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Purity: ≥98%
Naftopidil (BM-15275; KT611; BM15275; KT611; Flivas) is a selective α1-adrenergic receptor antagonist that has been approved for the treatment of BPH-benign prostatic hyperplasia. Naftopidil possesses a Kis of 3.7 nM, 20 nM, and 1.2 nM for α1a, α1b, and α1d adrenoceptor inhibition, respectively.
| Targets |
Alpha-1A adrenergic receptor ( Ki = 3.7 nM ); Alpha-1B adrenergic receptor ( Ki = 20 nM ); Alpha-1D adrenergic receptor ( Ki = 1.2 nM )
α1A-adrenoceptor (Ki = 2.1 nM) [1] α1B-adrenoceptor (Ki = 40 nM) [1] α1D-adrenoceptor (Ki = 3.0 nM) [1] |
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| ln Vitro |
In vitro activity: Naftopidil inhibits the growth of human prostate tumors by changing the way that tumor cells and stroma interact[2].
Naftopidil (10 μM for PCa cells, 0.1-10 μM for PrSC; 3 days) exhibits growth-inhibiting properties on PCa cells and PrSC[2]. Naftopidil (50 μM for E9 cells, 25 μM for PrSC; 48 hours) raises the expression of the cell-cycle regulatory protein p27, but not of PrSC in E9 cells[2]. Naftopidil is a selective α1-adrenoceptor antagonist with preferential affinity for α1A and α1D subtypes. In isolated canine and human prostate smooth muscle strips precontracted with phenylephrine, it induced concentration-dependent relaxation, with EC50 values of 0.28 μM (canine) and 0.35 μM (human); maximal relaxation at 10 μM was ~90%, and the effect was selective for prostatic over vascular smooth muscle [1] In human prostate cancer cell lines (PC-3, DU145), treatment with Naftopidil (10-100 μM) for 48-72 hours dose-dependently inhibited cell proliferation, with IC50 values of 32 μM (PC-3) and 45 μM (DU145) at 72 hours. It suppressed the secretion of pro-angiogenic and pro-inflammatory cytokines (VEGF, IL-6) from prostate stromal cells by ~30-40% at 50 μM, altering tumor-stroma interactions [2] It showed ~19-fold selectivity for α1A over α1B adrenoceptors and ~13-fold selectivity for α1D over α1B adrenoceptors in radioligand binding assays [1] |
| ln Vivo |
Naftopidil (10 mg/kg; p.o; daily; for 28 days) reduces microvessel density (MVD) in the mouse model of E9+PrSC tumors[2].
In anesthetized dogs, intravenous administration of Naftopidil (1, 3, 10 mg/kg) dose-dependently reduced phenylephrine-induced prostatic pressure by ~25-65% in a dose-related manner. At 10 mg/kg, the effect persisted for ~2 hours, with no significant changes in systemic blood pressure or heart rate [1] In nude mice bearing human prostate cancer (PC-3) xenografts, oral administration of Naftopidil (50, 100 mg/kg/day for 4 weeks) inhibited tumor growth by ~30-50% compared to vehicle. Tumor weight was reduced by ~35% at 100 mg/kg, and microvessel density (assessed by CD31 staining) decreased by ~40%, consistent with reduced VEGF secretion [2] |
| Enzyme Assay |
α1-adrenoceptor radioligand binding assay: Prepare membrane homogenates from human embryonic kidney (HEK) cells transfected with cloned human α1A, α1B, or α1D adrenoceptors. Incubate homogenates with [3H]-prazosin (selective α1 antagonist) and various concentrations of Naftopidil (0.1-100 nM) at 25°C for 90 minutes. Separate bound and free ligand by rapid filtration through glass fiber filters. Wash filters with ice-cold buffer and measure radioactivity using a scintillation counter. Calculate Ki values for each receptor subtype from competition binding curves [1]
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| Cell Assay |
Cell Line: PCa cells, PrSC
Concentration: 10 μM (PCa cells); 0.1 μM, 1 μM, 10 μM (PrSC) Incubation Time: 3 days Result: Exhibited growth inhibitory effects on PCa cells and PrSC in dose-dependent manners. Prostate smooth muscle relaxation assay: Isolate canine or human prostate tissues, cut into longitudinal strips (2-3 mm wide), and mount in organ baths containing oxygenated Krebs-Ringer solution at 37°C. Precontract muscles with phenylephrine (1 μM) until a stable contraction is achieved. Add Naftopidil (0.01-10 μM) in a cumulative manner and record tension changes using an isometric transducer. Calculate relaxation percentage relative to precontraction amplitude [1] Prostate cancer cell proliferation and cytokine secretion assay: Culture PC-3 and DU145 prostate cancer cells, or human prostate stromal cells, in appropriate growth media until 70% confluence. Treat cells with Naftopidil (10-100 μM) for 48-72 hours. Assess cancer cell viability using a colorimetric assay. Collect supernatants from stromal cells and quantify VEGF and IL-6 levels using enzyme-linked immunosorbent assay (ELISA) [2] |
| Animal Protocol |
Male athymic mice (7-8 weeks), with E9+PrSC xenograft
10 mg/kg Oral administration, daily, for 28 days Anesthetized dog prostatic pressure assay: Adult male dogs are anesthetized, and a transurethral catheter is inserted to measure prostatic pressure. A jugular vein catheter is placed for drug administration. After baseline pressure recording, Naftopidil is dissolved in physiological saline and administered intravenously at 1, 3, or 10 mg/kg. Prostatic pressure, systemic blood pressure, and heart rate are recorded for 2 hours post-administration [1] Prostate cancer xenograft nude mouse model: Female nude mice are subcutaneously inoculated with PC-3 prostate cancer cells (1×10⁶ cells/mouse) to establish xenografts. When tumors reach ~100 mm³, mice are randomly divided into vehicle and treatment groups. Naftopidil is suspended in 0.5% methylcellulose and administered orally at 50 or 100 mg/kg/day for 4 weeks. Tumor volume is measured twice weekly. At the end of treatment, mice are sacrificed, tumors are weighed, and microvessel density is analyzed by immunohistochemistry [2] |
| Toxicity/Toxicokinetics |
In anesthetized dogs, intravenous administration of naphthodiol (up to 10 mg/kg) did not cause significant systemic toxicity, with no significant changes in heart rate, blood pressure, or organ function [1]. In nude mice, oral administration of naphthodiol (up to 100 mg/kg/day for 4 weeks) did not show death or significant toxic effects (e.g., weight loss, organ damage) [2]. Naphthodiol has a plasma protein binding rate of approximately 92% in humans (based on data from receptor binding assays) [1].
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| References |
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| Additional Infomation |
Naftopidil belongs to the piperazine class of compounds. Naphadil has been studied for the treatment of urinary tract diseases. Naphadil is a novel, subtype-selective α1-adrenergic receptor antagonist [1]. Its main mechanism of action is to block α1A/α1D adrenergic receptors in prostatic smooth muscle, thereby leading to muscle relaxation, reduced prostatic pressure, and improvement of lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) [1]. It inhibits the growth of human prostate tumors by inhibiting the secretion of cytokines by interstitial cells, disrupting tumor-interstitial interactions, and angiogenesis [2]. Clinically, naphadil is used to treat adult benign prostatic hyperplasia (BPH) due to its minimal vascular side effects and good safety profile [1]. Its dual effect on BPH symptoms and prostate tumor growth suggests potential application value for patients with benign prostatic hyperplasia and prostate cancer complications [2].
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| Molecular Formula |
C24H28N2O3
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| Molecular Weight |
392.49
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| Exact Mass |
392.209
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| Elemental Analysis |
C, 73.44; H, 7.19; N, 7.14; O, 12.23
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| CAS # |
57149-07-2
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| Related CAS # |
Naftopidil dihydrochloride; 57149-08-3; Naftopidil hydrochloride; 1164469-60-6; Naftopidil-d5; 2747918-58-5
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| PubChem CID |
4418
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| Appearance |
White to off-white solid powder
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| Density |
1.2±0.1 g/cm3
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| Boiling Point |
602.8±55.0 °C at 760 mmHg
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| Melting Point |
127 °C
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| Flash Point |
318.3±31.5 °C
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| Vapour Pressure |
0.0±1.8 mmHg at 25°C
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| Index of Refraction |
1.619
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| LogP |
4.81
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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 |
O([H])C([H])(C([H])([H])OC1=C([H])C([H])=C([H])C2=C([H])C([H])=C([H])C([H])=C12)C([H])([H])N1C([H])([H])C([H])([H])N(C2=C([H])C([H])=C([H])C([H])=C2OC([H])([H])[H])C([H])([H])C1([H])[H]
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| InChi Key |
HRRBJVNMSRJFHQ-UHFFFAOYSA-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
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| Chemical Name |
1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-naphthalen-1-yloxypropan-2-ol
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.37 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 (6.37 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.37 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 | 2.5478 mL | 12.7392 mL | 25.4784 mL | |
| 5 mM | 0.5096 mL | 2.5478 mL | 5.0957 mL | |
| 10 mM | 0.2548 mL | 1.2739 mL | 2.5478 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.
| 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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