A-867744 |
| Catalog No.GC15014 |
A positive allosteric modulator of α7 nAChRs
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1000279-69-5
Sample solution is provided at 25 µL, 10mM.
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Targeting α7 neuronal acetylcholine receptors (nAChRs) with selective agonists and positive allosteric modulators (PAMs) is considered a therapeutic approach for managing cognitive deficits in schizophrenia and Alzheimer's disease. A-867744 is a novel type II PAM with good potency and selectivity.
In vitro: In oocytes expressing α7 nAChRs, A-867744 potentiated acetylcholine (ACh)-evoked currents, with an EC50 value of about 1 μM. At highest concentrations of A-867744 tested, ACh-evoked currents were essentially nondecaying. At lower concentrations, no evidence of a distinct secondary component was evident in contrast to 4-naphthalen-1-yl-3a,4,5,9b-tetrahydro -3H-cyclopent-a[c]quinoline-8-sulfonic acid amide (TQS), another type II α7 PAM [1].
In vivo: A-867744 was assessed for its PK properties in rat, dog, and monkey. The animal pharmacokinetic profile of A-867744 was characterized by relatively low plasma clearance values (1.1-2.5 L/h/kg) and volumes of distribution (1.7-4.6 L/kg) across species, with terminal elimination halflives in the 1.0-1.7 h. The bioavailability is 83% in rat and somewhat lower in dog (55%) and monkey (68%). These findings indicated that A-867744 showed acceptable pharmacokinetic profile across species and brain levels sufficient to modulate α7 nAChRs [2].
Clinical trial: A-867744 is currently in the preclinical developlent stage and no clinical data are available.
Reference:
[1] Malysz J, Grønlien JH, Anderson DJ, Håkerud M, Thorin-Hagene K, Ween H, Wetterstrand C, Briggs CA, Faghih R, Bunnelle WH, Gopalakrishnan M.
In vitro pharmacological characterization of a novel allosteric modulator of alpha 7 neuronal acetylcholine receptor, 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl) (A-867744), exhibiting unique pharmacological profile. J Pharmacol Exp Ther. 2009;330(1):257-67.
[2] Faghih R, Gopalakrishnan SM, Gronlien JH, Malysz J, Briggs CA, Wetterstrand C, Ween H, Curtis MP, Sarris KA, Gfesser GA, El-Kouhen R, Robb HM, Radek RJ, Marsh KC, Bunnelle WH, Gopalakrishnan M. Discovery of 4-(5-(4-chlorophenyl)-2-methyl-3-propionyl-1H-pyrrol-1-yl) benzenesulfonamide (A-867744) as a novel positive allosteric modulator of the alpha7 nicotinic acetylcholine receptor. J Med Chem. 2009;52(10):3377-84.
| Cas No. | 1000279-69-5 | SDF | |
| Chemical Name | 4-[5-(4-chlorophenyl)-2-methyl-3-propanoylpyrrol-1-yl]benzenesulfonamide | ||
| Canonical SMILES | CCC(=O)C1=C(N(C(=C1)C2=CC=C(C=C2)Cl)C3=CC=C(C=C3)S(=O)(=O)N)C | ||
| Formula | C20H19ClN2O3S | M.Wt | 402.89 |
| Solubility | DMF: 30 mg/ml,DMF:PBS (pH 7.2) (1:4): 0.20 mg/ml,DMSO: 10 mg/ml | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 2.4821 mL | 12.4103 mL | 24.8207 mL |
| 5 mM | 0.4964 mL | 2.4821 mL | 4.9641 mL |
| 10 mM | 0.2482 mL | 1.241 mL | 2.4821 mL |
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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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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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