U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C17H14BrN3O2S
Molecular Weight 404.2822
Optical Activity ( + / - )
Additional Stereochemistry Yes
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0
Stereo Comments AXIAL, RACEMIC

SHOW SMILES / InChI
Structure of LESINURAD

SMILES

c1ccc2c(c1)c(ccc2-n3c(Br)nnc3SCC(=O)O)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 404.2822
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
7.29999999999999982 µM [IC50]
3.70000000000000018 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
ZURAMPIC

Approved Use

INDICATIONS AND USAGE. ZURAMPIC is a URAT1 inhibitor indicated 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

Launch Date

1450742400000
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
0.303 μg/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.21 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
22 μg/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
4.02 μg/mL
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
4.74 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
7.68 μg/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
10.8 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
1.54 μg/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
6.51 μg/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
11.8 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
11.7 μg/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
17.7 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
23.1 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
21.9 μg/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.54 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
0.787 μg × h/mL
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
10.9 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
106 μg × h/mL
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
12.1 μg × h/mL
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
14.2 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
17.5 μg × h/mL
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
28.7 μg × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.12 μg × h/mL
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
30.3 μg × h/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
31.9 μg × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
33.1 μg × h/mL
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
56.4 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
70.5 μg × h/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
89.8 μg × h/mL
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
29.8 μg × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
2.73 h
5 mg single, oral
dose: 5 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
34.6 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.04 h
600 mg single, oral
dose: 600 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
10.6 h
100 mg 1 times / day multiple, oral
dose: 100 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
4.23 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
12.7 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
4.72 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.99 h
25 mg single, oral
dose: 25 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.2 h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
5.97 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
8.91 h
200 mg 1 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
5.19 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
8.91 h
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
7.48 h
400 mg 1 times / day multiple, oral
dose: 400 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FASTED
3.77 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
LESINURAD plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Doses

Doses

DosePopulationAdverse events​
1600 mg single, oral
Highest studied dose
Dose: 1600 mg
Route: oral
Route: single
Dose: 1600 mg
Sources:
healthy, mean 42 years
Health Status: healthy
Age Group: mean 42 years
Sex: M+F
Sources:
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
minor [IC50 43.1 uM]
no
no
no
weak
likely (co-administration study)
Comment: Concomitant use with lesinurad reduced the plasma concentration of sensitive CYP3A4 substrates (e.g., Sildenafil, Amlodipine), and possibly reduce the efficacy of sensitive CYP3A4 substrates
Page: 12
yes [IC50 13.7 uM]
no (co-administration study)
Comment: does not affect exposure of metformin
Page: 44
yes [IC50 148 uM]
yes [IC50 16.2 uM]
weak (co-administration study)
Comment: Coadministration with repaglinide: small increase in AUC (10-31%)
Page: 74
yes [IC50 3.5 uM]
yes [IC50 3.5 uM]
yes [IC50 384 uM]
yes [IC50 4.3 uM]
yes [IC50 40.7 uM]
weak (co-administration study)
Comment: Coadministration with tolbutamide: small increase in AUC (11%); Coadministration with OH-tolbutamide: small increase in AUC (14%)
Page: 74
yes [IC50 9.3 uM]
yes [IC50 >100 uM]
yes [IC50 >100 uM]
yes [IC50 >100 uM]
yes [IC50 >300 uM]
yes [IC50 >3000 uM]
yes [Inhibition 100 uM]
yes
yes
yes
yes
Drug as victim

Drug as victim

TargetModalityActivityMetaboliteClinical evidence
major
major
minor
minor
minor
no evidence
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
no
yes
yes
yes
yes
yes
yes (co-administration study)
Comment: Lesinurad exposure is increased by 56% when lesinurad is co-administered with fluconazole, an inhibitor of CYP2C9
Page: 70
Tox targets

Tox targets

Sample Use Guides

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
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 Sat Jun 26 13:36:28 UTC 2021
Edited
by admin
on Sat Jun 26 13:36:28 UTC 2021
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
LESINURAD [MI]
Common Name English
LESINURAD [ORANGE BOOK]
Common Name 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 Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
NDF-RT N0000192341
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C175109
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
RXCUI
1731031
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
ChEMBL
CHEMBL2105720
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
MERCK INDEX
M11920
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
DRUG BANK
DB11560
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
DRUG CENTRAL
5075
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
CAS
878672-00-5
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
EVMPD
SUB93370
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
NDF-RT
N0000190118
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY Cytochrome P450 3A Inducers [MoA]
FDA UNII
09ERP08I3W
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
NDF-RT
N0000192340
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY Urate Transporter 1 Inhibitors [MoA]
PUBCHEM
53465279
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
PRIMARY
INN
9345
Created by admin on Sat Jun 26 13:36:30 UTC 2021 , Edited by admin on Sat Jun 26 13:36:30 UTC 2021
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.
ENANTIOMER -> RACEMATE
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
ENANTIOMER -> RACEMATE
Related Record Type Details
METABOLITE -> PARENT
AMOUNT EXCRETED
FECAL
METABOLITE -> PARENT
AMOUNT EXCRETED
FECAL
METABOLITE -> PARENT
PLASMA
METABOLITE -> PARENT
AMOUNT EXCRETED
URINE
METABOLITE -> PARENT
AMOUNT EXCRETED
URINE
METABOLITE -> PARENT
PLASMA
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