NS9283 | CAS#913830-15-6 | α4β2 Nicotonic Receptor

NS9283
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WARNING: This product is for research use only, not for human or veterinary use.

MedKoo CAT#: 532373

CAS#: 913830-15-6

Description: NS9283 is a positive allosteric modulator of α4β2 receptor. NS9283 increases the potency of Ach-evoked currents ~60 fold without effecting the maximum efficacy (HEK293-hα4β2 cells). It reduces the rate of recovery from desensitization and slows the rate of deactivation.

Chemical Structure

NS9283

CAS# 913830-15-6

Product data Instruction

Theoretical Analysis

MedKoo Cat#: 532373
Name: NS9283
CAS#: 913830-15-6
Chemical Formula: C14H8N4O
Exact Mass: 248.07
Molecular Weight: 248.245
Elemental Analysis: C, 67.74; H, 3.25; N, 22.57; O, 6.44

Price and Availability

Size	Price	Availability	Quantity
10mg	USD 330
25mg	USD 630
Bulk inquiry Welcome, Customer: Please do not inquire quote if your intended use is for a patient since our products are for research use and for chemical synthesis use, not for human use . For in-stock products, we listed price in the web page. You may inquire prices for which sizes were not listed. If no price is listed, this means the product is not in stock at the moment, which may be available via custom synthesis. For cost-effective reason, minimum order of 1g is requested (typically very expensive). The lead time is usually 2-4 months. Quote of less than 1g will not be provided. MedKoo may not offer quote for below reasons: (1) current available synthetic method appears to be extremely expensive which is obviously not affordable to most customers; (2) Key raw material to make the product is temporally not available; (3) DEA controlled substances; (4) the product is under patent protection in customer’s country.

Synonym: NS9283; NS 9283; NS-9283.

IUPAC/Chemical Name: 3-[3-(pyridin-3-yl)-1,2,4-oxadiazol-5-yl]benzonitrile

InChi Key: HGFXDSQLRSWUBO-UHFFFAOYSA-N

InChi Code: InChI=1S/C14H8N4O/c15-8-10-3-1-4-11(7-10)14-17-13(18-19-14)12-5-2-6-16-9-12/h1-7,9H

SMILES Code: N#CC1=CC=CC(C2=NC(C3=CC=CN=C3)=NO2)=C1

Appearance: Solid powder

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

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Product Data:

Product Data

Instruction:

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Biological target:	NS9283 is a positive positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors.
In vitro activity:	NS9283 was demonstrated to increase the potency of ACh-evoked currents in HEK293-hα4β2 cells by left-shifting the concentration-response curve ~60-fold. Interestingly, this modulation did not significantly alter maximal efficacy levels of ACh. NS9283 strongly decreased the rate of deactivation kinetics and also modestly decreased the rate of activation. This resulted in a left-shift of the ACh window current of (α4)3(β2)2 nAChRs in the presence of NS9283. Reference: Br J Pharmacol. 2013 Apr;168(8):2000-10. https://pubmed.ncbi.nlm.nih.gov/23278456/
In vivo activity:	The present experiments tested the nicotine discriminative-stimulus effects of the α4β2* PAM NS9283 (A-969933) in the presence and absence of low-dose nicotine or nicotinic subtype-selective agonist. Rats were trained to discriminate 0.4 mg/kg nicotine from saline in a two-lever drug discrimination paradigm. In subsequent generalization tests, rats were administered nicotine, the α4β2*-preferring agonist ABT-594, and NS9283, alone or in two-drug combinations. Nicotine and ABT-594 showed dose-dependent nicotine generalization. NS9283 alone resulted in a non-significant increase in nicotine-appropriate lever selection. Combination of non-effective doses of nicotine or ABT-594 with escalating doses of NS9283 resulted in a complete conversion to 100 % nicotine-appropriate choice in the case of nicotine combination and incomplete, though significant, generalization for ABT-594. Reference: Psychopharmacology (Berl). 2014 Jan;231(1):67-74. https://pubmed.ncbi.nlm.nih.gov/23925734/

Solubility Data

	Solvent	Max Conc. mg/mL	Max Conc. mM
Solubility
	DMF	10.0	40.28
	DMF:PBS (pH 7.2) (1:1)	0.5	2.01
	DMSO	7.7	31.04

Preparing Stock Solutions

The following data is based on the product molecular weight 248.25 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:	1. Olsen JA, Kastrup JS, Peters D, Gajhede M, Balle T, Ahring PK. Two distinct allosteric binding sites at α4β2 nicotinic acetylcholine receptors revealed by NS206 and NS9283 give unique insights to binding activity-associated linkage at Cys-loop receptors. J Biol Chem. 2013 Dec 13;288(50):35997-6006. doi: 10.1074/jbc.M113.498618. Epub 2013 Oct 29. PMID: 24169695; PMCID: PMC3861648. 2. Grupe M, Jensen AA, Ahring PK, Christensen JK, Grunnet M. Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors. Br J Pharmacol. 2013 Apr;168(8):2000-10. doi: 10.1111/bph.12095. PMID: 23278456; PMCID: PMC3623068. 3. Wang J, Blasio A, Chapman HL, Doebelin C, Liaw V, Kuryatov A, Giovanetti SM, Lindstrom J, Lin L, Cameron MD, Kamenecka TM, Pomrenze MB, Messing RO. Promoting activity of (α4)3(β2)2 nicotinic cholinergic receptors reduces ethanol consumption. Neuropsychopharmacology. 2020 Jan;45(2):301-308. doi: 10.1038/s41386-019-0475-8. Epub 2019 Aug 8. PMID: 31394567; PMCID: PMC6901472. 4. Mohler EG, Franklin SR, Rueter LE. Discriminative-stimulus effects of NS9283, a nicotinic α4β2* positive allosteric modulator, in nicotine-discriminating rats. Psychopharmacology (Berl). 2014 Jan;231(1):67-74. doi: 10.1007/s00213-013-3207-5. Epub 2013 Aug 8. PMID: 23925734.
In vitro protocol:	1. Olsen JA, Kastrup JS, Peters D, Gajhede M, Balle T, Ahring PK. Two distinct allosteric binding sites at α4β2 nicotinic acetylcholine receptors revealed by NS206 and NS9283 give unique insights to binding activity-associated linkage at Cys-loop receptors. J Biol Chem. 2013 Dec 13;288(50):35997-6006. doi: 10.1074/jbc.M113.498618. Epub 2013 Oct 29. PMID: 24169695; PMCID: PMC3861648. 2. Grupe M, Jensen AA, Ahring PK, Christensen JK, Grunnet M. Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors. Br J Pharmacol. 2013 Apr;168(8):2000-10. doi: 10.1111/bph.12095. PMID: 23278456; PMCID: PMC3623068.
In vivo protocol:	1. Wang J, Blasio A, Chapman HL, Doebelin C, Liaw V, Kuryatov A, Giovanetti SM, Lindstrom J, Lin L, Cameron MD, Kamenecka TM, Pomrenze MB, Messing RO. Promoting activity of (α4)3(β2)2 nicotinic cholinergic receptors reduces ethanol consumption. Neuropsychopharmacology. 2020 Jan;45(2):301-308. doi: 10.1038/s41386-019-0475-8. Epub 2019 Aug 8. PMID: 31394567; PMCID: PMC6901472. 2. Mohler EG, Franklin SR, Rueter LE. Discriminative-stimulus effects of NS9283, a nicotinic α4β2* positive allosteric modulator, in nicotine-discriminating rats. Psychopharmacology (Berl). 2014 Jan;231(1):67-74. doi: 10.1007/s00213-013-3207-5. Epub 2013 Aug 8. PMID: 23925734.

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1: Maurer JJ, Sandager-Nielsen K, Schmidt HD. Attenuation of nicotine taking and seeking in rats by the stoichiometry-selective alpha4beta2 nicotinic acetylcholine receptor positive allosteric modulator NS9283. Psychopharmacology (Berl). 2017 Feb;234(3):475-484. doi: 10.1007/s00213-016-4475-7. Epub 2016 Nov 14. PubMed PMID: 27844094.

2: Olsen JA, Ahring PK, Kastrup JS, Gajhede M, Balle T. Structural and functional studies of the modulator NS9283 reveal agonist-like mechanism of action at α4β2 nicotinic acetylcholine receptors. J Biol Chem. 2014 Sep 5;289(36):24911-21. doi: 10.1074/jbc.M114.568097. Epub 2014 Jun 30. PubMed PMID: 24982426; PubMed Central PMCID: PMC4155659.

3: Grupe M, Grunnet M, Laursen B, Bastlund JF. Neuropharmacological modulation of the P3-like event-related potential in a rat two-tone auditory discrimination task with modafinil and NS9283, a positive allosteric modulator of α4β2 nAChRs. Neuropharmacology. 2014 Apr;79:444-55. doi: 10.1016/j.neuropharm.2013.12.008. Epub 2013 Dec 17. PubMed PMID: 24361451.

4: Olsen JA, Kastrup JS, Peters D, Gajhede M, Balle T, Ahring PK. Two distinct allosteric binding sites at α4β2 nicotinic acetylcholine receptors revealed by NS206 and NS9283 give unique insights to binding activity-associated linkage at Cys-loop receptors. J Biol Chem. 2013 Dec 13;288(50):35997-6006. doi: 10.1074/jbc.M113.498618. Epub 2013 Oct 29. PubMed PMID: 24169695; PubMed Central PMCID: PMC3861648.

5: Mohler EG, Franklin SR, Rueter LE. Discriminative-stimulus effects of NS9283, a nicotinic α4β2* positive allosteric modulator, in nicotine-discriminating rats. Psychopharmacology (Berl). 2014 Jan;231(1):67-74. doi: 10.1007/s00213-013-3207-5. Epub 2013 Aug 8. PubMed PMID: 23925734.

6: Grupe M, Jensen AA, Ahring PK, Christensen JK, Grunnet M. Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors. Br J Pharmacol. 2013 Apr;168(8):2000-10. doi: 10.1111/bph.12095. PubMed PMID: 23278456; PubMed Central PMCID: PMC3623068.

7: Timmermann DB, Sandager-Nielsen K, Dyhring T, Smith M, Jacobsen AM, Nielsen EØ, Grunnet M, Christensen JK, Peters D, Kohlhaas K, Olsen GM, Ahring PK. Augmentation of cognitive function by NS9283, a stoichiometry-dependent positive allosteric modulator of α2- and α4-containing nicotinic acetylcholine receptors. Br J Pharmacol. 2012 Sep;167(1):164-82. doi: 10.1111/j.1476-5381.2012.01989.x. PubMed PMID: 22506660; PubMed Central PMCID: PMC3448921.

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