| Size | Price | Stock | Qty |
|---|---|---|---|
| 50mg |
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| Other Sizes |
| Targets |
URAT1[1]
Ruzinurad specifically targets the urate transporter 1 (URAT1), which is localized to the apical membrane of renal proximal tubule epithelial cells. URAT1 is the major urate reabsorption transporter in the kidney, responsible for reabsorbing approximately 90% of filtered uric acid back into the bloodstream. Ruzinurad acts as a highly selective and potent inhibitor of URAT1. By blocking URAT1, it inhibits uric acid reabsorption, promotes urinary uric acid excretion, and reduces serum uric acid (sUA) levels. |
|---|---|
| ln Vitro |
Ruzinurad is an extremely effective inhibitor of URATl [1].
In vitro, Ruzinurad is a highly selective URAT1 inhibitor with an IC50 of 34.79 nM for human URAT1 activity. It demonstrates significant activity in reducing serum urate levels in preclinical models. Ruzinurad is superior to Lesinurad in decreasing serum uric acid levels. It is a potent, highly selective, and orally available urate transporter 1 (URAT1) inhibitor. |
| ln Vivo |
In vivo, Ruzinurad has shown robust sUA lowering effect in patients with hyperuricemia and gout. In a Phase 3 clinical study, Ruzinurad demonstrated superior sUA lowering effect over allopurinol, along with a well-tolerated safety profile, in patients with hyperuricemia associated with primary gout. It has also been studied in combination with febuxostat in patients with an inadequate response to febuxostat alone. Ruzinurad (SHR4640) is the first domestically developed URAT1 inhibitor for the long-term treatment of primary gout with hyperuricemia.
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| Enzyme Assay |
The specific protocol for URAT1 binding inhibition uses an in vitro [14C]-urate uptake assay in URAT1-expressing cells. HEK-293 cells or oocytes stably expressing human URAT1 are seeded in 24-well plates. Cells are pre-incubated with Ruzinurad (0.1-1000 nM) for 15 minutes at 37degC. [14C]-uric acid (50 uM, 1 uCi) is added and incubation is continued for 30 minutes. Cells are washed three times with ice-cold sodium-free buffer, lysed with 0.2 N NaOH, and radioactivity is measured by liquid scintillation counting. The IC50 (34.79 nM) is calculated from the concentration-response curve using non-linear regression analysis. Potassium oxonate is used as a positive control for URAT1 inhibition.
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| Cell Assay |
For in vitro cellular assays, human renal proximal tubule epithelial cells (RPTEC) are cultured in 24-well plates. Cells are treated with Ruzinurad (0.01-1000 nM) for 24 hours. After treatment, culture medium is collected and uric acid levels are measured using a commercial uric acid assay kit (enzymatic colorimetric method). Intracellular uric acid accumulation is also measured. The ability of Ruzinurad to inhibit uric acid reabsorption and promote uric acid excretion is quantified by the reduction in intracellular uric acid levels or the increase in uric acid in the culture medium.
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| Animal Protocol |
An in vivo protocol for Ruzinurad uses a hyperuricemic mouse model induced by potassium oxonate. Male ICR mice (6-8 weeks old, 20-25 g) are injected intraperitoneally with potassium oxonate (250 mg/kg) to inhibit uricase and induce hyperuricemia. Ruzinurad is administered orally by gavage at doses of 0.3, 1, 3, and 10 mg/kg (formulated in 0.5% methylcellulose) 1 hour after potassium oxonate injection. Blood samples are collected from the retro-orbital sinus at 1, 2, 4, and 6 hours post-administration. Serum uric acid (sUA) levels are measured using a commercial uric acid assay kit. The percent reduction in sUA is calculated relative to the hyperuricemic control group. The ED50 for sUA reduction is determined from dose-response curves.
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| ADME/Pharmacokinetics |
Ruzinurad has been evaluated in human clinical studies. An NDA (New Drug Application) for the long-term treatment of primary gout with hyperuricemia was submitted to the China NMPA in January 2025. A 12-week, multicenter, randomized, double-blind, placebo-controlled Phase 2 study of Ruzinurad in combination with febuxostat has been completed for primary gout and hyperuricemia with an inadequate response to febuxostat alone. A Phase 3 study comparing Ruzinurad to allopurinol in patients with hyperuricemia associated with primary gout has also been conducted. The drug has been well-tolerated and shows robust sUA lowering effect.
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| Toxicity/Toxicokinetics |
Specific toxicity data for Ruzinurad is not available. In clinical studies, Ruzinurad has been well-tolerated. Common adverse effects of URAT1 inhibitors may include gastrointestinal disturbances (diarrhea, nausea), headache, and rash. Rare but serious adverse events include renal stones due to increased uric acid excretion and potential hepatotoxicity. Standard safety assessment would include monitoring of liver function tests, renal function, and urinalysis. As a highly selective URAT1 inhibitor, Ruzinurad is designed to minimize off-target effects compared to non-specific uricosurics like probenecid.
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| References | |
| Additional Infomation |
Ruzinurad is being studied in the clinical trial NCT04956432 (a multicenter, randomized, double-blind, allopurinol-controlled study designed to evaluate the efficacy and safety of SHR4640 in patients with gout).
Ruzinurad (SHR4640) is an investigational drug and has not received full regulatory approval for clinical use. Its NDA has been submitted to the China NMPA for the long-term treatment of primary gout with hyperuricemia. Its molecular formula is C14H12BrNO2S with a molecular weight of 338.22. Ruzinurad is a highly selective and potent URAT1 inhibitor (IC50 = 34.79 nM) that is orally available and significantly decreases serum uric acid levels superior to Lesinurad. It is the first domestically developed URAT1 inhibitor in China and represents a new class of uricosuric agents for the treatment of gout and hyperuricemia. |
| Molecular Formula |
C14H12BRNO2S
|
|---|---|
| Molecular Weight |
338.22
|
| Exact Mass |
336.977
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| CAS # |
1638327-48-6
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| PubChem CID |
86294127
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| Appearance |
White to off-white solid powder
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| Density |
1.7±0.1 g/cm3
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| Boiling Point |
528.9±40.0 °C at 760 mmHg
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| Flash Point |
273.7±27.3 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
|
| Index of Refraction |
1.730
|
| LogP |
3.12
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| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
3
|
| Heavy Atom Count |
19
|
| Complexity |
361
|
| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CC(C1)(C(=O)O)SC2=C3C=C(C=CC3=NC=C2)Br
|
| InChi Key |
QGBWIYLNOBYNDL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H12BrNO2S/c15-9-2-3-11-10(8-9)12(4-7-16-11)19-14(13(17)18)5-1-6-14/h2-4,7-8H,1,5-6H2,(H,17,18)
|
| Chemical Name |
1-(6-bromoquinolin-4-yl)sulfanylcyclobutane-1-carboxylic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 33.33 mg/mL (98.55 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.9567 mL | 14.7833 mL | 29.5666 mL | |
| 5 mM | 0.5913 mL | 2.9567 mL | 5.9133 mL | |
| 10 mM | 0.2957 mL | 1.4783 mL | 2.9567 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Link: https://clinicaltrials.gov/ct2/show/NCT07362355
Conditions:Primary Gout and HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT04956432
Conditions:GoutLink: https://clinicaltrials.gov/ct2/show/NCT05954169
Conditions:Hyperuricemia
Title:Bioequivalence Study of 2 Sizes of SHR4640 Tablets Orally in Healthy Subjects
Status:Completed
updateDate:2024-01-23
Ctid:NCT06168929
Link: https://clinicaltrials.gov/ct2/show/NCT06168929
Conditions:HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT05513976
Conditions:Primary Gout and HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT04305392
Conditions:Hepatic ImpairmentLink: https://clinicaltrials.gov/ct2/show/NCT04620408
Conditions:Healthy SubjectsLink: https://clinicaltrials.gov/ct2/show/NCT04586803
Conditions:Primary Gout|HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT03131583
Conditions:GoutLink: https://clinicaltrials.gov/ct2/show/NCT03185793
Conditions:HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT03015948
Conditions:GoutLink: https://clinicaltrials.gov/ct2/show/NCT03211403
Conditions:Gout|HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT02890966
Conditions:Gout; HyperuricemiaLink: https://clinicaltrials.gov/ct2/show/NCT02815839
Conditions:Gout; HyperuricemiaProducts are for research use only; We do not sell to patients
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