VU6025733
VU6025733 (AG06827) is a highly selective, orally active and blood-brain barrier-penetrant positive allosteric modulator of the muscarinic acetylcholine receptor subtype M4 (M4 mAChR). VU6025733 exerts a potentiating effect on acetylcholine-induced receptor activation with an EC50 of 23 nM for hM4 and 55 nM for rM4. VU6025733 shows high selectivity over other muscarinic acetylcholine receptor subtypes, dose-dependently reduces amphetamine-induced hyperlocomotion in rats. VU6025733 is applicable to the research of schizophrenia, Parkinson's disease, and Alzheimer's disease.
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- Fòrmula: C20H18D5N5O3
- Peso molecular:386.46
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
- Pureza y Documentación
- Referencias
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Help & FAQs
Actividad biológica
VU6025733 (10-point serial dilutions (1:3)) potently potentiates human M4/Gqi5-CHO cells (EC50 = 33 nM) and rat M4/Gqi5-CHO cells (EC50 = 62 nM), while showing no activity in human or rat M1, M2, M3, or M5 muscarinic receptor-expressing CHO cells[1].
VU6025733 inhibits hERG channels with an IC50 of 4.6 μM[1].
VU6025733 induces cytotoxic effects in HepaRG 3D spheroids, including reduced glutathione content and cellular ATP, with MEC values of 9.7 μM and 4.2 μM, respectively[1].
VU6025733 decreases oxygen consumption rate (MEC = 2.0 μM) and increases extracellular acidification rate (MEC = 7.1 μM) in HepG2 cells, indicating electron transport chain inhibition[1].
VU6025733 has high brain penetration potential with no P-glycoprotein efflux, as shown by an efflux ratio of 0.80 and Papp (A-B) of 12.7 × 10-6 cm/s in MDCKII-MDR1 cells[1].
VU6025733 shows minimal inhibition of CYP1A2, CYP2C9, and CYP3A4 (IC50 ≥ 19.3 μM) and moderate inhibition of CYP2D6 (IC50 = 8.4 μM)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
| Species | Dose | Route | T1/2 | MRT | CLplasma | Vss | Plasma Concentration | CLunbound | Brain Concentration | Brain distribution | Tmax | Cmax | AUC0-∞ | Bioavailability |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 1 mg/kg | i.v. | 5.67 h | 3.83 h | 5.26 mL/min/kg | 1.21 L/kg | / | / | / | / | / | / | / | / |
| Rat[1] | 3 mg/kg | p.o. | / | / | / | / | / | / | / | / | 0.75 h | 1783 ng/mL | 6753 ng·h/mL | 74.1 % |
| Rat[1] | 10 mg/kg | p.o. | / | / | / | / | 3974 ng/mL | 39.7 ng/mL | 1086 ng/g | 17.4 ng/g | / | / | / | / |
| Rat[1] | 15 mg/kg | p.o. | / | / | / | / | 6463 ng/mL | 64.6 ng/mL | 1587 ng/g | 25.4 ng/g | / | / | / | / |
| Rat[1] | 30 mg/kg | p.o. | / | / | / | / | 11477 ng/mL | 115 ng/mL | 3157 ng/g | 50.5 ng/g | / | / | / | / |
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)[1]
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Dosage:10 mg/kg; 15 mg/kg; 30 mg/kg
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Administration:p.o.; single administration
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Result:Produced a 25.6% reversal of induced hyperlocomotion, with a mean unbound brain concentration of 17.4 ng/g.
Produced a 34.0% reversal of induced hyperlocomotion, with a mean unbound brain concentration of 25.4 ng/g.
Produced a 39.7% reversal of induced hyperlocomotion, with a mean unbound brain concentration of 50.5 ng/g.
Significantly reduced total ambulation.
Chemical Information
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Unlabeled Cas 3084929-79-0
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Peso molecular 386.46
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Fòrmula C20H18D5N5O3
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SMILES
CC1=C(C)C(N2CCC(OC3=CC=C4OC([2H])([2H])C([2H])([2H])OC4=C3)([2H])CC2)=NN5C1=NN=C5
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Synonyms
AG06827
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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)
VU6025733 Related Classifications
HY-181559S Related Classifications
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- VU6025733
- AG06827
- VU 6025733
- VU-6025733
- AG 06827
- AG-06827
- mAChR
- M4 muscarinic acetylcholine receptor positive allosteric modulator
- orally active
- blood-brain barrier penetrant
- potentiate acetylcholine-mediated M4 mAChR activation
- hM4/Gqi5-CHO cells
- MDCKII-MDR1 transfected cells
- HepaRG 3D spheroids
- HepG2 cells
- rat amphetamine-induced hyperlocomotion model
- SD rat
- schizophrenia
- Parkinson's disease
- Alzheimer's disease
- Inhibitor
- inhibitor
- inhibit