URAT1-IN-16
URAT1-IN-16 is an orally active URAT1 inhibitor with an IC50 value of 0.19 μM. URAT1-IN-16 also functions as an NLRP3 inflammasome pathway inhibitor by effectively suppressing mature IL-1β secretion (IC50 = 2.52 μM). URAT1-IN-16 exhibits remarkable serum uric acid-lowering and anti-inflammatory activities in vivo, and can be used for hyperuricemia and gout research.
For research use only. We do not sell to patients.
- CAS No.: 2864442-74-8
- Formula: C28H23BrN4O3S2
- Molecular Weight:607.54
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Protocols
- Purity & Documentation
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Biological Activity
Description
IC50 & Target
[1]|
URAT1 0.19 μM (IC50) |
IL-1β 2.52 μM (IC50) |
In Vitro
URAT1-IN-16 (Compound 2) (30 min pre-incubation; 5 min uptake assay) potently inhibits human URAT1-mediated 14C-uric acid uptake in hURAT1-transfected HEK293T cells (IC50 = 0.19 μM)[1].
URAT1-IN-16 (up to 10 μM; 15 min) dose-dependently inhibits mature IL-1β secretion and active Caspase-1 generation in LPS-primed and ATP-stimulated mouse bone marrow-derived macrophages (BMDMs) (IC50 = 2.52 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:BMDMs from 6-week-old male C57BL/6 WT mice were treated with LPS (1 μg/mL) and ATP (5 mM)
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Concentration:Varying gradient concentrations up to 10 μM
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Incubation Time:15 min
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Result:Dose-dependently inhibited mature IL-1β secretion with an IC50 value of 3.39 μM.
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Cell Line:THP-1 cells
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Concentration:10 and 20 μM
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Incubation Time:30 min
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Result:Reduced the generation of active cleaved caspase-1 in a distinct dose-dependent manner without altered levels of pro-Caspase-1, NEK7, or ASC.
Parmacokinetics
In Vivo
URAT1-IN-16 (2 mg/kg; p.o.; single dose) significantly decreases serum uric acid (SUA) levels in a rat model of hyperuricemia[1].
URAT1-IN-16 (500-1500 mg/kg; p.o.; single dose) exhibits high acute safety profiles with a maximum tolerated dose (MTD) above 1000 mg/kg in healthy Kunming mice[1].
URAT1-IN-16 (50 mg/kg; p.o.; every other day; for 28 days) shows favorable subacute tolerance with no organic toxicity or weight differences in healthy Kunming mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Mouse model of acute hyperuricemia (induced by hypoxanthine and potassium oxonate)[1]
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Dosage:0.125, 0.25, 0.5, 1, 2 mg/kg
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Administration:Oral gavage (p.o.), single dose
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Result:Reduced serum uric acid levels from 1162.0 μM to a normal physiological range of 143.20 μM within 4 h at 2 mg/kg, achieving a 96.8% reduction rate.
Exhibited a clear dose-dependent urate-lowering effect, with reduction rates of 93.4% (1 mg/kg), 72.6% (0.5 mg/kg), and 53.1% (0.25 mg/kg), and established a minimum effective dose of 0.25 mg/kg.
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Animal Model:Rat model of hyperuricemia [1]
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Dosage:2 mg/kg
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Administration:Oral gavage (p.o.), single dose
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Result:Induced a marked reduction in serum uric acid levels from 917.80 μM to 173.80 μM within 4 h post dosing, corresponding to a 91.87% decrease.
Demonstrated cross-species urate-lowering activity and showed over 3-fold superior efficacy compared with lesinurad.
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Animal Model:healthy Kunming mice (10-12 g, male and female)[1]
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Dosage:500, 1000, 1500 mg/kg
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Administration:Oral gavage (p.o.), single dose
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Result:Established a maximum tolerated dose (MTD) above 1000 mg/kg with 100% survival within 1 week.
Showed 80% survival at 1500 mg/kg, with two female mouse deaths occurring within 72 h at the highest dose.
Did not induce observable abnormalities in behavior, posture, appearance, or body weight gain at the MTD.
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Animal Model:healthy Kunming mice (10-12 g, male and female)[1]
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Dosage:50 mg/kg
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Administration:Oral gavage (p.o.), every other day for 28 days
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Result:Produced no mortality and no observable adverse behavioral effects (lethargy, convulsion, anorexia, or piloerection) during 28 days of treatment.
Maintained normal body weight gain comparable to vehicle control and showed no significant changes in major organ coefficients.
Did not induce histopathological lesions in heart, liver, spleen, lung, or kidney tissues.
Chemical Information
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CAS No. 2864442-74-8
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Molecular Weight 607.54
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Formula C28H23BrN4O3S2
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SMILES
BrC(C=C1)=CC=C1S(NC(C(C)SC2=NC3=NC=CC=C3N2C4=CC=C(C5CC5)C6=C4C=CC=C6)=O)(=O)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
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Pyroptosis Solutions
Pyroptosis is a lytic inflammatory cell-death pathway executed by gasdermin pores, most classically through inflammasome-mediated activation of caspase-1, cleavage of gasdermin D, membrane pore formation, LDH release, and secretion of IL-1β and IL-18. The canonical pathway is commonly modeled by priming cells with an inflammatory signal such as LPS to induce pro-IL-1β and inflammasome components, followed by an activation signal such as ATP or nigericin to activate NLRP3, ASC speck formation, caspase-1 cleavage, GSDMD cleavage, cytokine release, and pyroptotic membrane rupture. The non-canonical pathway is triggered when cytosolic LPS activates mouse caspase-11 or human caspase-4/5, leading to GSDMD cleavage and pyroptosis, and this can secondarily activate NLRP3-dependent IL-1β release. Pyroptosis is linked to inflammatory injury, infection, cancer, liver disease, ocular disease, placental inflammation, and other disease phenotypes, but unresolved questions include which gasdermin fam
Purity & Documentation
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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