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.
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- 화학식: C22H20FN5O3
- 분자량:421.42
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보관:
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
- 순도&문서
- References
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Help & FAQs
Biological Activity
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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.
|
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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분자량 421.42
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화학식 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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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
순도&문서
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
VU6081679 Related Classifications
HY-187535 Related Classifications
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