Pozanicline diHCl (ABT-089 diHCl) is an orally bioactive nicotinic acetylcholine receptor (nAChR) agonist that binds to the [3H] cystine site with Ki of 16.7 nM. Pozanicline diHCl is an α4β2-selective nAChR agonist that binds to rat brain α4β2 nAChR with Ki of 17 nM and binds only weakly to α7nAChR.

Physicochemical Properties

Molecular Formula	C11H18CL2N2O
Molecular Weight	265.179420948029
Exact Mass	264.079
CAS #	161416-61-1
Related CAS #	Pozanicline;161417-03-4
PubChem CID	23729426
Appearance	White to off-white solid powder
Hydrogen Bond Donor Count	3
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	3
Heavy Atom Count	16
Complexity	175
Defined Atom Stereocenter Count	1
SMILES	CC1=C(C=CC=N1)OC[C@@H]2CCCN2.Cl.Cl
InChi Key	UGVSESCRKJTJAK-XRIOVQLTSA-N
InChi Code	InChI=1S/C11H16N2O.2ClH/c1-9-11(5-3-6-12-9)14-8-10-4-2-7-13-10;;/h3,5-6,10,13H,2,4,7-8H2,1H3;2*1H/t10-;;/m0../s1
Chemical Name	2-methyl-3-[[(2S)-pyrrolidin-2-yl]methoxy]pyridine;dihydrochloride
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	ABT-089. Pozanicline is a partial agonist that acts on the α4β2 nAChR. Furthermore, with an EC50 of 0.11 μM, one α6β2 nAChR isoform is extremely sensitive to pozanicline [2]. The nAChR isoforms α6β2 and α4α5β2 are highly selective for pazanicline (ABT-089) [3].
ln Vivo	Deficits in contextual fear conditioning brought on by nicotine withdrawal are corrected by pozanicline (ABT-089; 0.3 mg/kg and 0.6 mg/kg) [3].
Animal Protocol	Animal/Disease Models: 8-12 weeks old adult male C57BL6/J mice [3]. Doses: 0.3 mg/kg and 0.6 mg/kg Route of Administration: Treatment was administered 5 minutes before training and testing contextual fear conditioning Experimental Results: Doses of 0.3 mg/kg and 0.6 mg/kg improved nicotine withdrawal-induced contextual fear conditioning aware of defects.
References	[1]. Structure-activity studies on 2-methyl-3-(2(S)-pyrrolidinylmethoxy) pyridine (ABT-089): an orally bioavailable 3-pyridyl ether nicotinic acetylcholine receptor ligand with cognition-enhancing properties. J Med Chem. 1997 Jan 31;40(3):385-90. [2]. Selectivity of ABT-089 for α4β2 and α6β2 nicotinic acetylcholine receptors in brain. Biochem Pharmacol. 2009 Oct 1;78(7):795-802. [3]. ABT-089, but not ABT-107, ameliorates nicotine withdrawal-induced cognitive deficits in C57BL6/J mice. Behav Pharmacol. 2015 Apr;26(3):241-8.

Solubility Data

Solubility (In Vitro)	H2O : ~100 mg/mL (~377.10 mM)
Solubility (In Vivo)	Solubility in Formulation 1: 100 mg/mL (377.10 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	3.7710 mL	18.8551 mL	37.7102 mL
	5 mM	0.7542 mL	3.7710 mL	7.5420 mL
	10 mM	0.3771 mL	1.8855 mL	3.7710 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.