VCU-1012
VCU-1012 is a serotonin 2A receptor (5-HT2AR) agonist, with a pEC50 of 5.81 and a pKi of 5.75 against human receptors. VCU-1012 binds to the canonical orthosteric binding pocket of 5-HT2AR, triggers intracellular calcium release and Gαq protein dissociation, and its agonistic activity depends on specific amino acid residues in the receptor binding pocket. VCU-1012 can be used in research related to depression, anxiety disorders, and chemotherapy-induced mood disorders.
For research use only. We do not sell to patients.
- Formula: C12H15ClN4
- Molecular Weight:250.73
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
All 5-HT Receptor Isoforms
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Biological Activity
Description
IC50 & Target
[1]|
5-HT2A Receptor 5.75 (pKi) |
5-HT2A Receptor 5.81 (pEC50) |
In Vitro
VCU-1012 (compound 15) displaces [3H]ketanserin in HEK293 cells stably expressing human 5-HT2AR, with a pKi of 5.75 for 5-HT2AR[1].
VCU-1012 induces Ca2+ mobilization in HEK293 cells stably expressing 5-HT2AR, with a pEC50 of 5.81 and an Emax of 46.25%, exhibiting partial agonist activity; Volinanserin (HY-14940) completely blocks VCU-1012-induced Ca2+ mobilization[1].
VCU-1012 induces concentration-dependent dissociation of Gαq in HEK293 cells expressing 5-HT2AR, exhibiting partial agonist activity relative to 5-HT; this effect is reversed by the 5-HT2AR antagonist volinanserin and is absent in parental HEK293 cells[1].
VCU-1012 (10 μM) does not induce significant 5-HT3R-mediated inward currents in Flp-In T-REx HEK293 cells expressing 5-HT3R, indicating that VCU-1012 has no detectable 5-HT3R agonist activity[1].
VCU-1012 exhibits low binding affinity for 5-HT1BR, 5-HT2CR and 5-HT7R, with Ki values all > 1000 nM; it shows overall low off-target activity in screening against more than 40 receptors and transporters[1].
VCU-1012 (100 μM) displaces < 50% of [3H]LSD; it can completely displace [3H]LSD binding at lower [3H]LSD concentrations, but its apparent affinity is lower than that observed in the [3H]ketanserin displacement assay[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
In Vivo
VCU-1012 (1 mg/kg; i.p.; 24 h after a single administration) reduces immobility time in the forced swim test of WT mice, but exerts no such effect in 5-HT2AR KO mice; it does not significantly alter spontaneous horizontal activity or the time spent in the central area of the open field in WT mice during the same period[1].
VCU-1012 (1 mg/kg; i.p.; administered on day 15 after the final dose of paclitaxel, with tests conducted 24 h later) abolishes the light-avoiding phenotype observed in Paclitaxel (HY-B0015)-treated mice in the light-dark box test; administration of VCU-1012 alone does not alter anxiety-like behaviors, and no significant changes are observed in the number of light-dark box crossings among all groups[1].
VCU-1012 (1 mg/kg; i.p.; 24 h after a single administration) increases the total dendritic spine density and mature mushroom-shaped dendritic spine density in the prefrontal cortex of WT mice, with an effect comparable to that of psilocybin; VCU-1012 does not significantly alter stubby or thin spines, and the increases in total dendritic spines and mushroom-shaped dendritic spines are abolished in 5-HT2AR KO mice[1].
VCU-1012 (1 mg/kg; i.p.; single administration) does not significantly alter charcoal meal propulsion in the small intestine of mice, whereas Quipazine (HY-W028142) (5 mg/kg; i.p.) significantly inhibits small intestinal propulsion[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:wild-type; 5-HT2A receptor knockout[1]
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Dosage:1 mg/kg
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Administration:i.p.; single dose
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Result:Showed charcoal transit similar to vehicle-treated animals.
Did not produce significant reduction in gastrointestinal motility.
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Animal Model:wild-type[1]
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Dosage:0.1 mg/kg; 0.5 mg/kg; 1.0 mg/kg
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Administration:i.p.; single dose
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Result:Produced a dose-dependent robust increase in head-twitch response (HTR) counts that peaked during the first 15 minutes post-administration and lasted for more than 45 minutes.
Showed significantly higher cumulative HTR counts over the first 30 minutes at 0.5 mg/kg and 1.0 mg/kg compared to vehicle.
Had HTR induced by 1.0 mg/kg fully blocked by pretreatment with Volinanserin.
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Animal Model:wild-type; 5-HT2A receptor knockout[1]
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Dosage:1 mg/kg
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Administration:i.p.; single dose
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Result:Reduced immobility time in the forced-swim test compared to vehicle in wild-type mice.
Did not affect immobility time in 5-HT2A receptor knockout mice.
Showed locomotor activity and time spent in the center of an open field arena 24 hours post-treatment similar to vehicle-treated wild-type mice.
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Animal Model:wild-type[1]
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Dosage:1 mg/kg
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Administration:i.p.; single dose
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Result:Reversed the reduced time spent in the light compartment (indicative of anxiety-like behavior) induced by Paclitaxel, 24 hours post-administration.
Did not affect anxiety-like behavior when administered alone.
Showed no alteration in the number of compartment crosses, indicating no change in locomotor activity.
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Animal Model:wild-type; 5-HT2A receptor knockout[1]
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Dosage:1 mg/kg
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Administration:i.p.; single dose
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Result:Increased overall dendritic spine density in the frontal cortex of wild-type mice, comparable to the effect induced by psilocybin.
Drove the increase via a rise in mature mushroom spine density, with no changes in stubby or immature thin spine density in wild-type mice.
Did not increase overall dendritic spine density or mushroom spine density in 5-HT2A receptor knockout mice.
Chemical Information
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Molecular Weight 250.73
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Formula C12H15ClN4
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SMILES
C1(N2CCNCC2)=NC=C3C=CC=CC3=N1.Cl
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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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Calcium Spark Assay
Calcium sparks are localized, transient increases in intracellular calcium concentration ([Ca2+]i) that occur in cardiac myocytes and represent elementary events underlying excitation-contraction coupling. These events are generated by the coordinated opening of clusters of ryanodine receptors (RyRs) on the sarcoplasmic reticulum membrane, leading to a brief release of Ca2+ into the cytosol. The detection and analysis of calcium sparks provide insights into the mechanisms of calcium handling and signaling in cardiac cells. Imaging techniques using fluorescent calcium indicators such as Fluo-3 are employed to visualize these subcellular calcium transients with high spatial and temporal resolution. The protocol is based on established methodologies described in primary literature for both experimental measurement and automated analysis of calcium sparks.
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Ca2+ Staining Technique
Ca2+ staining is an experimental technique that utilizes specific fluorescent probes (such as Fluo-4 AM, Fura-2, etc.) to qualitatively or quantitatively detect dynamic changes in intracellular Ca2+ concentrations; this is achieved by monitoring the changes in fluorescent signals generated when these probes bind to free intracellular calcium ions. The underlying principle relies primarily on the presence of chelating groups within the probe's molecular structure that possess high affinity for calcium ions.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)