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Details

Stereochemistry ACHIRAL
Molecular Formula C17H14BrN3O2S
Molecular Weight 404.281
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LESINURAD

SMILES

OC(=O)CSC1=NN=C(Br)N1C2=C3C=CC=CC3=C(C=C2)C4CC4

InChI

InChIKey=FGQFOYHRJSUHMR-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C17H14BrN3O2S
Molecular Weight 404.281
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description

Lesinurad (brand name Zurampic) is a urate transporter inhibitor for treating hyperuricemia associated with gout in patients who have not achieved target serum uric acid levels with a xanthine oxidase inhibitor alone. In gout patients, Lesinurad lowered serum uric acid levels and increased renal clearance and fractional excretion of uric acid. Following single and multiple oral doses of Lesinurad to gout patients, dose-dependent decreases in serum uric acid levels and increases in urinary uric acid excretion were observed. Lesinurad reduces serum uric acid levels by inhibiting the function of transporter proteins involved in uric acid reabsorption in the kidney. Lesinurad inhibited the function of two apical transporters responsible for uric acid reabsorption, uric acid transporter 1 (URAT1) and organic anion transporter 4 (OAT4), with IC50 values of 7.3 and 3.7 µM, respectively. URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen. OAT4 is a uric acid transporter associated with diuretic-induced hyperuricemia. Lesinurad does not interact with the uric acid reabsorption transporter SLC2A9 (Glut9), located on the basolateral membrane of the proximal tubule cell. Based on in vitro studies, lesinurad is an inhibitor of OATP1B1, OCT1, OAT1, and OAT3; however, lesinurad is not an in vivo inhibitor of these transporters. In vivo drug interaction studies indicate that lesinurad does not decrease the renal clearance of furosemide (substrate of OAT1/3), or affect the exposure of atorvastatin (substrate of OATP1B1) or metformin (substrate of OCT1). Based on in vitro studies, lesinurad has no relevant effect on P-glycoprotein.

CNS Activity

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
3.7 µM [IC50]
7.3 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
ZURAMPIC

Sample Use Guides

In Vivo Use Guide
ZURAMPIC (Lesinurad ) is recommended at 200 mg once daily in combination with a xanthine oxidase inhibitor, including allopurinol or febuxostat. The maximum daily dose of ZURAMPIC is 200 mg.
Route of Administration: Oral
In Vitro Use Guide
OAT1 was expressed in Flp-In 293 cells. [14C]RDEA594 was incubated with cells for 5 minutes at 37C. The reaction was stopped with ice-cold transport medium and cells were lysed with 0.2 ml of 1 N NAOH and radioactivity was measured using liquid scintillation counting. There was saturable uptake of [14C]RDEA594 into oocytes expressing OAT1. The Km was 0.85 μM and Vmax was 13.0 pmol/min/mg protein
Substance Class Chemical
Created
by admin
on Mon Oct 21 21:32:40 UTC 2019
Edited
by admin
on Mon Oct 21 21:32:40 UTC 2019
Record UNII
09ERP08I3W
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LESINURAD
DASH   INN   USAN   WHO-DD  
INN   USAN  
Official Name English
LESINURAD [INN]
Common Name English
RDEA 594
Code English
RDEA594
Code English
2-((5-BROMO-4-(4-CYCLOPROPYLNAPHTHALEN-1-YL)-4H-1,2,4-TRIAZOL-3- YL)SULFANYL)ACETIC ACID
Systematic Name English
ZURAMPIC
Brand Name English
ACETIC ACID, 2-((5-BROMO-4-(4-CYCLOPROPYL-1-NAPHTHALENYL)-4H-1,2,4-TRIAZOL-3-YL)THIO)-
Common Name English
LESINURAD [USAN]
Common Name English
DUZALLO COMPONENT LESINURAD
Brand Name English
RDEA-594
Code English
LESINURAD [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-ATC M04AB05
Created by admin on Mon Oct 21 21:32:41 UTC 2019 , Edited by admin on Mon Oct 21 21:32:41 UTC 2019
NDF-RT N0000192341
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
Code System Code Type Description
RXCUI
1731031
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
PRIMARY
ChEMBL
CHEMBL2105720
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
PRIMARY
DRUG BANK
DB11560
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
PRIMARY
CAS
878672-00-5
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
PRIMARY
EVMPD
SUB93370
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
PRIMARY
NDF-RT
N0000190118
Created by admin on Mon Oct 21 21:32:41 UTC 2019 , Edited by admin on Mon Oct 21 21:32:41 UTC 2019
PRIMARY Cytochrome P450 3A Inducers [MoA]
NDF-RT
N0000192340
Created by admin on Mon Oct 21 21:32:41 UTC 2019 , Edited by admin on Mon Oct 21 21:32:41 UTC 2019
PRIMARY Urate Transporter 1 Inhibitors [MoA]
PUBCHEM
53465279
Created by admin on Mon Oct 21 21:32:41 UTC 2019 , Edited by admin on Mon Oct 21 21:32:41 UTC 2019
PRIMARY
INN
9345
Created by admin on Mon Oct 21 21:32:40 UTC 2019 , Edited by admin on Mon Oct 21 21:32:40 UTC 2019
PRIMARY
Related Record Type Details
TRANSPORTER -> INHIBITOR
Based on in vitro studies, lesinurad is a weak inhibitor of OATP1B1, OCT1, OAT1, and OAT3.
WEAK
TRANSPORTER -> NON-SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
MAJOR
METABOLIC ENZYME -> INDUCER
WEAK
TRANSPORTER -> INHIBITOR
Based on in vitro studies, lesinurad is a weak inhibitor of OATP1B1, OCT1, OAT1, and OAT3.
WEAK
METABOLIC ENZYME -> SUBSTRATE
MINOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MINOR
TRANSPORTER -> SUBSTRATE
Based on in vitro studies, lesinurad is a substrate of OAT1 and OAT3.
TRANSPORTER -> INHIBITOR
inhibits the transport of [14C]uric acid into human embryonic kidney-293 cells expressing OAT4
IC50
EXCRETED UNCHANGED
AMOUNT EXCRETED
FECAL
METABOLIC ENZYME -> SUBSTRATE
MINOR
TARGET -> INHIBITOR
inhibits the transport of [14C]uric acid into human embryonic kidney-293 cells expressing OAT4
IC50
TRANSPORTER -> INHIBITOR
Based on in vitro studies, lesinurad is a weak inhibitor of OATP1B1, OCT1, OAT1, and OAT3.
WEAK
TARGET -> INHIBITOR
inhibits the transport of [14C]uric acid into human embryonic kidney-293 cells expressing URAT1
IC50
TRANSPORTER -> SUBSTRATE
Based on in vitro studies, lesinurad is a substrate of OAT1 and OAT3.
TRANSPORTER -> INHIBITOR
Based on in vitro studies, lesinurad is a weak inhibitor of OATP1B1, OCT1, OAT1, and OAT3.
WEAK
EXCRETED UNCHANGED
AMOUNT EXCRETED
URINE
BINDER->LIGAND
BINDING
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC INTRAVENOUS ADMINISTRATION

SINGLE DOSE

Tmax PHARMACOKINETIC FED CONDITION

ORAL ADMINISTRATION