChem Compound
- 53465279
- PubChem Substance
- 347827983
- ChemSpider
- 28527877
- BindingDB
- 37953
- 1731031
- ChEBI
- 90929
- ChEMBL
- CHEMBL2105720
- ZINC
- ZINC000084757007
- PharmGKB
- PA166160006
- RxList
- RxList Drug Page
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Lesinurad
- FDA label
- Download (642 KB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Terminated Treatment Chronic Kidney Disease (CKD) / Gout Flares 1 3 Completed Treatment Gout Flares 6 3 Completed Treatment Tophaceous Gout 1 2 Completed Treatment Gout Flares 1 2 Completed Treatment Hyperuricemia 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Tablet, film coated Oral Tablet, film coated Oral 200 MG Tablet, film coated Oral 200 mg/1 - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US8283369 No 2012-10-09 2028-11-26 US US8084483 No 2011-12-27 2029-08-17 US US8357713 No 2013-01-22 2028-11-26 US US8546437 No 2013-10-01 2029-04-29 US US9216179 No 2015-12-22 2030-08-02 US US8003681 No 2011-08-23 2025-08-25 US US8546436 No 2013-10-01 2032-02-29 US US9956205 No 2018-05-01 2031-12-28 US US10183012 No 2019-01-22 2028-11-26 US
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00779 mg/mL ALOGPS logP 3.42 ALOGPS logP 4.09 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 3.13 Chemaxon pKa (Strongest Basic) -0.05 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 4 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 68.01 Å2 Chemaxon Rotatable Bond Count 4 Chemaxon Refractivity 109.15 m3·mol-1 Chemaxon Polarizability 36.59 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
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0002900000-f25a996db0d2ca2d125f Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-0udi-0005900000-73e1dbede218097ae55d Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-003u-2191100000-44c739ff508852f56a26 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-03xu-3329100000-9ae553d0d118913df902 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-0005-9010000000-4df16935a1b9d11bfba0 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-004i-9100000000-b105c89480bce73417f0 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]- 170.12802 predictedDeepCCS 1.0 (2019) [M+H]+ 172.48601 predictedDeepCCS 1.0 (2019) [M+Na]+ 178.79144 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Urate transmembrane transporter activity
- Specific Function
- Required for efficient urate re-absorption in the kidney. Regulates blood urate levels. Mediates saturable urate uptake by facilitating the exchange of urate against organic anions.
- Gene Name
- SLC22A12
- Uniprot ID
- Q96S37
- Uniprot Name
- Solute carrier family 22 member 12
- Molecular Weight
- 59629.57 Da
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Sodium-independent organic anion transmembrane transporter activity
- Specific Function
- Mediates saturable uptake of estrone sulfate, dehydroepiandrosterone sulfate and related compounds.
- Gene Name
- SLC22A11
- Uniprot ID
- Q9NSA0
- Uniprot Name
- Solute carrier family 22 member 11
- Molecular Weight
- 59970.945 Da
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Lesinurad FDA Label [File]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- CYP3A4
- Uniprot ID
- P08684
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
References
- Gillen M, Yang C, Wilson D, Valdez S, Lee C, Kerr B, Shen Z: Evaluation of Pharmacokinetic Interactions Between Lesinurad, a New Selective Urate Reabsorption Inhibitor, and CYP Enzyme Substrates Sildenafil, Amlodipine, Tolbutamide, and Repaglinide. Clin Pharmacol Drug Dev. 2017 Jul;6(4):363-376. doi: 10.1002/cpdd.324. Epub 2017 Jan 9. [Article]
- Lesinurad FDA label [Link]
Drug created at March 10, 2016 03:25 / Updated at February 21, 2021 18:53