NS 1738 (NSC 213859) is a novel positive allosteric modulator of the α7 nAChR, with respect to positive modulation of α7 nAChR (EC50=3.4 μM in oocyte experiments).

Product information

CAS Number: 501684-93-1

Molecular Weight: 365.13

Formula: C14H9Cl2F3N2O2

Chemical Name: 1-(5-chloro-2-hydroxyphenyl)-3-[2-chloro-5-(trifluoromethyl)phenyl]urea

Smiles: OC1=CC=C(Cl)C=C1NC(=O)NC1=CC(=CC=C1Cl)C(F)(F)F

InChiKey: OUDXRNQPVSMGDW-UHFFFAOYSA-N

InChi: 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)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO : ≥ 100 mg/mL (273.88 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

NS 1738 acts by increasing the peak amplitude of acetylcholine (ACh)-evoked currents at all concentrations; thus, it increased the maximal efficacy of ACh. Plotting peak current amplitude against the logarithm of the NS 1738 concentration used for preincubation reveals a sigmoidal concentration-response relationship that is well fit by the Hill equation (EC50=3.4 μM). Under similar experimental conditions, NS 1738 shows comparable efficacy and potency at the rat α7 nAChR (EC50=3.9 μM).

In Vivo:

To estimate the ability of NS 1738 to permeate the blood-brain barrier, rats are administered 10 mg/kg NS 1738 intraperitoneally. Peak brain concentrations are measured approximately 30 min after injection, and they amount to ~80 ng/mL (~200 nM) at this dose. The ratio between the amount of compound entering the brain and that in plasma is AUCbrain /AUCplasma=0.50. The half-life in plasma is estimated to 42 min. Incubation of NS1738 with isolated liver microsomes in vitro indicates that approximately 60 and 75% of NS 1738 is metabolized via the cytochrome P450 system in mouse and rat, respectively, within 1 h. Adult rats administered NS 1738 at 10 and 30 mg/kg i.p. immediately following the initial exposure to a juvenile rat (T1) display significant decreases in the investigative duration of a subsequent exposure to the same juvenile (T2) 2 h later (T2/T1 ratio of 0.69±0.13 and 0.61±0.07, respectively).

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.

Products are for research use only. Not for human use.