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Purity: ≥98%
NS 1738 (also known as NSC 213859) is a novel and potent positive allosteric modulator of the α7 nAChR, with respect to positive modulation of nicotinic alpha7 receptor (α7 nAChR) with EC50 of 3.4 μM in oocyte experiments. NS1738 was unable to displace or affect radioligand binding to the agonist binding site of nicotinic receptors, and it was devoid of effect when applied alone in electrophysiological paradigms. However, when applied in the presence of acetylcholine (ACh), NS1738 produced a marked increase in the current flowing through alpha7 nAChRs, as determined in both oocyte electrophysiology and patch-clamp recordings from mammalian cells. NS1738 acted by increasing the peak amplitude of ACh-evoked currents at all concentrations; thus, it increased the maximal efficacy of ACh. Oocyte experiments indicated an increase in ACh potency as well. NS1738 had only marginal effects on the desensitization kinetics of alpha7 nAChRs, as determined from patch-clamp studies of both transfected cells and cultured hippocampal neurons. NS1738 was modestly brain-penetrant, and it was demonstrated to counteract a (-)-scopolamine-induced deficit in acquisition of a water-maze learning task in rats. Moreover, NS1738 improved performance in the rat social recognition test to the same extent as (-)-nicotine, demonstrating that NS1738 is capable of producing cognitive enhancement in vivo. These data support the notion that alpha7 nAChR allosteric modulation may constitute a novel pharmacological principle for the treatment of cognitive dysfunction.
| ln Vitro |
Acetylcholine (ACh)-evoked currents have a peak amplitude that NS 1738 rises at all doses, enhancing the maximum effectiveness of ACh. The preincubation NS 1738 concentration logarithm was plotted against the peak current amplitude, and the resulting concentration-response relationship was sigmoidal and well-fitted to the Hill equation (EC50=3.4 μM). Comparable efficacy and potency were demonstrated by NS 1738 against rat α7 nAChR (EC50=3.9 μM) in similar experimental circumstances [1].
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| ln Vivo |
Rats were given an intraperitoneal injection of 10 mg/kg of NS 1738 in order to evaluate its ability to cross the blood-brain barrier. At this dose, peak brain concentrations were measured about half an hour after injection, reaching about 80 ng/mL (approximately 200 nM). The ratio of the amount of compound entering the brain to the amount in the plasma is AUCbrain/AUCplasma=0.50, and the half-life in plasma is estimated to be 42 minutes. In vitro incubation of NS 1738 with isolated liver microsomes revealed that in mice and rats, respectively, approximately 60% and 75% of NS 1738 were metabolized by the cytochrome P450 system within an hour. Adult rats were injected with NS 1738 ip at 10 and 30 mg/kg immediately following the first exposure to juvenile rats (T1) and two hours later
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| References |
[1]. Timmermann DB, et al. An allosteric modulator of the alpha7 nicotinic acetylcholine receptor possessing cognition-enhancing properties in vivo. J Pharmacol Exp Ther. 2007 Oct;323(1):294-307
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| Molecular Formula |
C14H9CL2F3N2O2
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|---|---|
| Molecular Weight |
365.1347
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| CAS # |
501684-93-1
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| SMILES |
O=C(NC1=CC(Cl)=CC=C1O)NC2=CC(C(F)(F)F)=CC=C2Cl
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| InChi Key |
OUDXRNQPVSMGDW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H9Cl2F3N2O2/c15-8-2-4-12(22)11(6-8)21-13(23)20-10-5-7(14(17,18)19)1-3-9(10)16/h1-6,22H,(H2,20,21,23)
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| Chemical Name |
3-(5-chloro-2-hydroxyphenyl)-1-[2-chloro-5-(trifluoromethyl)phenyl]urea
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| Synonyms |
NSC 213859; NSC213859; NSC-213859; NS1738; NS 1738; NS-1738.
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ≥ 100 mg/mL (~273.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.85 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7388 mL | 13.6938 mL | 27.3875 mL | |
| 5 mM | 0.5478 mL | 2.7388 mL | 5.4775 mL | |
| 10 mM | 0.2739 mL | 1.3694 mL | 2.7388 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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