Sofiniclin (formerly also known as ABT-894 and A-422894) is a novel and potent agonist of nicotinic acetylcholine receptor (nAChR) which is used as a potential non-stimulant treatment for attention-deficit/hyperactivity disorder (ADHD). Sofinicline is under development for the treatment of attention-deficit/hyperactivity disorder. Sofinicline appears to be well tolerated and showing efficacy similar to that of atomoxetine.

Physicochemical Properties

Molecular Formula	C10H11N3CL2
Molecular Weight	244.12044
Exact Mass	243.033
Elemental Analysis	C, 49.20; H, 4.54; Cl, 29.04; N, 17.21
CAS #	799279-80-4
Related CAS #	799279-87-1;799279-85-9 (tartrate);869792-84-7 (acetate);869792-87-0 (mesylate); 869792-90-5 (HCl); 799279-80-4; 876170-44-4 (besylate);
PubChem CID	10131048
Appearance	Off-white to brown solid powder
LogP	2.19
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	3
Rotatable Bond Count	1
Heavy Atom Count	15
Complexity	251
Defined Atom Stereocenter Count	2
SMILES	ClC1C(Cl)=NC=C(N2C[C@H]3NC[C@H]3C2)C=1
InChi Key	MBQYQLWSBRANKQ-IMTBSYHQSA-N
InChi Code	InChI=1S/C10H11Cl2N3/c11-8-1-7(3-14-10(8)12)15-4-6-2-13-9(6)5-15/h1,3,6,9,13H,2,4-5H2/t6-,9+/m0/s1
Chemical Name	(1S,5S)-3-(5,6-dichloropyridin-3-yl)-3,6-diazabicyclo[3.2.0]heptane
Synonyms	Sofinicline; ABT-894; A-422894.0; ABT 894; A-422894; ABT894; A 422894.0
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
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	With Ki values of 1.3 nM for 125I-epibatidine binding and 1.9 nM for 125I-α-conotoxinMII binding, sofiniclin is more potent than ABT-089 at both receptor subtypes[1].
ln Vivo	Compared to a vehicle monkey, sofiniclin (0.001 to 0.10 mg/kg, po) significantly lowers LIDs[1]. Monkeys with extensive nigrostriatal injury do not have a reduction in LIDs when given sofiniclin (0.1 mg/kg)[2].
References	[1]. ABT-089 and ABT-894 reduce levodopa-induced dyskinesias in a monkey model of Parkinson's disease. Mov Disord. 2014 Apr;29(4):508-17. [2]. α7 nicotinic receptor agonists reduce levodopa-induced dyskinesias with severe nigrostriatal damage. Mov Disord. 2015 Dec;30(14):1901-11.
Additional Infomation	Sofinicline has been used in trials studying the treatment of ADHD, Neuralgia, Diabetic, Diabetic Neuropathies, Diabetic Polyneuropathy, and Diabetic Neuropathic Pain, among others.

Solubility Data

Solubility (In Vitro)

DMSO : ~35.71 mg/mL (~146.28 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.08 mg/mL (8.52 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 20.8 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: ≥ 2.08 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 20.8 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. Solubility in Formulation 3: ≥ 2.08 mg/mL (8.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.0963 mL	20.4817 mL	40.9635 mL
	5 mM	0.8193 mL	4.0963 mL	8.1927 mL
	10 mM	0.4096 mL	2.0482 mL	4.0963 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.