| Size | Price | Stock | Qty |
|---|---|---|---|
| 100mg |
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| Other Sizes |
| Targets |
Alpha-1A adrenergic receptor 3.7 nM (Ki) Alpha-1B adrenergic receptor 20 nM (Ki) Alpha-1D adrenergic receptor 1.2 nM (Ki)
Naftopidil hydrochloride targets the α1-adrenoceptor, specifically showing high affinity for the α1d subtype (Ki = 1.2 nM), moderate affinity for α1a (Ki = 3.7 nM), and lower affinity for α1b (Ki = 20 nM). It has only weak antagonism at post-junctional α2 receptors. By blocking these receptors, it inhibits smooth muscle contraction in the prostate and bladder neck, improving urinary flow and reducing lower urinary tract symptoms. |
|---|---|
| ln Vitro |
By changing the connections between tumor cells and stroma, naftopidil hydrochloride inhibits the growth of human prostate tumors[2]. Growth inhibitory effects are observed on PCa cells and PrSC when treated with naftopidil hydrochloride (10 μM for PCa cells, 0.1-10 μM for PrSC; 3 days)[2]. In E9 cells, but not in PrSC, naptopidil hydrochloride (50 μM for E9 cells, 25 μM for PrSC; 48 hours) raises the amount of the cell-cycle regulating protein p27[2].
In vitro, Naftopidil hydrochloride demonstrates antiproliferative activity, inhibiting the growth of androgen-sensitive LNCaP cells and androgen-insensitive PC-3 cancer cell lines with IC50 values of 22.2 and 33.2 µM, respectively. It shows selective inhibition of cloned human α1-adrenoceptor subtypes with distinct binding affinities. In mouse models, the compound reduces pulmonary fibrosis and SP-D production in a bleomycin-induced lung fibrosis model. |
| ln Vivo |
In a mouse model with E9+PrSC tumors, naptopidil hydrochloride (10 mg/kg; po; daily; for 28 days) reduces microvessel density (MVD)[2].
In vivo, Naftopidil hydrochloride significantly inhibits the proliferation of stromal cells, leading to a reduction in tumor-promoting soluble factors, suggesting it may effectively block stromal support of tumor cells. It acts as a potent, persistent antihypertensive and vasodilator. Clinical formulations of naftopidil are used in the treatment of benign prostatic hyperplasia in Japan. The compound has demonstrated efficacy in relieving lower urinary tract symptoms compatible with BPH. |
| Enzyme Assay |
For non-cell-based receptor binding assays, Naftopidil hydrochloride can be evaluated using membrane preparations from cells expressing cloned human α1-adrenoceptor subtypes. Radioligand binding displacement experiments are performed using a suitable radiolabeled ligand such as [3H]-prazosin. Membrane homogenates are incubated with increasing concentrations of the test compound and a fixed concentration of the radioligand at room temperature for 60-120 minutes. Bound radioligand is separated from free by rapid filtration through glass fiber filters. Nonspecific binding is determined in the presence of excess unlabeled prazosin. Ki values are calculated from displacement curves using nonlinear regression analysis.
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: PCa cells , PrSC Tested Concentrations: 10 μM (PCa cells); 0.1 μM, 1 μM, 10 μM (PrSC) Incubation Duration: 3 days Experimental Results: demonstrated growth inhibitory effects on PCa cells and PrSC in dose-dependent manners. Western Blot Analysis[2] Cell Types: PCa cells, PrSC Tested Concentrations: 50 μM (E9 cells), 25 μM (PrSC) Incubation Duration: 48 hrs (hours) Experimental Results: Increased the level of cell-cycle regulatory protein p27 in E9 cells, but not PrSC. For in vitro cellular assays, cells expressing human α1a, α1b, or α1d adrenoceptor subtypes are cultured in appropriate media. For functional assays, intracellular calcium mobilization is measured using fluorescent calcium indicators such as Fluo-4 AM. Cells are loaded with the dye and pre-incubated with various concentrations of Naftopidil hydrochloride. Receptor activation is stimulated by the addition of an α1-adrenoceptor agonist such as phenylephrine. Fluorescence intensity is measured using a fluorescence plate reader. The reduction in calcium signal compared to control wells indicates antagonist activity. IC50 values are calculated from dose-response curves. |
| Animal Protocol |
Animal/Disease Models: Male athymic mice(7-8 weeks), with E9+PrSC xenograft[2]
Doses: 10 mg/kg Route of Administration: Oral administration, daily, for 28 days Experimental Results: diminished tumor weights. For in vivo animal studies, Naftopidil hydrochloride is typically administered to rodents via oral gavage or intraperitoneal injection. In models of benign prostatic hyperplasia, prostate weight and volume are measured following compound administration. In hypertension models, blood pressure is monitored via tail-cuff or telemetry. In the bleomycin-induced pulmonary fibrosis model in mice, lung fibrosis severity and SP-D production are assessed. In cancer models, tumor growth and stromal cell proliferation are evaluated. Dosing regimens vary depending on the specific model and desired exposure levels. Blood and tissue samples are collected for pharmacokinetic analysis. |
| ADME/Pharmacokinetics |
Naftopidil hydrochloride has a molecular weight of 428.96 and is soluble in DMSO up to 100 mM. It is a white crystalline solid with a purity of ≥98% by HPLC. The compound is typically stored in a cool, dry place. As an oral alpha-blocking agent, it demonstrates good oral bioavailability and is used clinically in Japan for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. The compound's pharmacokinetic profile supports once-daily dosing in clinical use.
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| Toxicity/Toxicokinetics |
The toxicity profile of Naftopidil hydrochloride has been established through clinical use for benign prostatic hyperplasia. Common adverse effects may include dizziness, hypotension, and asthenia due to its vasodilatory properties. The compound's safety profile is generally favorable, with adverse effects typically manageable. As an α1-adrenoceptor antagonist, it may cause orthostatic hypotension, particularly at the initiation of therapy. The compound is for research use only and not for human consumption outside approved clinical indications. Standard toxicological evaluation would include acute and repeated-dose toxicity studies.
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| References |
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| Additional Infomation |
Naftopidil hydrochloride (KT-611 hydrochloride; BM-15275 hydrochloride) is a selective α1-adrenoceptor antagonist with Ki values of 3.7 nM, 20 nM, and 1.2 nM for α1a, α1b, and α1d subtypes, respectively. It is used clinically for the treatment of benign prostatic hyperplasia in Japan. The compound also exhibits antiproliferative activity against cancer cell lines. Naftopidil has been evaluated in Cochrane systematic reviews for the treatment of lower urinary tract symptoms compatible with BPH. Its mechanism involves selective α1d blockade, which is central to prostatic smooth-muscle contraction.
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| Molecular Formula |
C24H29CLN2O3
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|---|---|
| Exact Mass |
428.186
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| CAS # |
1164469-60-6
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| Related CAS # |
Naftopidil;57149-07-2;Naftopidil dihydrochloride;57149-08-3
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| PubChem CID |
6603044
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
30
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| Complexity |
483
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| Defined Atom Stereocenter Count |
0
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| SMILES |
COC1=CC=CC=C1N2CCN(CC2)CC(COC3=CC=CC4=CC=CC=C43)O.Cl
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| InChi Key |
VQAAEWMEVIOHTJ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H28N2O3.ClH/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;1H
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| Chemical Name |
1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-naphthalen-1-yloxypropan-2-ol;hydrochloride
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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.) |
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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00967772 | Completed | Drug: Naftopidil | Healthy | Dong-A ST Co., Ltd. | September 2009 | Phase 1 |
| NCT01959074 | Completed | Drug: Naftopidil Drug: Placebo for Naftopidil |
Disorder of Urinary Stent | Seoul National University Hospital | May 2014 | Phase 3 |
| NCT01952314 | Completed | Drug: Naftopidil 75mg Drug: Placebo for Naftopidil |
Ureter Stones | Seoul National University Hospital |
May 2014 | Phase 3 |
| NCT01922375 | Completed | Drug: Naftopidil | Lower Urinary Tract Symptoms Associated With Benign Prostatic Hyperplasia |
Dong-A Pharmaceutical Co., Ltd. |
December 2011 | Phase 4 |
| NCT02034604 | Completed | Drug: Naftofidil Drug: Tamsulosin |
Neurogenic Lower Urinary Tract Dysfunction |
Samsung Medical Center | December 2013 | Phase 4 |
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