LESINURAD

US Previously Marketed

First approved in 2015

Details

Stereochemistry	RACEMIC
Molecular Formula	C17H14BrN3O2S
Molecular Weight	404.281
Optical Activity	( + / - )
Additional Stereochemistry	Yes
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0
Stereo Comments	AXIAL, RACEMIC

SHOW SMILES / InChI

Structure Search

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

Description
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf

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

Primary Target	Pharmacology	Condition	Potency
Solute carrier family 22 member 12 10 Target ID: CHEMBL6120 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf	Inhibitor 8297		7.3 µM [IC50]
Solute carrier family 22 member 11 12 Target ID: CHEMBL2073677 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf	Inhibitor 8297		3.7 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Hyperuricemia 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf	Secondary		Approved 8429	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 2015

C_max

Value	Dose	Analyte	Population
0.303 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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

Value	Dose	Analyte	Population
0.787 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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

T_1/2

Value	Dose	Analyte	Population
2.73 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26170627/	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

Dose	Population	Adverse events
1600 mg single, oral Highest studied dose Dose: 1600 mg Route: oral Route: single Dose: 1600 mg Sources: https://pubmed.ncbi.nlm.nih.gov/27826183/	healthy, mean 42 years n = 10 Health Status: healthy Age Group: mean 42 years Sex: M+F Population Size: 10 Sources: https://pubmed.ncbi.nlm.nih.gov/27826183/	Sources: https://pubmed.ncbi.nlm.nih.gov/27826183/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1037 inducer 389 inhibitor 1767	substrate 1217 inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2C8 911 CYP2C19 1478 CYP2B6 810 UGT1A1 204 UGT2B7 146 OAT1 599 OAT3 642 OAT4 146 MATE1 306 MATE2 263 OATP1B1 788 OATP1B3 706 BCRP 699 OCT1 512 OCT2 647	CYP3A 191 CYP1A2 1054 CYP2A6 543 CYP1B1 92 CYP2B6 664 CYP2C8 693 CYP2E1 667 CYP2J2 56 OAT1 326 OAT3 339 UGT1A1 418 UGT1A3 422 UGT1A4 347 UGT1A6 307 UGT1A7 236 UGT1A8 283 UGT1A9 380 UGT1A10 291 UGT2B4 249 UGT2B7 389 UGT2B15 203 UGT2B17 213 P-gp 1537 BCRP 561 OCT1 327 OCT2 355 CYP1A1 349 CYP2C19 991	CYP3A 129 CYP1A2 701 CYP2C8 168 CYP2B6 547 CYP2C19 293

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	minor [IC50 43.1 uM]
CYP1A2 1692	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf#page=12 Page: 12.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
MATE2 263	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=48 Page: 48.0	no
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf#page=12 Page: 12.0	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 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207988lbl.pdf#page=12 Page: 12.0
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	yes [IC50 13.7 uM]	no (co-administration study) Comment: does not affect exposure of metformin Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0
UGT1A1 254	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=76 Page: 76.0	yes [IC50 148 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0	yes [IC50 16.2 uM]	weak (co-administration study) Comment: Coadministration with repaglinide: small increase in AUC (10-31%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0
OAT4 146	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11 Page: 11.0	yes [IC50 3.5 uM]
OAT3 644	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=6#page=47 Page: 11.0	yes [IC50 3.5 uM]	no (co-administration study) Comment: does not affect renal clearance of furosemide Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=6#page=47 Page: 11.0
UGT2B7 157	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=76 Page: 76.0	yes [IC50 384 uM]
OAT1 603	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=6#page=47 Page: 11.0	yes [IC50 4.3 uM]	no (co-administration study) Comment: does not affect renal clearance of furosemide Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=11;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=6#page=47 Page: 11.0
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0	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%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	yes [IC50 9.3 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0	yes [IC50 >100 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0	yes [IC50 >100 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=74 Page: 74.0	yes [IC50 >100 uM]
OCT2 648	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	yes [IC50 >300 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	yes [IC50 >3000 uM]
MATE1 308	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=48 Page: 48.0	yes [Inhibition 100 uM]
CYP2B6 1001	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=77 Page: 77.0	yes
CYP2C19 1553	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=77 Page: 77.0	yes
CYP2C8 965	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=77 Page: 77.0	yes
CYP2C9 1819	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=77 Page: 77.0	yes

Drug as victim

Target	Modality	Activity	Clinical evidence
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	major
UGT2B7 389	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	major
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	minor
CYP1A1 349	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=43 Page: 43.0	minor
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=43 Page: 43.0	minor
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=187 Page: 187.0	no evidence
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP1B1 92	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP2B6 664	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP2C8 693	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
CYP2J2 56	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=72 Page: 72.0	no
OCT2 355	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44;47	no
UGT1A10 291	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT1A3 422	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT1A4 347	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT1A6 307	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT1A7 236	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT1A8 283	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT1A9 380	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT2B15 203	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT2B17 213	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
UGT2B4 249	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=75 Page: 75.0	no
CYP3A 191	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=70 Page: 70.0	yes
OAT1 326	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=42 Page: 42.0	yes
OAT3 339	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=42 Page: 42.0	yes
OCT1 327	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=44 Page: 44.0	yes
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=70;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=6 Page: 70.0	yes	yes (co-administration study) Comment: Lesinurad exposure is increased by 56% when lesinurad is co-administered with fluconazole, an inhibitor of CYP2C9 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=70;https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000ClinPharmR.pdf#page=6 Page: 70.0

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2015/207988Orig1s000PharmR.pdf#page=152 Page: 152.0

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:90929	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:90929
ChemicalBook	CB32628032	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB32628032
MolPort	MolPort-039-138-666	https://www.molport.com/shop/molecule-link/MolPort-039-138-666
ZINC	ZINC000084757007	http://zinc15.docking.org/substances/ZINC000084757007

PubMed

Title	Date	PubMed
Gout therapeutics: new drugs for an old disease.	2011 Jan 8	20719377

Patents

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

Name

Type

Language

LESINURAD

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