| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Target: alpha1-Adrenergic Receptor (alpha1-AR). Naftopidil is a selective alpha1-adrenoceptor antagonist with Ki values of 3.7 nM (alpha1a), 20 nM (alpha1b), and 1.2 nM (alpha1d) for cloned human receptor subtypes. It has the highest affinity for the alpha1d subtype. The deuterated standard is an analytical tracer with no biological activity.
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| ln Vitro |
Stable heavy isotopes of hydrogen, carbon and other elements have been incorporated into drug molecules, primarily as quantitative tracers during drug development. Deuteration is of concern because of its possible impact on the pharmacokinetics and metabolic characteristics of drugs [1].
In vitro, the labeled standard has no direct activity. The unlabeled Naftopidil (KT-611) is a selective alpha1-adrenoceptor antagonist that inhibits norepinephrine-induced contractions in various isolated blood vessels (e.g., dog aorta, rabbit prostate). It shows functional selectivity for the alpha1d subtype, which is implicated in lower urinary tract symptoms and benign prostatic hyperplasia (BPH). The unlabeled compound also has potential antitumor activity via apoptosis induction in prostate cancer cells. |
| ln Vivo |
In vivo, the unlabeled Naftopidil is used clinically for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). It relaxes smooth muscle in the prostate and bladder neck, improving urine flow. It also shows antihypertensive effects and has been studied for its potential anticancer activity in prostate cancer xenograft models. The deuterated standard is used as an internal standard in PK studies of Naftopidil.
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| Enzyme Assay |
For cell-free assays: plasma, serum, or urine samples are spiked with Naftopidil-d5 internal standard. After protein precipitation with acetonitrile or methanol and centrifugation, the supernatant is injected into an LC-MS/MS system. A C18 reverse-phase column and positive ion mode ESI-MS/MS are typically used. Quantitation of Naftopidil is achieved by comparing the analyte peak area to the internal standard peak area. Isotope dilution mass spectrometry is used to correct for matrix effects and ensure accurate quantitation.
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| Cell Assay |
No cell-based assays are performed with the deuterated standard. The unlabeled Naftopidil is tested in alpha1-AR-expressing cell lines (e.g., HEK293 cells transfected with human alpha1a, alpha1b, or alpha1d receptors) for calcium mobilization assays. Cells are loaded with calcium-sensitive dyes (e.g., Fluo-4), treated with Naftopidil (0.1-1000 nM), and fluorescence is measured to determine antagonism of norepinephrine-induced calcium flux. Ki values are calculated from Schild plots.
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| Animal Protocol |
No animal studies are conducted with the labeled internal standard itself. For PK studies of Naftopidil, animals (rats, dogs) are administered the unlabeled drug orally or intravenously. Serial blood samples are collected, plasma is processed, and the deuterated internal standard is used in LC-MS/MS bioanalysis to determine Naftopidil concentrations. PK parameters (Cmax, Tmax, t1/2, AUC, bioavailability) are calculated. The standard is also used in tissue distribution and metabolism studies.
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| ADME/Pharmacokinetics |
PK properties of Naftopidil: after oral administration (20-50 mg in humans), it is rapidly absorbed with Tmax 0.5-2 h. Oral bioavailability is approximately 30-50% due to first-pass metabolism. Plasma protein binding is high (>90%). It is extensively metabolized by CYP450 enzymes (primarily CYP3A4) to several metabolites. The terminal elimination half-life is approximately 5-10 h. Excretion occurs mainly via urine and feces. The deuterated standard co-elutes with the analyte, ensuring accurate PK parameter determination by stable isotope dilution LC-MS/MS.
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| Toxicity/Toxicokinetics |
No toxicity data are reported for the deuterated standard. The unlabeled Naftopidil has a well-characterized safety profile: common adverse effects include dizziness, hypotension, nasal congestion, asthenia, and headache. It may cause orthostatic hypotension, especially in elderly patients. Unlike some alpha1-blockers, it has a lower incidence of ejaculatory dysfunction. The labeled compound is for research use only and not intended for human therapeutic administration.
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| References |
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| Additional Infomation |
Naftopidil-d5 is a research standard and not an active drug substance. The unlabeled Naftopidil (Flivas, Avishot) is approved in Japan, China, and other Asian countries for the treatment of benign prostatic hyperplasia (BPH) and lower urinary tract symptoms (LUTS). It is also being investigated for the treatment of prostate cancer in clinical trials. The deuterated standard is used for analytical method development, method validation (AMV), quality control (QC), and abbreviated new drug application (ANDA) submissions for Naftopidil-containing pharmaceutical products.
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| Molecular Formula |
C24H28N2O3
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|---|---|
| Molecular Weight |
397.521534919739
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| Exact Mass |
397.241
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| CAS # |
2747918-58-5
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| Related CAS # |
Naftopidil;57149-07-2
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| PubChem CID |
131709095
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
4.1
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
29
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| Complexity |
483
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| Defined Atom Stereocenter Count |
0
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| SMILES |
OC([2H])(C([2H])([2H])OC1=CC=CC2C=CC=CC1=2)C([2H])([2H])N1CCN(C2C=CC=CC=2OC)CC1
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| InChi Key |
HRRBJVNMSRJFHQ-XOYZCUSZSA-N
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| InChi Code |
InChI=1S/C24H28N2O3/c1-28-24-11-5-4-10-22(24)26-15-13-25(14-16-26)17-20(27)18-29-23-12-6-8-19-7-2-3-9-21(19)23/h2-12,20,27H,13-18H2,1H3/i17D2,18D2,20D
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| Chemical Name |
1,1,2,3,3-pentadeuterio-1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-naphthalen-1-yloxypropan-2-ol
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5156 mL | 12.5780 mL | 25.1560 mL | |
| 5 mM | 0.5031 mL | 2.5156 mL | 5.0312 mL | |
| 10 mM | 0.2516 mL | 1.2578 mL | 2.5156 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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