product name Naftopidil DiHCl
Description: Naftopidil (also known as KT-611) is a selective α1-adrenergic receptor antagonist with Ki of 3.7 nM, 20 nM, and 1.2 nM for α1a, α1b, and α1d, respectively, which is used for the treatment of benign prostatic hyperplasia. Naftopidil is selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines.
References: Jpn J Pharmacol. 1999 Apr;79(4):447-54; Eur J Pharmacol. 2013 Jan 30;700(1-3):194-200.
465.41
Formula
C24H28N2O3.2HCl
CAS No.
57149-08-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 41 mg/mL (88.01mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL (4.23mM)
Solubility (In vivo)
0.5% CMC: 30mg/mL
Synonyms
KT-611
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399027
| In Vitro |
In vitro activity: Naftopidil diHCl possesses 5-HT1A agonistic properties in addition to being an α1-adrenoceptor antagonist. Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. Naftopidil inhibits the growth of androgen-sensitive LNCaP cells and androgen-insensitive PC-3 cells with IC50 of 22.2 μM and 33.2 μM, respectively. Cell growth inhibition by Naftopidil is due to the arrest of the G1 cell cycle. Expressions of p27kip1 and p21cip1 are significantly increased in LNCaP cells treated with Naftopidil. In PC-3 cells, Naftopidil induces p21cip1 but not p27kip1. Naftopidil produces a concentration-dependent inhibition of collagen-induced Ca2+ mobilization, maximum inhibition (22.9%) occurring with 40 μM Naftopidil. The adrenaline-induced rise in [Ca2+]i is inhibited dose dependently by Naftopidil. Naftopidil is significantly more effective than tamsulosin in relieving nocturia. Naftopidil induces G(1) cell-cycle arrest in both PCa cells and PrSC. In Naftopidil-treated PrSC, total interleukin-6 protein is significantly reduced with increased suppression of cell proliferation. Kinase Assay: Cell Assay: Cell cycle analysis is performed by flow cytometry. Cells are treated with either 20 μM Naftopidil (LNCaP), 40 μM Naftopidil (PC-3) or vehicle (0.1% DMSO) for 24 hours, then trypsinized and washed once with phosphate-buffer saline (PBS), fixed in 70% ethanol and stored at 4 °C for subsequent cell cycle analysis. Fixed cells are washed with PBS and incubated with PBS containing 20 μg/mL RNaseA and 0.3% NP-40 for 30 minutes at 37 °C, then stained with 50 μg/mL propidium iodide (PI) for 30 minutes at 4°C in the dark. The DNA content of 1 ?106 stained cells is analyzed on a FACS Caliburflow cytometer. The fractions of cells in the G0/G1, S and G2/M phases are calculated using Cell Quest software. |
|---|---|
| In Vivo | Oral administration of Naftopidil to nude mice inhibits the growth of PC-3 tumors as compared to vehicle-treated controls. Naftopidil improves bladder capacity and relaxed voiding via inhibition of afferent nerve activity. Naftopidil (0.1 μg–30 μg) transiently abolishes isovolumetric rhythmic bladder contraction. The amplitude of bladder contraction is decreased by intrathecal injection of naftopidil (3 μg–30 μg). Naftopidil selectively inhibits the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. |
| Animal model | Athymic nude mice bearing PC-3 cells |
| Formulation & Dosage | Dissolved in 0.5% carboxymethylcellulose; 10 mL/kg/day; p.o. |
| References | Eur J Pharmacol. 1991 Nov 19;205(1):105-7; Int J Cancer. 2008 Jan 15;122(2):444-51. |
Related Posts
product name Naftopidil DiHCl
Description: Naftopidil (also known as KT-611) is a selective α1-adrenergic receptor antagonist with Ki of 3.7 nM, 20 nM, and 1.2 nM for α1a, α1b, and α1d, respectively, which is used for the treatment of benign prostatic hyperplasia. Naftopidil is selective for the alpha1d-adrenoceptor with approximately 3- and 17-fold higher affinity than for the alpha1a- and alpha1b-adrenoceptor subtypes, respectively. Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines.
References: Jpn J Pharmacol. 1999 Apr;79(4):447-54; Eur J Pharmacol. 2013 Jan 30;700(1-3):194-200.
465.41
Formula
C24H28N2O3.2HCl
CAS No.
57149-08-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 41 mg/mL (88.01mM)
Water: <1 mg/mL
Ethanol: 2 mg/mL (4.23mM)
Solubility (In vivo)
0.5% CMC: 30mg/mL
Synonyms
KT-611
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19399027
| In Vitro |
In vitro activity: Naftopidil diHCl possesses 5-HT1A agonistic properties in addition to being an α1-adrenoceptor antagonist. Naftopidil has growth inhibitory effect in androgen-sensitive and -insensitive human prostate cancer cell lines. Naftopidil inhibits the growth of androgen-sensitive LNCaP cells and androgen-insensitive PC-3 cells with IC50 of 22.2 μM and 33.2 μM, respectively. Cell growth inhibition by Naftopidil is due to the arrest of the G1 cell cycle. Expressions of p27kip1 and p21cip1 are significantly increased in LNCaP cells treated with Naftopidil. In PC-3 cells, Naftopidil induces p21cip1 but not p27kip1. Naftopidil produces a concentration-dependent inhibition of collagen-induced Ca2+ mobilization, maximum inhibition (22.9%) occurring with 40 μM Naftopidil. The adrenaline-induced rise in [Ca2+]i is inhibited dose dependently by Naftopidil. Naftopidil is significantly more effective than tamsulosin in relieving nocturia. Naftopidil induces G(1) cell-cycle arrest in both PCa cells and PrSC. In Naftopidil-treated PrSC, total interleukin-6 protein is significantly reduced with increased suppression of cell proliferation. Kinase Assay: Cell Assay: Cell cycle analysis is performed by flow cytometry. Cells are treated with either 20 μM Naftopidil (LNCaP), 40 μM Naftopidil (PC-3) or vehicle (0.1% DMSO) for 24 hours, then trypsinized and washed once with phosphate-buffer saline (PBS), fixed in 70% ethanol and stored at 4 °C for subsequent cell cycle analysis. Fixed cells are washed with PBS and incubated with PBS containing 20 μg/mL RNaseA and 0.3% NP-40 for 30 minutes at 37 °C, then stained with 50 μg/mL propidium iodide (PI) for 30 minutes at 4°C in the dark. The DNA content of 1 ?106 stained cells is analyzed on a FACS Caliburflow cytometer. The fractions of cells in the G0/G1, S and G2/M phases are calculated using Cell Quest software. |
|---|---|
| In Vivo | Oral administration of Naftopidil to nude mice inhibits the growth of PC-3 tumors as compared to vehicle-treated controls. Naftopidil improves bladder capacity and relaxed voiding via inhibition of afferent nerve activity. Naftopidil (0.1 μg–30 μg) transiently abolishes isovolumetric rhythmic bladder contraction. The amplitude of bladder contraction is decreased by intrathecal injection of naftopidil (3 μg–30 μg). Naftopidil selectively inhibits the phenylephrine-induced increase in prostatic pressure compared with mean blood pressure in the anesthetized dog model. |
| Animal model | Athymic nude mice bearing PC-3 cells |
| Formulation & Dosage | Dissolved in 0.5% carboxymethylcellulose; 10 mL/kg/day; p.o. |
| References | Eur J Pharmacol. 1991 Nov 19;205(1):105-7; Int J Cancer. 2008 Jan 15;122(2):444-51. |