| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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Purity: ≥98%
| Targets |
The primary target of NSC23925 HCl is P-glycoprotein (P-gp), an ATP-dependent efflux transporter that pumps a wide variety of drugs out of cells. Overexpression of P-gp is a major mechanism of multidrug resistance in cancer cells. By inhibiting P-gp, NSC23925 prevents the efflux of chemotherapeutic agents, thereby increasing their intracellular concentration and restoring their cytotoxic effects. It selectively reverses P-gp-mediated resistance over MRP1/ABCC1 and BCRP/ABCG2-mediated resistance.
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| ln Vitro |
An innovative, efficient, and selective P-glycoprotein (Pgp) inhibitor is NSC23925. After being exposed to 1 μM NSC23925 for an extended period of time, SKOV-3 cells exhibit consistent proliferation in the culture medium. In order to stop paclitaxel resistance from developing while the drug is being administered, NSC23925 directly suppresses the overexpression of Pgp[1]. In several different tumor types where Multidrug resistance 1 (MDR1) is highly expressed, NSC23925 restores chemoresistance. NSC23925 dosages between 0.5 and 1 µM usually result in the maximum reversal of MDR. While the mean concentration of NSC23925 needed for the greatest reversal of resistance in SKOV-3TR or OVCAR8TR to cytotoxic medicines is 0.5 µM to 1 µM, the IC50 for NSC23925 is 8 µM in SKOV-3/SKOV-3TR and 25 µM in OVCAR8/OVCAR8TR cell lines[2].
NSC23925 HCl is a potent inhibitor of P-glycoprotein (P-gp). It selectively reverses multidrug resistance mediated by P-gp. The compound does not inhibit MRP1 or BCRP, indicating its selectivity for P-gp. In vitro activity is typically assessed using cell lines that overexpress P-gp and are resistant to chemotherapeutic drugs such as paclitaxel or doxorubicin. NSC23925 enhances the cytotoxicity of these drugs in resistant cells by blocking their efflux. |
| ln Vivo |
Tumors treated with NSC23925 alone or saline alone both develop more slowly over time. The anticancer activity of paclitaxel is considerably prolonged when NSC23925 is used in combination with chemotherapy[1].
In vivo activity data for NSC23925 HCl are not detailed in the available sources. As a P-gp inhibitor, its potential application is in combination with chemotherapeutic agents to overcome multidrug resistance in cancer patients. The compound is expected to enhance the antitumor efficacy of P-gp substrate drugs in vivo, but specific animal model studies are not described in the available summaries. |
| Enzyme Assay |
A P-gp inhibition assay typically uses membrane vesicles prepared from cells overexpressing human P-gp. The assay measures the ATP-dependent uptake of a fluorescent substrate (e.g., rhodamine 123 or calcein-AM) into the vesicles. NSC23925 is added at various concentrations, and the inhibition of substrate uptake is measured. The IC50 for inhibition of P-gp-mediated transport is calculated. Alternatively, a cell-based efflux assay can be performed using P-gp-overexpressing cells loaded with a fluorescent substrate. Specific protocols are not detailed in the available sources.
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| Cell Assay |
To determine whether NSC23925 2HCl (NSC23925 dihyrochloride) can prevent the emergence of paclitaxel resistance, paclitaxel resistant ovarian cancer cells are used. In brief, 1×105 SKOV-3 cells are suspended in culture media containing paclitaxel alone, 1 μM NSC23925 alone, or paclitaxel in combination with 1 μM NSC23925. When the cells are cultured to 90% confluence, 1×105 cells are reseeded in a new tissue culture flask, and the paclitaxel dose is increased stepwise. The initial concentration of paclitaxel is 0.0001 μM. At different selection points cell sublines are collected and stored at liquid nitrogen for further analysis[1].
To evaluate the ability of NSC23925 to reverse multidrug resistance, P-gp-overexpressing cancer cells (e.g., KB-V1 or MCF-7/ADR) are plated in 96-well plates. Cells are treated with varying concentrations of a chemotherapeutic drug (e.g., paclitaxel or doxorubicin) alone or in combination with a fixed concentration of NSC23925. After 72 hours of incubation, cell viability is measured using an MTT or SRB assay. The reversal of resistance is expressed as the fold-increase in drug sensitivity (i.e., the ratio of IC50 of the drug alone to IC50 of the drug in combination with NSC23925). |
| Animal Protocol |
Specific in vivo animal experiment protocols for NSC23925 HCl are not detailed in the available sources. The compound has not been described in the context of xenograft models or other in vivo efficacy studies. Given its in vitro activity as a P-gp inhibitor, it may be evaluated in combination with chemotherapeutic agents in xenograft models of drug-resistant tumors, but such data are not currently available.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for NSC23925 HCl are not provided in the available sources. The compound is a small molecule with a molecular weight of 421.4 and is soluble in water at 5 mg/mL. It is a P-gp inhibitor, and its own pharmacokinetic properties would be important for its potential use as an adjuvant therapy. Standard pharmacokinetic studies would typically involve administering the compound to rodents and measuring plasma concentrations over time using LC-MS/MS.
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| Toxicity/Toxicokinetics |
Specific toxicity data for NSC23925 HCl are not provided in the available sources. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. The compound is typically stored at -20°C for long-term stability. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
NSC23925 HCl is a novel, potent, selective, and effective P-glycoprotein (P-gp) inhibitor that is able to reverse multidrug resistance (MDR). It selectively reverses P-gp-mediated multidrug resistance over MRP1- or BCRP-mediated resistance. The compound has a molecular weight of 421.36 and a CAS number of 858474-14-3. It is supplied for research purposes with a purity of >98%.
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| Molecular Formula |
C22H26CL2N2O2
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|---|---|
| Molecular Weight |
421.360044002533
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| Exact Mass |
420.137
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| CAS # |
858474-14-3
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| PubChem CID |
91885392
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.216
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
28
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| Complexity |
438
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
WGWOQHWZXLGPNG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24N2O2.2ClH/c1-26-16-11-9-15(10-12-16)21-14-18(17-6-2-3-7-19(17)24-21)22(25)20-8-4-5-13-23-20;;/h2-3,6-7,9-12,14,20,22-23,25H,4-5,8,13H2,1H3;2*1H
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| Chemical Name |
2-(p-Methoxyphenyl)-α-2-piperidyl-4-quinolinemethanol Dihydrochloride
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| Synonyms |
NSC 23925; NSC23925 dihyrochloride; NSC-23925; NSC 23925 diHCl
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 : ~14.29 mg/mL (~33.91 mM)
H2O : ~4 mg/mL (~9.49 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.43 mg/mL (3.39 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 14.3 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: ≥ 1.43 mg/mL (3.39 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 14.3 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 | 2.3733 mL | 11.8663 mL | 23.7327 mL | |
| 5 mM | 0.4747 mL | 2.3733 mL | 4.7465 mL | |
| 10 mM | 0.2373 mL | 1.1866 mL | 2.3733 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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