Synonym
Lesinurad sodium; Lesinurad; RDEA594; RDEA 594; RDEA-594, brand name: Zurampic.
IUPAC/Chemical Name
sodium 2-((5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H-1,2,4-triazol-3-yl)thio)acetate
InChi Key
FVYMVLTWIBGEMC-UHFFFAOYSA-M
InChi Code
InChI=1S/C17H14BrN3O2S.Na/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);/q;+1/p-1
SMILES Code
O=C(O[Na])CSC1=NN=C(Br)N1C2=C3C=CC=CC3=C(C4CC4)C=C2
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
Soluble in DMSO, not in water
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Related CAS#
1151516-14-1 ( Lesinurad sodium)
878672-00-5 ( Lesinurad free acid)
Biological target:
Lesinurad sodium -is a URAT1 and OAT inhibitor, is determined to be a substrate for the kidney transporters OAT1 and OAT3 with Km values of 0.85 and 2 µM, respectively.
In vitro activity:
Cells treated with lesinurad were indistinguishable from DMSO-treated cells and even undifferentiated controls (Fig. 5A). Of note, lesinurad exhibited no cytotoxicity up to 50 μM (data not shown) excluding that the lack of lipid accumulation is a toxic effect. To gain deeper understanding of lesinurad-mediated PPARγ modulation in adipocytes, this study analyzed their gene expression profiles after differentiation (Fig. 5B). Compared to DMSO-treated cells, the full PPARγ agonist rosiglitazone robustly induced the scavenger receptor CD36, adiponectin, fatty acid binding protein 4 (FABP4) and the glucose transporter 4 (GLUT4). In strong contrast, lesinurad at 30 μM caused almost no changes in PPARγ-regulated gene expression with only slight trends for CD36 and adiponectin induction. Thus, the gene expression profiles confirmed the results of the staining experiments and indicated that lesinurad does not activate pro-adipogenic PPARγ target gene transcription in adipocytes to cause lipid accumulation. In contrast, in human hepatoma cells (HepG2 cells), lesinurad caused a more distinguished effect on PPARγ-regulated genes (Fig. 5C). As in adipocytes, lesinurad hardly affected CD36 and adiponectin expression but markedly induced angiopoietin-like 4 (ANGPTL4).
Reference: Sci Rep. 2018; 8: 13554. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6131501/
In vivo activity:
Hyperuricemic group showed an increase in serum levels of GPT, GOT, uric acid and BUN. HU group received either ALP or ZUR (Lesinurad) showed a decrease in GPT, GOT, uric acid and BUN levels (Fig. 1a-b). Co-administration of ALP and ZUR revealed an ameliorative and additive synergistic effect (P < 0.05) on the normalization of GPT, GOT, uric acid and BUN levels (Fig. 1a). It should be noted that ZUR revealed same effect induced by ALP in hyperuricemic administered mice.
Reference: BMC Pharmacol Toxicol. 2020; 21: 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011467/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMSO |
55.5 |
137.97 |
| Ethanol |
85.0 |
199.41 |
| Water |
8.0 |
18.77 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
426.26
Batch specific molecular weights may vary
from batch to batch
due to the degree of hydration, which will
affect the solvent
volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass |
1 mg |
5 mg |
10 mg |
| 1 mM |
1.15 mL |
5.76 mL |
11.51 mL |
| 5 mM |
0.23 mL |
1.15 mL |
2.3 mL |
| 10 mM |
0.12 mL |
0.58 mL |
1.15 mL |
| 50 mM |
0.02 mL |
0.12 mL |
0.23 mL |
Formulation protocol:
1. Heitel P, Gellrich L, Heering J, Goebel T, Kahnt A, Proschak E, Schubert-Zsilavecz M, Merk D. Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro. Sci Rep. 2018 Sep 10;8(1):13554. doi: 10.1038/s41598-018-31833-4. PMID: 30202096; PMCID: PMC6131501.
2. Alghamdi YS, Soliman MM, Nassan MA. Impact of Lesinurad and allopurinol on experimental Hyperuricemia in mice: biochemical, molecular and Immunohistochemical study. BMC Pharmacol Toxicol. 2020 Feb 10;21(1):10. doi: 10.1186/s40360-020-0386-7. PMID: 32041665; PMCID: PMC7011467.
In vitro protocol:
1. Heitel P, Gellrich L, Heering J, Goebel T, Kahnt A, Proschak E, Schubert-Zsilavecz M, Merk D. Urate transporter inhibitor lesinurad is a selective peroxisome proliferator-activated receptor gamma modulator (sPPARγM) in vitro. Sci Rep. 2018 Sep 10;8(1):13554. doi: 10.1038/s41598-018-31833-4. PMID: 30202096; PMCID: PMC6131501.
In vivo protocol:
1. Alghamdi YS, Soliman MM, Nassan MA. Impact of Lesinurad and allopurinol on experimental Hyperuricemia in mice: biochemical, molecular and Immunohistochemical study. BMC Pharmacol Toxicol. 2020 Feb 10;21(1):10. doi: 10.1186/s40360-020-0386-7. PMID: 32041665; PMCID: PMC7011467.
1: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK547982/ PubMed PMID: 31643315.
2: Pérez-Ruiz F, Jansen T, Tausche AK, Juárez-Campo M, Gurunath RK, Richette P. Efficacy and safety of lesinurad for the treatment of hyperuricemia in gout. Drugs Context. 2019 May 29;8:212581. doi: 10.7573/dic.212581. eCollection 2019. Review. PubMed PMID: 31191704; PubMed Central PMCID: PMC6544139.
3: Dean L. Lesinurad Therapy and CYP2C9 Genotype. 2019 Feb 11. In: Pratt V, McLeod H, Rubinstein W, Dean L, Kattman B, Malheiro A, editors. Medical Genetics Summaries [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2012-. Available from http://www.ncbi.nlm.nih.gov/books/NBK537366/ PubMed PMID: 30742400.
4: Jansen TL, Perez-Ruiz F, Tausche AK, Richette P. International position paper on the appropriate use of uricosurics with the introduction of lesinurad. Clin Rheumatol. 2018 Dec;37(12):3159-3165. doi: 10.1007/s10067-018-4306-9. Epub 2018 Sep 22. Review. PubMed PMID: 30244431.
5: Claus LW, Saseen JJ. Patient considerations in the management of gout and role of combination treatment with lesinurad. Patient Relat Outcome Meas. 2018 Jul 18;9:231-238. doi: 10.2147/PROM.S108868. eCollection 2018. Review. PubMed PMID: 30140163; PubMed Central PMCID: PMC6054769.
6: On PC. Lesinurad (Zurampic) for Gout. Am Fam Physician. 2018 Mar 15;97(6):374-375. Review. PubMed PMID: 29671542.
7: Haber SL, Fente G, Fenton SN, Walker EP, Weaver BM, Cano AJ, Vu K. Lesinurad: A Novel Agent for Management of Chronic Gout. Ann Pharmacother. 2018 Jul;52(7):690-696. doi: 10.1177/1060028018762103. Epub 2018 Feb 26. Review. PubMed PMID: 29482353.
8: Jones G, Panova E, Day R. Guideline development for the management of gout: role of combination therapy with a focus on lesinurad. Drug Des Devel Ther. 2017 Oct 24;11:3077-3081. doi: 10.2147/DDDT.S97959. eCollection 2017. Review. Erratum in: Drug Des Devel Ther. 2017 Dec 15;11:3589-3590. PubMed PMID: 29123379; PubMed Central PMCID: PMC5661481.
9: Deeks ED. Lesinurad: A Review in Hyperuricaemia of Gout. Drugs Aging. 2017 May;34(5):401-410. doi: 10.1007/s40266-017-0461-y. Review. PubMed PMID: 28425024.
10: Gupta A, Sharma PK, Misra AK, Singh S. Lesinurad: A significant advancement or just another addition to existing therapies of gout? J Pharmacol Pharmacother. 2016 Oct-Dec;7(4):155-158. doi: 10.4103/0976-500X.195897. Review. PubMed PMID: 28163535; PubMed Central PMCID: PMC5242027.
11: Lesinurad (Zurampic) for gout-associated hyperuricemia. Med Lett Drugs Ther. 2016 Nov 21;58(1508):148-150. Review. PubMed PMID: 27849193.
12: Hoy SM. Lesinurad: First Global Approval. Drugs. 2016 Mar;76(4):509-16. doi: 10.1007/s40265-016-0550-y. Review. PubMed PMID: 26861027.
