| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
NK-1 receptor (neurokinin-1 receptor).
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|---|---|
| ln Vitro |
NKP-608 is a potent antagonist at the neurokinin-1 (NK-1) receptor with an IC50 of 2.6 nM in vitro. It has anxiolytic action in the social interaction test in rats. The compound inhibits substance P (SP)-induced airway plasma protein exudation in vivo. NKP-608 has anticancer and anti-anxiety activities, and inhibits the proliferation of human colorectal cancer cells through the Wnt signaling pathway. It has been explored in preclinical research for cardiovascular and ocular indications.
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| ln Vivo |
NKP-608 has anxiolytic action in the social interaction test in rats. It inhibits substance P (SP)-induced airway plasma protein exudation in vivo. The compound has been explored in preclinical research for cardiovascular and ocular indications, including hypertension-related vascular dysfunction and intraocular pressure control. By suppressing ROCK activity, NKP-608 promotes vasodilation, reduces cellular contractility, and modulates inflammatory and fibrotic responses.
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| Enzyme Assay |
The in vitro receptor binding assay for NK-1 receptor antagonism uses membrane preparations from cells expressing recombinant human NK-1 receptor or from native tissues. NKP-608 is incubated with the receptor preparation and a radiolabeled NK-1 receptor ligand (e.g., [3H]substance P) at varying concentrations (typically 0.01 nM to 100 µM). After incubation, bound and free radioactivity are separated by filtration. The IC50 or Ki value is calculated from competition binding curves. Selectivity is assessed by profiling against other neurokinin receptors (NK-2, NK-3) and related GPCRs.
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| Cell Assay |
In vitro cellular assays are performed using cells expressing the NK-1 receptor (e.g., U373MG astrocytoma cells or recombinant cell lines). Cells are pre-incubated with NKP-608 at concentrations ranging from 0.01 nM to 100 µM for 30-60 minutes, followed by stimulation with substance P. Intracellular calcium mobilization is measured using calcium-sensitive fluorescent dyes (e.g., Fluo-4). The IC50 for inhibition of substance P-induced calcium flux is calculated. For anticancer activity, human colorectal cancer cells are treated with NKP-608 and cell proliferation is measured by MTT or BrdU incorporation assays. Wnt signaling pathway activity is assessed by measuring β-catenin levels or TOPFlash reporter activity.
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| Animal Protocol |
In vivo efficacy is evaluated in rat models of anxiety using the social interaction test. Rats are administered NKP-608 (oral or intraperitoneal) and social interaction time is measured. For airway inflammation models, substance P-induced plasma protein exudation is measured in guinea pigs or rats following NKP-608 administration. Evans blue dye is administered intravenously, and extravasation into airway tissues is measured spectrophotometrically. For ocular studies, intraocular pressure is measured following compound administration.
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| ADME/Pharmacokinetics |
NKP-608 has a molecular weight of approximately 550 g/mol and is a non-peptidic 4-aminopiperidine derivative. It is orally bioavailable and centrally active. The compound is soluble in DMSO and should be stored as a powder at -20°C. Pharmacokinetic parameters such as oral bioavailability, plasma half-life, and brain penetration have been characterized in preclinical studies. The compound is typically formulated for oral or parenteral administration.
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| Toxicity/Toxicokinetics |
No detailed toxicity data is publicly available for NKP-608. As a research compound, it is not intended for human use and has not undergone formal toxicological evaluation. Standard preclinical safety assessments for NK-1 receptor antagonists would typically include selectivity profiling against a panel of receptors and ion channels, hERG channel inhibition for cardiac safety, and CYP450 enzyme inhibition for drug-drug interaction potential. The compound is for research use only.
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| References |
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| Additional Infomation |
NKP-608 is a research-grade NK-1 receptor antagonist with anxiolytic and anticancer activities. It is not approved for clinical use. The compound is a non-peptidic derivative of 4-aminopiperidine. It inhibits substance P-induced responses and has been explored for cardiovascular and ocular indications. NKP-608 inhibits colorectal cancer cell proliferation through the Wnt signaling pathway. It is supplied as a solid with high purity and should be stored desiccated at -20°C.
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| Molecular Formula |
C31H24CLF6N3O2
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|---|---|
| Molecular Weight |
619.9924
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| Exact Mass |
619.146
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| CAS # |
177707-12-9
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| PubChem CID |
9917079
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| Appearance |
Light yellow to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
719.2±60.0 °C at 760 mmHg
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| Flash Point |
388.8±32.9 °C
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| Vapour Pressure |
0.0±2.3 mmHg at 25°C
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| Index of Refraction |
1.614
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| LogP |
6.74
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
43
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| Complexity |
950
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1CN([C@@H](C[C@H]1NC(=O)C2=CC=NC3=CC=CC=C23)CC4=CC=C(C=C4)Cl)C(=O)C5=CC(=CC(=C5)C(F)(F)F)C(F)(F)F
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| InChi Key |
NXLUTEDAEFXMQR-BJKOFHAPSA-N
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| InChi Code |
InChI=1S/C31H24ClF6N3O2/c32-22-7-5-18(6-8-22)13-24-17-23(40-28(42)26-9-11-39-27-4-2-1-3-25(26)27)10-12-41(24)29(43)19-14-20(30(33,34)35)16-21(15-19)31(36,37)38/h1-9,11,14-16,23-24H,10,12-13,17H2,(H,40,42)/t23-,24+/m0/s1
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| Chemical Name |
N-[(2R,4S)-1-[3,5-bis(trifluoromethyl)benzoyl]-2-[(4-chlorophenyl)methyl]piperidin-4-yl]quinoline-4-carboxamide
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| Synonyms |
NKP608; NKP 608; NKP-608
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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 : ~100 mg/mL (~161.30 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.03 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 (4.03 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 | 1.6129 mL | 8.0646 mL | 16.1293 mL | |
| 5 mM | 0.3226 mL | 1.6129 mL | 3.2259 mL | |
| 10 mM | 0.1613 mL | 0.8065 mL | 1.6129 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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