| Size | Price | Stock | Qty |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg | |||
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| Targets |
The primary target of NP118809 is the N-type calcium channel (CaV2.2), a voltage-gated calcium channel that is predominantly expressed in the central and peripheral nervous systems. N-type calcium channels are localized at presynaptic terminals, where they mediate the release of neurotransmitters, including substance P, glutamate, and calcitonin gene-related peptide (CGRP), which are involved in pain transmission. By inhibiting N-type calcium channels, NP118809 reduces neurotransmitter release, thereby attenuating pain signaling. The compound's selectivity for N-type over L-type and other calcium channel subtypes contributes to its specificity and reduced cardiovascular side effects.
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| 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].
In vitro, NP118809 is a potent and selective inhibitor of N-type calcium channels. Its activity is typically measured using electrophysiological recordings, such as patch-clamp techniques, in cells expressing N-type calcium channels. The compound's ability to inhibit N-type calcium currents is quantified by measuring the reduction in current amplitude in the presence of varying concentrations of the inhibitor. IC50 values are determined from dose-response curves. The compound's selectivity for N-type over L-type, P/Q-type, and T-type calcium channels is assessed to confirm its specificity. |
| 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].
In vivo, NP118809 has been studied for its analgesic effects in animal models of chronic pain. By inhibiting N-type calcium channels and reducing neurotransmitter release, the compound has been shown to produce significant pain relief in models of neuropathic pain, inflammatory pain, and postoperative pain. The compound's non-opioid mechanism of action makes it a potential alternative to opioid analgesics, with a reduced risk of addiction and respiratory depression. While specific in vivo efficacy data are not extensively detailed in the available literature, its mechanism of action supports its potential as an analgesic. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for NP118809 are not conventional enzyme inhibition studies, as the compound is an ion channel blocker rather than an enzyme inhibitor. Instead, the primary assays involve electrophysiological recordings using patch-clamp techniques in cells expressing N-type calcium channels. Radioligand binding studies using channel-specific ligands, such as radiolabeled ω-conotoxin GVIA, can also be performed to assess the compound's binding affinity. These assays confirm that NP118809 binds to and inhibits N-type calcium channels.
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| Cell Assay |
In vitro cellular assays for NP118809 are conducted in cell lines expressing N-type calcium channels, such as neuronal cell lines or HEK293 cells transfected with CaV2.2. Cells are treated with varying concentrations of NP118809, and calcium influx is measured using fluorescent calcium indicators or electrophysiological recordings. The compound's ability to inhibit N-type calcium currents is quantified. Neurotransmitter release assays are performed to assess the compound's effects on release of substance P, glutamate, or other neurotransmitters. These assays confirm that NP118809 engages its target in a cellular context and produces the expected inhibition of calcium influx and neurotransmitter release.
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| Animal Protocol |
In vivo animal studies for NP118809 are conducted in animal models of chronic pain, such as the spinal nerve ligation model, the complete Freund's adjuvant (CFA) model, or the formalin test. Animals are administered the compound orally or intraperitoneally, and pain behavior is assessed using von Frey filaments, thermal stimuli, or other pain tests. The compound's effects on motor function and cardiovascular parameters are also assessed. Pharmacokinetic studies are performed to determine the compound's bioavailability, half-life, and tissue distribution.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of NP118809 indicate that it has a molecular weight of 370.87 and a molecular formula of C23H23ClN2O. The compound is a small molecule with drug-like physicochemical properties. It is soluble in DMSO, facilitating its use in in vitro assays and formulation for in vivo administration. For storage, the powder should be kept under appropriate conditions to maintain stability. Its physicochemical properties suggest that it has reasonable drug-like characteristics for oral administration.
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| Toxicity/Toxicokinetics |
Toxicological information for NP118809 is primarily derived from its use as a research compound in preclinical studies. As an N-type calcium channel inhibitor, potential on-target effects include changes in neurotransmitter release, which could affect autonomic function and cognition. Cardiovascular effects, including hypotension and bradycardia, may also occur. Comprehensive toxicology studies would be required for therapeutic development, including assessments of neurological, cardiovascular, and autonomic function.
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| References | |
| Additional Infomation |
Z160 has been used in trials to study the treatment of postherpetic neuralgia and lumbosacral radiculopathy.
NP118809 is a potent and selective inhibitor of the N-type calcium channel (CaV2.2). It reduces neurotransmitter release and has analgesic effects in animal models of chronic pain. The compound is a non-opioid analgesic with potential for pain management. NP118809 is not approved for clinical use and is available from research chemical suppliers for preclinical studies. |
| Molecular Formula |
C32H32N2O
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|---|---|
| Molecular Weight |
460.621
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| Exact Mass |
460.251
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| CAS # |
41332-24-5
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| Related CAS # |
41332-24-5
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| PubChem CID |
4988454
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.1±0.1 g/cm3
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| Boiling Point |
618.9±55.0 °C at 760 mmHg
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| Flash Point |
251.4±23.9 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.622
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| LogP |
6.51
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
35
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| Complexity |
582
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VCPMZDWBEWTGNW-UHFFFAOYSA-N
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| 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
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| Chemical Name |
1-(4-benzhydrylpiperazin-1-yl)-3,3-diphenylpropan-1-one
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| Synonyms |
39-1B4 NP 118809 NP-118809 NP118809 Z160 Z160 Z160.
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~108.55 mM)
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| 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. View More
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. |
| 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.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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