Bradanicline is a selective α7 nicotinic acetylcholine receptor (nAChR) agonist (EC50=17 nM; Ki= 1.4 nM for human α7 nAChR). Bradanicline may be utilized to study cognitive impairment.

Physicochemical Properties

Molecular Formula	C22H23N3O2
Molecular Weight	361.44
Exact Mass	361.179
CAS #	639489-84-2
PubChem CID	25147644
Appearance	White to off-white solid powder
LogP	3.775
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	4
Heavy Atom Count	27
Complexity	534
Defined Atom Stereocenter Count	2
SMILES	C1CN2CCC1[C@H]([C@@H]2CC3=CN=CC=C3)NC(=O)C4=CC5=CC=CC=C5O4
InChi Key	OXKRFEWMSWPKKV-GHTZIAJQSA-N
InChi Code	InChI=1S/C22H23N3O2/c26-22(20-13-17-5-1-2-6-19(17)27-20)24-21-16-7-10-25(11-8-16)18(21)12-15-4-3-9-23-14-15/h1-6,9,13-14,16,18,21H,7-8,10-12H2,(H,24,26)/t18-,21+/m0/s1
Chemical Name	N-[(2S,3R)-2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]octan-3-yl]-1-benzofuran-2-carboxamide
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	Bradanicline exhibits a notable preference for the central nervous system over the peripheral nervous system, as evidenced by the more than a thousand-fold gap in affinities between the α7 and α4β2 receptor subtypes and the lack of any discernible effects on muscular or ganglionic nicotinic receptor subtypes[1].
ln Vivo	In animal models of positive and negative symptoms as well as cognitive impairment associated with schizophrenia, bradanicline (0.1–1 mg/kg) demonstrates efficacy[2].
References	[1]. Discovery of (2S,3R)-N-[2-(pyridin-3-ylmethyl)-1-azabicyclo[2.2.2]oct-3-yl]benzo[b]furan-2-carboxamide (TC-5619), a selective α7 nicotinic acetylcholine receptor agonist, for the treatment of cognitive disorders. J Med Chem. 2012;55(22). [2]. TC-5619: an alpha7 neuronal nicotinic receptor-selective agonist that demonstrates efficacy in animal models of the positive and negative symptoms and cognitive dysfunction of schizophrenia. Biochem Pharmacol. 2009;78(7):803-812.
Additional Infomation	Bradanicline, a novel small molecule that modulates the activity of the neuronal nicotinic receptor (NNR) subtype known as alpha7(α7). Bradanicline belongs to a new class of drugs for the treatment of central nervous system diseases and disorders. Drug Indication Investigated for use/treatment in neurologic disorders. Mechanism of Action Bradanicline, a novel small molecule that modulates the activity of the neuronal nicotinic receptor (NNR) subtype known as alpha7(α7). The α7 NNR is associated with a variety of biological functions. In particular, the α7 NNR has been shown in animal studies to be an essential regulator of both inflammation arising from injury or infection and cognitive functions. α7 NNR plays a role in protecting neuronal cells from deterioration and death, a process known as neuroprotection.

Solubility Data

Solubility (In Vitro)

DMSO: 25 mg/mL (69.17 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 2.5 mg/mL (6.92 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 (6.92 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 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. Solubility in Formulation 3: ≥ 2.5 mg/mL (6.92 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 25.0 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	2.7667 mL	13.8336 mL	27.6671 mL
	5 mM	0.5533 mL	2.7667 mL	5.5334 mL
	10 mM	0.2767 mL	1.3834 mL	2.7667 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.