AVN-492 |
| رقم الكتالوجGC30907 |
AVN-492 هو مضاد محدد للغاية وعالي الانتقائية مع تقارب بيكومولار مع 5-HT6R (Ki = 91 pM)
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1220646-23-0
Sample solution is provided at 25 µL, 10mM.
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AVN-492 is a very specific and highly-selective antagonist with picomolar affinity to 5-HT6R (Ki=91 pM).
The affinity of AVN-492 to bind to 5-HT6R (Ki=91 pM) is more than three orders of magnitude higher than that to bind to the only other target, 5-HT2BR, (Ki=170 nM). Thus, AVN-492 displays great 5-HT6R selectivity against all other serotonin receptor subtypes, and is extremely specific against any other receptors such as adrenergic, GABAergic, dopaminergic, histaminergic, etc[1].
In rats, the plasma, brain, and CSF concentrations of the PO administered AVN-492 are dose-dependent. The drug concentration curves for the plasma and brain are of hyperbolic shape and at all doses the brain-plasma ratio is near 11%. The drug concentration in CSF, however, is nearly linearly dependent on the dose, reaching 50% of the plasma level at 10mg/kg. In mice, the plasma and brain concentrations of AVN-492, given IV at a dose of 2 mg/kg, decreased with time but at both time points, 15 min and 60 min, the brain/plasma ratio (mean±SEM) is nearly the same, at 13.2±0.7% and 9.0±1.5%, respectively. This indicates that the steady-state concentration gradient of AVN-492 is established by at least 15 min after the drug administration[1].
[1]. Ivachtchenko AV, et al. AVN-492, A Novel Highly Selective 5-HT6R Antagonist: Preclinical Evaluation. J Alzheimers Dis. 2017;58(4):1043-1063.
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Kinase experiment: |
AVN-492 is dissolved into 100% DMSO to a concentration of 10mM. This DMSO solution is then diluted 50-fold with either anMQ water or a buffer with corresponding pH[1].The Caco-2 permeability assay is performed using the MultiScreen 96-well plates. In short, the Caco-2 cells (ATCC, Cat. No HTB-37) are seeded into each well with a porous membrane bottom. The cells are grown for 20-23 days at 37°C in CO2 thermostat until total confluence. The growth medium is changed every 2-3 days. The physical integrity of the cell monolayer established on the well porous membrane is tested using a “leak test” with Lucifer Yellow CH. Permeability ofAVN-492 (200μM) is determined in both directions, the apical-to-basal and basal-to-apical. Permeabilities of comparison compounds Ranitidine (lowpermeability) and Propranolol (high permeability) are measured in apical-to-basal direction only. The Pgp-dependent permeability of Rhodamine 123 (30 μM) is determined with or without the Pgp inhibitor Verapamil (100 μM). To assess participation of the Pgp pump in a possible efflux of AVN-492, the apical-to-basal and basalto-apical permeabilities are also registered in the presence of Verapamil. Concentrations of AVN-322 in donor and acceptor chambers are determined using LC/MS/MS API2000. The apparent permeability is calculated[1]. |
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Animal experiment: |
Mice and Rats[1] For pharmacokinetic, behavior, and toxicity studies, male Wistar rats (220-242 g), male CD1 mice (24-30 g), male SHK mice (20-25 g), and male Balb/C mice (15-20 g) are used. The pharmacokinetic profiling of AVN-492 is performed on male CD-1 mice and male Wistar rats. Each dose-route group of rodents consist of 3 animals. AVN-492 is administered either intravenously (IV) or orally (PO). At different time points after the drug administration, the animals are quickly euthanized by placing them into CO2 chamber. Blood samples are drawn through a cardiopuncture. In separate experiments, AVN-492 is orally administered to male Wistar rats at doses of 1 mg/kg, 3 mg/kg, and 10 mg/kg (3 independent groups, 3 animals per group). The animals are anesthetized 60 min later with 5% halothane, positioned in a stereotaxic frame, and samples of cerebrospinal fluid (CSF) are taken through 23G needle from the cisterna magna. CSF samples are checked for the absence of blood contamination. After the CSF samples are taken, the blood samples are drawn through a cardiopuncture and the brains are removed, washed immediately with ice-cold saline, and homogenized in a 1:4 brain tissue/water mixture. AVN-492 is extracted from all the samples with acetonitrile and concentrations are determined using LC/MS/MS API2000. |
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References: [1]. Ivachtchenko AV, et al. AVN-492, A Novel Highly Selective 5-HT6R Antagonist: Preclinical Evaluation. J Alzheimers Dis. 2017;58(4):1043-1063. |
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| Cas No. | 1220646-23-0 | SDF | |
| Canonical SMILES | O=S(C1=CC=CC=C1)(C2=C3N(C(C)=C(N(C)C)C(C)=N3)N=C2NC)=O | ||
| Formula | C17H21N5O2S | M.Wt | 359.45 |
| الذوبان | DMSO : ≥ 100 mg/mL (278.20 mM) | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.782 mL | 13.9101 mL | 27.8203 mL |
| 5 mM | 0.5564 mL | 2.782 mL | 5.5641 mL |
| 10 mM | 0.2782 mL | 1.391 mL | 2.782 mL |
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Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
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3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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