TRPV4 antagonist-7
TRPV4 antagonist-7 is a potent and selective TRPV4 antagonist with an IC50 of 0.2 nM against human targets. TRPV4 antagonist-7 binds to the voltage-sensor-like domain cavity of TRPV4 and inhibits channel activity through the formation of salt bridges, hydrogen bonds, and edge-to-face π-stacking interactions. TRPV4 antagonist-7 induces phospholipid accumulation in HepG2 C3A cells in vitro with an IC50 of 3.8 μM, and exhibits moderate inhibitory effects on CYP2D6 with an IC50 of 5.1 μM. TRPV4 antagonist-7 dose-dependently inhibits GSK1016790A (HY-19608)-induced bronchoconstriction in rats and cough in guinea pigs. TRPV4 antagonist-7 can be used in studies related to respiratory system diseases.
For research use only. We do not sell to patients.
- CAS No.: 3050594-88-9
- Formula: C26H30ClFN4O3
- Molecular Weight:500.99
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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]|
hTRPV4 0.2 nM (IC50) |
CYP2D6 5.1 μM (IC50) |
In Vitro
TRPV4 antagonist-7 (compound 39) (10 min) potently inhibits hTRPV4-mediated calcium mobilization in primary human airway smooth muscle cells, with an IC50 of 0.2 nM[1].
TRPV4 antagonist-7 (4 μM; 120 min) exhibits favorable metabolic stability in cryopreserved hepatocytes across species, with the highest intact fraction observed in canine hepatocytes (97.0%) and the lowest in miniature pig hepatocytes (77.1%)[1].
TRPV4 antagonist-7 exhibits moderate inhibitory activity against human CYP2D6 (IC50 = 5.1 μM), with a low risk of inhibiting other major human CYP subtypes[1].
TRPV4 antagonist-7 inhibits hERG channels with an IC50 of 2743 nM, indicating a controllable safety margin relative to its potency against hTRPV4[1].
TRPV4 antagonist-7 exhibits high intrinsic permeability in Caco-2 cells, with an efflux ratio of 31, which is significant yet controllable[1].
TRPV4 antagonist-7 exhibits favorable solubility (274 μM), moderate human liver microsomal stability (HLM Clint = 21 μL/min/mg), and a human plasma free fraction of 5%[1].
TRPV4 antagonist-7 (0.0099-10 μM; 24 h) induces phospholipidosis in human HepG2 clone C3A cells, with an IC50 of 3.8 μM[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
TRPV4 antagonist-7 (0.03-10 mg/kg; p.o.; single administration) dose-dependently inhibits GSK1016790A-induced cough in Dunkin-Hartley guinea pigs[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Brown Norway (male, 225-250 g)[1]
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Dosage:0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Dose-dependently inhibited GSK1016790A-induced bronchoconstriction.
Significantly reduced PenH values compared to vehicle-treated challenged rats at doses of 0.3 mg/kg and above.
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Animal Model:Dunkin-Hartley (male, 300-500 g)[1]
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Dosage:0.03 mg/kg; 0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; single dose
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Result:Dose-dependently inhibited GSK1016790A-induced cough.
Significantly reduced the number of coughs compared to vehicle-treated challenged guinea pigs at doses of 0.3 mg/kg, 1 mg/kg, 3 mg/kg, and 10 mg/kg.
Chemical Information
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CAS No. 3050594-88-9
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Molecular Weight 500.99
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Formula C26H30ClFN4O3
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SMILES
O=C(NC1=CC(Cl)=C(C=C1)CN2CCC[C@]([C@@](C)(CO)O)(C2)[H])C3=CN(N=C3C)C4=CC=C(C=C4)F
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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)
TRPV4 antagonist-7 Related Classifications
HY-187364 Related Classifications
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