VU6081679
VU6081679 is an orally active positive allosteric modulator of mGlu8 with blood-brain barrier permeability. VU6081679 binds to the extracellular allosteric pocket at the TM6/TM7 junction of mGlu8, and anchors via hydrophobic interactions and water-mediated polar contacts, thereby stabilizing the active state of the receptor and exerting positive allosteric regulatory effects. VU6081679 can be used for research on Parkinson's disease.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Fòrmula: C22H20FN5O3
- Peso molecular:421.42
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Almacenamiento:
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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Actividad biológica
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mGlu8 |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| HEK293 | EC50 |
211 nM
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Positive allosteric modulation of rat metabotropic glutamate receptor 8 (mGlu8) in HEK293 cells stably coexpressing rat mGlu8 and promiscuous G protein Gα15, measured via calcium mobilization assay using Fluo-4-AM calcium indicator dye with a triple-add protocol.
Positive allosteric modulation of rat metabotropic glutamate receptor 8 (mGlu8) in HEK293 cells stably coexpressing rat mGlu8 and promiscuous G protein Gα15, measured via calcium mobilization assay using Fluo-4-AM calcium indicator dye with a triple-add protocol.
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42460925 |
| HEK293 | EC50 |
190 nM
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Positive allosteric modulation of mouse metabotropic glutamate receptor 8 (mGlu8) in HEK293 cells stably coexpressing mouse mGlu8 and promiscuous G protein Gα15, measured via calcium mobilization assay using Fluo-4-AM calcium indicator dye with a triple-add protocol.
Positive allosteric modulation of mouse metabotropic glutamate receptor 8 (mGlu8) in HEK293 cells stably coexpressing mouse mGlu8 and promiscuous G protein Gα15, measured via calcium mobilization assay using Fluo-4-AM calcium indicator dye with a triple-add protocol.
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42460925 |
| HEK293 | EC50 |
162 nM
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Positive allosteric modulation of human metabotropic glutamate receptor 8 (mGlu8) in HEK293 cells stably coexpressing human mGlu8 and promiscuous G protein Gα15, measured via calcium mobilization assay using Fluo-4-AM calcium indicator dye with a triple-add protocol.
Positive allosteric modulation of human metabotropic glutamate receptor 8 (mGlu8) in HEK293 cells stably coexpressing human mGlu8 and promiscuous G protein Gα15, measured via calcium mobilization assay using Fluo-4-AM calcium indicator dye with a triple-add protocol.
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42460925 |
VU6081679 (1 μM-0.1 mM; 4.5 min) exerts a significant intracellular calcium mobilization-promoting effect in HEK293 cells stably co-expressing rat, mouse or human mGlu8 and Gα15 proteins[1].
VU6081679 (1 μM-0.1 mM) exerts weak or no significant calcium mobilization-promoting effect in HEK293/CHO cells stably expressing rat mGlu1, mGlu5, and mGlu7[1].
VU6081679 (1 μM-0.1 mM) exerts no significant thallium flux-promoting effect in HEK293/CHO cells stably expressing rat mGlu2, mGlu3, and mGlu4[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | CLplasma | T1/2 (Elimination) | Vss | Bioavailability |
|---|---|---|---|---|---|---|
| Rat[1] | 10 mg/kg | p.o. | 22.4 mL/min/kg | 0.91 | 1.38 L/kg | 102 % |
VU6081679 (56.6 mg/kg; i.p.; single administration; testing performed 30 min later) significantly reverses haloperidol-induced catalepsy in wild-type mouse models[1].
VU6081679 (56.6 mg/kg; i.p.; single administration; tested 30 min later) fails to reverse the catalepsy response in the haloperidol-induced catalepsy model of mGlu8 knockout mice[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 (male, 320-360 g, haloperidol-induced catalepsy model)[1]
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Dosage:1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.; single dose; 90 min
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Result:Produced 20.7% reversal of catalepsy at 1 mg/kg.
Produced 31.1% reversal of catalepsy at 3 mg/kg.
Produced 75.7% reversal of catalepsy at 10 mg/kg.
Achieved plasma total exposure of 21.1 μM, plasma free exposure of 0.68 nM, brain total exposure of 8.77 μM, and brain free exposure of 332 nM at 10 mg/kg.
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Animal Model:C57Bl6/J (male and female, 12-15 weeks of age, haloperidol-induced catalepsy model); global mGlu8 knockout (male and female, 12-15 weeks of age, haloperidol-induced catalepsy model)[1]
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Dosage:56.6 mg/kg
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Administration:i.p.; single dose; 30 min
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Result:Reduced catalepsy latency from ~180 s to ~50 s in wild-type male mice, with statistically significant reversal.
Reduced catalepsy latency from ~180 s to ~85 s in wild-type female mice, with statistically significant reversal.
Produced no reduction in catalepsy latency in mGlu8 knockout male or female mice.
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Animal Model:wild-type (male, female); mGlu8 knockout (male, female)[2]
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Dosage:56.6 mg/kg
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Administration:i.p.; single dose; 30 mim
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Result:Reduced latency to withdraw to 50.4 seconds at 30 minutes, 63.7 seconds at 60 minutes, and 106.0 seconds at 120 minutes in male wild-type mice.
Reduced latency to withdraw to 85.4 seconds at 30 minutes, 104.0 seconds at 60 minutes, and 136.8 seconds at 120 minutes in female wild-type mice.
Showed no significant reduction in latency to withdraw in male or female mGlu8 knockout mice at any time point.
Chemical Information
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Peso molecular 421.42
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Fòrmula C22H20FN5O3
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SMILES
O=C1N(CC2=CC(F)=C(C3=CN(C)N=C3)N=C2)N=C(C4=CC(OC)=C(OC)C=C4)C=C1
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VU6081679 Related Classifications
HY-187535 Related Classifications
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