VU6008055
Based on 1 Customer Validation
VU6008055 (AF98943) is a brain-penetrant, orally active and selective muscarinic acetylcholine receptor subtype 4 (mAChR4) activator with human EC50 values of 73.4 nM. VU6008055 potentiates mAChR4 receptor activity in the presence of acetylcholine, and exhibits no activity at mAChR1, mAChR3, or mAChR5. VU6008055 can be used for the research of schizophrenia, parkinson’s disease, alzheimer’s disease.
Nur für Forschungszwecke. Wir verkaufen nicht an Patienten.
- Reinheit: 99.43%
- CAS. Nr.: 2170551-59-2
- Formel: C20H21N5OS
- Molecular Weight:379.48
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Speicherung:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
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Biologische Aktivität
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Chemical Information
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Lösungsmittel & Löslichkeit
- Reinheit & Dokumentation
- Verweise
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Help & FAQs
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GPCR/G Protein Compound Library
HY-L006
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Neuronal Signaling Compound Library
HY-L013
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CNS-Penetrant Compound Library
HY-L028
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Orally Active Compound Library
HY-L061
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Neurotransmitter Receptor Compound Library
HY-L062
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Anti-Alzheimer's Disease Compound Library
HY-L069
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Anti-Parkinson's Disease Compound Library
HY-L085
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Neurodegenerative Disease-related Compound Library
HY-L086
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Membrane Protein-targeted Compound Library
HY-L149
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Membrane Receptor-targeted Compound Library
HY-L150
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Highly Selective Activators Library
HY-L159
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Bioactive Compound Library Max
HY-L181
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MCE Bioactive Compound Library
HY-L001V
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Bioactive Compound Library
HY-L001
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High-Throughput Bioactive Compound Library
HY-L205
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Lactylation Compound Library
HY-L249
Biologische Aktivität
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mAChR4 73.4 nM (EC50) |
VU6008055 potently potentiates acetylcholine-evoked calcium mobilization in CHO cells expressing human M4 with an EC50 of 73.4 nM and a maximum response of 91% of the acetylcholine maximum[1].
VU6008055 potently potentiates acetylcholine-evoked calcium mobilization in CHO cells expressing rat M4 with an EC50 of 19.5 nM and a maximum response of 81% of the acetylcholine maximum[1].
VU6008055 does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 at concentrations up to 15 μM and does not cause time-dependent CYP inhibition[1].
VU6008055 does not form reactive intermediates/metabolites in human liver microsomes[1].
VU6008055 (10 μM) has no significant inhibitory activity against cardiac ion channels[1].
VU6008055 (4 h) shows moderate metabolic turnover in human hepatocytes, with low to high turnover across other preclinical species, and forms two predominant metabolites (MT4, MT5) in humans[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 | Tmax | Cmax | AUC0-∞ | F |
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| Rat[1] | 1 mg/kg | i.v. | 2.63 h | 2.65 h | 4.7 mL/min/kg | 0.7 L/kg | / | / | / | / |
| Rat[1] | 3 mg/kg | p.o. | / | / | / | / | 1.5 h | 1695 ng/mL | 14801 ng·h/mL | >100 % |
| Rat[1] | 30 mg/kg | p.o. | / | / | / | / | 3.0 h | 8985 ng/mL | 101444 ng·h/mL | 89 % |
| Dog[1] | 1 mg/kg | i.v. | 4.17 h | 5.05 h | 5.0 mL/min/kg | 1.4 L/kg | / | / | / | / |
| Dog[1] | 3 mg/kg | p.o. | / | / | / | / | 2.0 h | 766 ng/mL | 5920 ng·h/mL | 54 % |
| Monkey[1] | 1 mg/kg | i.v. | 4.54 h | 3.16 h | 5.0 mL/min/kg | 0.9 L/kg | / | / | / | / |
| Monkey[1] | 3 mg/kg | p.o. | / | / | / | / | 2.0 h | 960 ng/mL | 4696 ng·h/mL | 44 % |
| Pig[1] | 2 mg/kg | i.v. | 5.50 h | 4.9 h | 7.7 mL/min/kg | 2.2 L/kg | / | / | / | / |
| Pig[1] | 5 mg/kg | p.o. | / | / | / | / | 1.2 h | 600 ng/mL | 8000 ng·h/mL | 50 % |
VU6008055 (0.3-3 mg/kg; p.o.) attenuates MK-801 (HY-15084B)-induced hyperlocomotion in male Sprague-Dawley rats[1].
VU6008055 (3 mg/kg; p.o.; twice daily; 7 days) does not induce tolerance to its antipsychotic-like activity in male Sprague-Dawley rats, producing ~50.6% reversal of Amphetamine-induced hyperlocomotion[1].
VU6008055 (0.3-30 mg/kg; p.o.) only moderately disrupts conditioned avoidance responses in male Wistar-Han rats at a high dose of 30 mg/kg, with no significant effect at lower doses[1].
VU6008055 (1-10 mg/kg; p.o.) dose-dependently blocks Amphetamine-induced brain activation in male Sprague-Dawley rats[1].
VU6008055 (0.1-10 mg/kg; p.o.) dose-dependently increases high gamma power, an EEG marker of arousal, in awake male Sprague-Dawley rats[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)[1]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 0.56 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.
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Result:Produced a robust dose-dependent blockade of Amphetamine-induced hyperlocomotion, with mean reversal percentages of 8.1% (0.1 mg/kg), 33% (0.3 mg/kg), 26% (0.56 mg/kg), 51% (1 mg/kg), 44% (3 mg/kg), and 63% (10 mg/kg).
Reached mean unbound brain concentrations ranging from 0.71 nM (0.1 mg/kg) to 68.6 nM (10 mg/kg).
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Animal Model:Sprague-Dawley (male)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg
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Administration:p.o.
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Result:Attenuated MK-801-induced hyperlocomotion, with mean reversal percentages of 7.4% (0.3 mg/kg), 24.3% (1 mg/kg), and 49.1% (3 mg/kg).
Produced a statistically significant effect at the 3 mg/kg dose.
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Animal Model:Sprague-Dawley (male)[1]
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Dosage:3 mg/kg
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Administration:p.o.; twice daily; 7 days
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Result:Produced a 50.6% attenuation of Amphetamine-induced hyperlocomotion after chronic dosing.
Showed similar magnitude of attenuation to the 45.7% reduction observed after a single acute dose of 3 mg/kg.
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Animal Model:Wistar-Han (male)[1]
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Dosage:0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg; 30 mg/kg
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Administration:p.o.
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Result:Had only a moderate effect on avoidance and escape responses at 30 mg/kg.
Did not significantly disrupt avoidance responses compared to vehicle controls at lower doses (0.3-10 mg/kg).
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Animal Model:Sprague-Dawley (male)[1]
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Dosage:1 mg/kg; 10 mg/kg
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Administration:p.o.
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Result:Dose-dependently attenuated amphetamine-evoked increases in cerebral blood volume (CBV) in the caudate putamen, nucleus accumbens, prefrontal cortex, cingulate cortex, medial dorsal thalamic nucleus, and ventral posterior lateral/ventral posterior medial thalamic nuclei.
Produced no significant CBV responses when administered alone.
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Animal Model:Sprague-Dawley (male)[1]
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Dosage:0.1 mg/kg; 0.3 mg/kg; 1 mg/kg; 3 mg/kg; 10 mg/kg
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Administration:p.o.
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Result:Produced a robust, dose-dependent increase in high gamma power (30-100 Hz) during wake periods.
Induced significant increases at 0.3 mg/kg (78-79, 80-100 Hz), 1 mg/kg (78-100 Hz), 3 mg/kg (89-100 Hz), and 10 mg/kg (80-100 Hz).
Chemical Information
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CAS. Nr. 2170551-59-2
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Appearance Solid
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Molecular Weight 379.48
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Formel C20H21N5OS
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Color Off-white to light yellow
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SMILES
CC1=NN=C(SC2=C3N=CN=C2NCC4=CC=C(C(C)(O)C)C=C4)C3=C1C
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Synonyms
AF98943
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Versand
Room temperature in continental US; may vary elsewhere.
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Speicherung
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Lösungsmittel & Löslichkeit
DMSO : 100 mg/mL (263.52 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Konzentration (Stammlösung) × Volumen (Stammlösung) = Konzentration (Ziellösung) × Volumen (Ziellösung)
Reinheit & Dokumentation
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Data Sheet (279 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Handling Instructions (2659 KB)
Verweise
[1]. Engers JL, et al. Discovery of Pre-Clinical Candidate VU6008055/AF98943: A Highly Selective, Orally Bioavailable, and Structurally Distinct Tricyclic M4 Muscarinic Acetylcholine Receptor Positive Allosteric Modulator (PAM) with Robust In Vivo Efficacy. ACS Chem Neurosci. 2025;16(11):2141-2162. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.6352 mL | 13.1759 mL | 26.3518 mL | 65.8796 mL |
| 5 mM | 0.5270 mL | 2.6352 mL | 5.2704 mL | 13.1759 mL | |
| 10 mM | 0.2635 mL | 1.3176 mL | 2.6352 mL | 6.5880 mL | |
| 15 mM | 0.1757 mL | 0.8784 mL | 1.7568 mL | 4.3920 mL | |
| 20 mM | 0.1318 mL | 0.6588 mL | 1.3176 mL | 3.2940 mL | |
| 25 mM | 0.1054 mL | 0.5270 mL | 1.0541 mL | 2.6352 mL | |
| 30 mM | 0.0878 mL | 0.4392 mL | 0.8784 mL | 2.1960 mL | |
| 40 mM | 0.0659 mL | 0.3294 mL | 0.6588 mL | 1.6470 mL | |
| 50 mM | 0.0527 mL | 0.2635 mL | 0.5270 mL | 1.3176 mL | |
| 60 mM | 0.0439 mL | 0.2196 mL | 0.4392 mL | 1.0980 mL | |
| 80 mM | 0.0329 mL | 0.1647 mL | 0.3294 mL | 0.8235 mL | |
| 100 mM | 0.0264 mL | 0.1318 mL | 0.2635 mL | 0.6588 mL |
VU6008055 Related Classifications
Art. -Nr.: HY-176200
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- VU6008055
- 2170551-59-2
- AF98943
- VU 6008055
- VU-6008055
- AF 98943
- AF-98943
- mAChR
- M3 muscarinic receptors
- M1 muscarinic receptors
- parkinson’s disease
- alzheimer’s disease
- M2 muscarinic receptors
- Sprague-Dawley rats
- M5 muscarinic receptors
- muscarinic acetylcholine receptor subtype 4
- schizophrenia
- CHO cells
- Inhibitor
- inhibitor
- inhibit