NP-118809 is a N-type calcium channel blocker. NP-118809 exhibits both anti-allodynic and anti-hyperalgesic activity in the spinal nerve ligation model of neuropathic pain. NP118809 further exhibits a number of favorable preclinical characteristics as they relate to overall pharmacokinetics and minimal off-target activity including the hERG potassium channel.

Physicochemical Properties

Molecular Formula	C32H32N2O
Molecular Weight	460.621
Exact Mass	460.251
CAS #	41332-24-5
Related CAS #	41332-24-5
PubChem CID	4988454
Appearance	Light yellow to yellow solid powder
Density	1.1±0.1 g/cm3
Boiling Point	618.9±55.0 °C at 760 mmHg
Flash Point	251.4±23.9 °C
Vapour Pressure	0.0±1.8 mmHg at 25°C
Index of Refraction	1.622
LogP	6.51
Hydrogen Bond Donor Count	0
Hydrogen Bond Acceptor Count	2
Rotatable Bond Count	7
Heavy Atom Count	35
Complexity	582
Defined Atom Stereocenter Count	0
InChi Key	VCPMZDWBEWTGNW-UHFFFAOYSA-N
InChi Code	InChI=1S/C32H32N2O/c35-31(25-30(26-13-5-1-6-14-26)27-15-7-2-8-16-27)33-21-23-34(24-22-33)32(28-17-9-3-10-18-28)29-19-11-4-12-20-29/h1-20,30,32H,21-25H2
Chemical Name	1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one
Synonyms	39-1B4 NP 118809 NP-118809 NP118809 Z160 Z160 Z160.
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	NP118809 has a strong inhibitory effect on N-type calcium channels, having an IC50 of 0.11 μM, and an IC50 of 12.2 μM on L-type calcium channels. In HEK cells, NP118809 blocks hERG potassium channels with an IC50 of 7.4 μM[1].
ln Vivo	The rat formalin model's phase IIA section demonstrated notable analgesic action in response to NP118809 (25 mg/kg, i.p.) [1]. NP118809 (30 mg/kg, orally) reduced 96.3% of thermal hyperalgesia and 80.3% of mechanical allodynia in a rat spinal nerve ligation model [2].
References	[1]. Scaffold-based design and synthesis of potent N-type calcium channel blockers. Bioorg Med Chem Lett. 2009 Nov 15;19(22):6467-72. [2]. Structure-activity relationships of diphenylpiperazine N-type calcium channel inhibitors. Bioorg Med Chem Lett. 2010 Feb 15;20(4):1378-83.
Additional Infomation	Z160 has been used in trials studying the treatment of Postherpetic Neuralgia and Lumbosacral Radiculopathy.

Solubility Data

Solubility (In Vitro)

DMSO : ~50 mg/mL (~108.55 mM)

Solubility (In Vivo)

Solubility in Formulation 1: 2.5 mg/mL (5.43 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with heating and sonication. 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 (5.43 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 (5.43 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	2.1710 mL	10.8549 mL	21.7099 mL
	5 mM	0.4342 mL	2.1710 mL	4.3420 mL
	10 mM	0.2171 mL	1.0855 mL	2.1710 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.