TAS-303
TAS-303 is an orally effective selective norepinephrine transporter (NET) inhibitor. TAS-303 inhibits human NET ligand binding with a Ki of 50.9 nM, and suppresses NET-mediated norepinephrine uptake with an IC50 of 38.9 nM. TAS-303 enhances norepinephrine-induced contraction in isolated rat urethral tissues, elevates plasma norepinephrine levels in rats, and increases urethral baseline pressure and leak point pressure. TAS-303 is applicable for research related to stress urinary incontinence, norepinephrine reuptake, and lower urinary tract function.
For research use only. We do not sell to patients.
- CAS No.: 1449371-87-2
- Formula: C22H20D7NO3
- Molecular Weight:360.50
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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
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
Human NET 50.9 nM (Ki) |
Human NET 38.9 nM (IC50) |
In Vitro
TAS-303 (3-3000 nM; 3 h) inhibits ligand binding to human NET, SERT, and DAT, with Ki values of 50.9, 1560, and 1290 nM, respectively, and exhibits selectivity for NET[1].
TAS-303 (3-3000 nM; preincubated at 25°C for 20 min) potently and selectively inhibits the uptake of [3H]norepinephrine in MDCK cells expressing human NET, with an IC50 of 38.9 nM[1].
TAS-303 (10-1000 nM; rat isolated urethral tissue) shifts the concentration-response curve of noradrenaline-induced urethral contraction to the left[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
In Vivo
TAS-303 (0.3-3 mg/kg; p.o.; single administration) dose-dependently increases the baseline urethral pressure in healthy female Sprague-Dawley rats, with a 38% increase in pressure observed at the dose of 3 mg/kg[1].
TAS-303 (0.3-3 mg/kg; p.o.; single administration) dose-dependently increases the leak point pressure in a rat model of vaginal distension-induced stress urinary incontinence, with a 26% increase observed at the dose of 3 mg/kg [1].
TAS-303 (10-100 mg/kg; p.o.; single administration) has no effect on the immobility time in the forced swimming test of healthy female Sprague-Dawley rats[1].
TAS-303 (1-10 mg/kg; p.o.; single administration) exerts no effects on cardiovascular parameters in conscious healthy dogs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague-Dawley (female, 10 weeks of age)[1]
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Dosage:3 mg/kg
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Administration:p.o.; once daily for 7 days
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Result:Increased plasma norepinephrine levels significantly compared to vehicle-treated rats.
Produced no differences in plasma epinephrine, dopamine, or serotonin levels compared to vehicle-treated rats.
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Animal Model:Sprague-Dawley (female, 11 weeks of age)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.; single dose
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Result:Produced a dose-dependent increase in urethral baseline pressure.
Increased urethral pressure significantly at doses of 1 mg/kg and 3 mg/kg compared to vehicle.
Increased urethral baseline pressure by 38% at the 3 mg/kg dose.
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Animal Model:Sprague-Dawley (female, 11 weeks of age, stress urinary incontinence induced by vaginal distention)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.; single dose
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Result:Produced a dose-dependent increase in leak point pressure (LPP).
Increased LPP significantly at doses of 1 mg/kg and 3 mg/kg compared to vehicle.
Increased LPP by 26% at the 3 mg/kg dose.
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Animal Model:Sprague-Dawley (female, 11 weeks of age)[1]
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Dosage:10 mg/kg; 30 mg/kg; 100 mg/kg
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Administration:p.o.; single dose
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Result:Produced no significant change in immobility time compared to vehicle-treated rats at all tested doses.
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Animal Model:Conscious dogs[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Produced no significant changes in systolic blood pressure, diastolic blood pressure, mean blood pressure, or heart rate compared to vehicle-treated dogs at all tested doses.
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Application
1. This compound can be used as a tracer
2. This compound can be used as an internal standard for quantitative analysis by NMR, GC-MS, or LC-MS.
Chemical Information
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CAS No. 1449371-87-2
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Unlabeled CAS 108640-65-9
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Molecular Weight 360.50
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Formula C22H20D7NO3
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SMILES
C(C(OC1CCNCC1)=O)(OC(C(C([2H])([2H])[2H])([2H])[2H])([2H])[2H])(C2=CC=CC=C2)C3=CC=CC=C3
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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.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
TAS-303 Related Classifications
HY-167227S Related Classifications
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