CP-601932 ((1S,5R)-CP-601927) is a high-affinity partial agonist of α3β4 nAChR (Ki=21; EC50=~3 μM). CP-601932 has the same high binding affinity for α3β4 and α4β2 nAChRs, with an order of magnitude lower affinity for α6 and α7 nAChR isoforms. CP-601932 selectively reduces ethanol consumption but not sucrose consumption and operant self-administration after long-term exposure. CP-601932 penetrates the BBB (blood-brain barrier).

Physicochemical Properties

Molecular Formula	C12H12F3N
Molecular Weight	227.225593566895
Exact Mass	227.092
CAS #	357425-68-4
Related CAS #	CP-601927;357425-02-6;(Rac)-CP-601927 hydrochloride;230615-01-7
PubChem CID	69604735
Appearance	Light yellow to light brown ointment
LogP	2.4
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	4
Rotatable Bond Count	0
Heavy Atom Count	16
Complexity	276
Defined Atom Stereocenter Count	2
SMILES	C1[C@@H]2CNC[C@H]1C3=C2C=CC(=C3)C(F)(F)F
InChi Key	RNOBTWYQAWEZHH-SFYZADRCSA-N
InChi Code	InChI=1S/C12H12F3N/c13-12(14,15)9-1-2-10-7-3-8(6-16-5-7)11(10)4-9/h1-2,4,7-8,16H,3,5-6H2/t7-,8+/m1/s1
Chemical Name	(1R,8S)-4-(trifluoromethyl)-10-azatricyclo[6.3.1.02,7]dodeca-2(7),3,5-triene
Synonyms	CP601932; CP 601932; CP-601932
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 Vivo

CP-601932 (10 mg/kg; subcutaneous injection; adult male Sprague-Dawley rats) lowers active lever pressure for 10% ethanol but not for 5% sucrose in an operant self-administration paradigm [1] . CP-601932 (adult male Sprague-Dawley rats) easily penetrates the CNS and reaches maximum Cb,u values of 340 nM at 30 minutes after the 5 mg/kg dosage and 710 nM after the 10 mg/kg treatment. Brain concentrations of CP-601932 fall extremely slowly and levels remain reasonably high, such as 530 nM at 5 hours and 85 nM at 24 hours after 10 mg/kg [1].

References

[1]. Partial agonists of the α3β4* neuronal nicotinic acetylcholine receptor reduce ethanol consumption and seeking in rats. Neuropsychopharmacology. 2011;36(3):603-615.

Solubility Data

Solubility (In Vitro)

DMSO : ~200 mg/mL (~880.17 mM)

Solubility (In Vivo)

Solubility in Formulation 1: ≥ 5 mg/mL (22.00 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 50.0 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: ≥ 5 mg/mL (22.00 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 50.0 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.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	4.4008 mL	22.0041 mL	44.0083 mL
	5 mM	0.8802 mL	4.4008 mL	8.8017 mL
	10 mM	0.4401 mL	2.2004 mL	4.4008 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.