Naftopidil 2HCl 57149-08-3_Adrenergic Receptor_GPCR & G Protein_Signaling Pathways_Products

Naftopidil 2HCl (BM-15275; KT-611; BM15275; KT611; Flivas), the dihydrochloride salt of Naftopidil, is a potent and selective α1-adrenergic receptor antagonist with antihypertensive effects. It has a Kis of 3.7 nM, 20 nM, and 1.2 nM for α1a, α1b, and α1d adrenergic receptor inhibition, respectively. Benign prostatic hyperplasia, or BPH, may now be treated with naftopidil. When compared to the alpha1a- and alpha1b-adrenoceptor subtypes, naptopidil has a selectivity for the alpha1d-adrenoceptor that is roughly 3- and 17-fold higher, respectively. In human prostate cancer cell lines that are both androgen-sensitive and -insensitive, naftopidil inhibits the growth of the cells.

Physicochemical Properties

Molecular Formula

C24H30CL2N2O3

Molecular Weight

465.41

Exact Mass

392.209

Elemental Analysis

C, 61.94; H, 6.50; Cl, 15.23; N, 6.02; O, 10.31

CAS #

57149-08-3

Related CAS #

Naftopidil; 57149-07-2; Naftopidil hydrochloride; 1164469-60-6

PubChem CID

11957660

Appearance

Solid powder

Density

1.2±0.1 g/cm3

Boiling Point

602.8±55.0 °C at 760 mmHg

Melting Point

212-213°

Flash Point

318.3±31.5 °C

Vapour Pressure

0.0±1.8 mmHg at 25°C

Index of Refraction

1.619

LogP

4.81

Hydrogen Bond Donor Count

Hydrogen Bond Acceptor Count

Rotatable Bond Count

Heavy Atom Count

Complexity

483

Defined Atom Stereocenter Count

SMILES

Cl[H].Cl[H].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]

InChi Key

HZVCEQMJXMUXJF-UHFFFAOYSA-N

InChi Code

InChI=1S/C24H28N2O3.2ClH/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;2*1H

Chemical Name

1-[4-(2-methoxyphenyl)piperazin-1-yl]-3-naphthalen-1-yloxypropan-2-ol;dihydrochloride

Synonyms

KT-611; BM-15275; KT611; BM 15275; KT 611; BM15275; KT611; Flivas

HS Tariff Code

2934.99.9001

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)

Biological Activity

Targets

Alpha-1A adrenergic receptor ( Ki = 3.7 nM ); Alpha-1B adrenergic receptor ( Ki = 20 nM ); Alpha-1D adrenergic receptor ( Ki = 1.2 )

ln Vitro

In vitro activity: Naftopidil diHCl is an α1-adrenoceptor antagonist and also has 5-HT1A agonistic qualities.[1] In both androgen-sensitive and -insensitive human prostate cancer cell lines, naftopidil inhibits cell growth. With an IC50 of 22.2 μM and 33.2 μM, respectively, naftopidil suppresses the growth of androgen-sensitive LNCaP cells and androgen-insensitive PC-3 cells. The G1 cell cycle is stopped by naptopidil, which inhibits cell growth. In LNCaP cells treated with Naftopidil, there is a significant increase in the expression of p27^kip1 and p21^cip1. Naftopidil induces p21^cip1 but not p27^kip1 in PC-3 cells.[2] Naftopidil inhibits collagen-induced Ca²⁺ mobilization in a concentration-dependent manner; 40 μM Naftopidil produces the greatest inhibition (22.9%). Naftopidil reduces [Ca²⁺]i in a dose-dependent manner, counteracting the effects of adrenaline. In terms of relieving nocturia, naftopidil works much better than tamsulosin. In PCa cells as well as PrSC, naftopidil causes G(1) cell-cycle arrest[4]. Interleukin-6 protein total is markedly decreased in PrSC treated with naptopidil, and cell proliferation is more strongly suppressed.[5]

ln Vivo

Comparing oral Naftopidil administration to vehicle-treated controls, the development of PC-3 tumors is inhibited in nude mice. Through the suppression of afferent nerve activity, naptopidil increases bladder capacity and promotes relaxed voiding.[2] Naftopidil (0.1 μg–30 μg) temporarily eliminates bladder contraction that is isovolumetric in rhythm. Intrathecal injection of naftopidil (3 μg–30 μg) reduces the amplitude of bladder contraction.[6] In the anesthetized dog model, naptopidil specifically prevents the rise in prostatic pressure brought on by phenylephrine when compared to mean blood pressure.[7]

Cell Assay

Flow cytometry is used to analyze cell cycles. After treating the cells for 24 hours with either 20 μM Naftopidil (LNCaP), 40 μM Naftopidil (PC-3), or vehicle (0.1% DMSO), the cells are trypsinized, once again cleaned with phosphate-buffer saline (PBS), fixed in 70% ethanol, and kept at 4 °C for the purpose of cell cycle analysis. After fixed cells are rinsed with PBS, they are incubated for 30 minutes at 37 °C in PBS containing 20 μg/mL RNaseA and 0.3% NP-40. Afterwards, they are stained for 30 minutes at 4 홈 in the dark with 50 μg/mL propidium iodide (PI). One FACS Caliburflow cytometer is used to analyze the DNA content of one million stained cells. Using Cell Quest software, the fractions of cells in the G0/G1, S, and G2/M phases are computed.

Animal Protocol

Dissolved in 0.5% carboxymethylcellulose; 10 mL/kg/day; p.o.

Athymic nude mice bearing PC-3 cells

References

[1]. Eur J Pharmacol . 1991 Nov 19;205(1):105-7.

[2]. Int J Cancer . 2008 Jan 15;122(2):444-51.

[3]. Br J Clin Pharmacol . 1997 Apr;43(4):415-20.

[1]. BJU Int . 2006 Apr;97(4):747-51, discussion 751.

[2]. Cancer Prev Res (Phila) . 2011 Jan;4(1):87-96.

[3]. Neurosci Lett . 2002 Aug 2;328(1):74-6.

[3]. Jpn J Pharmacol . 1999 Apr;79(4):447-54.

Solubility Data

Solubility (In Vitro)

DMSO: ~41 mg/mL (~88.0 mM)

Water: <1 mg/mL

Ethanol: ~2 mg/mL (~4.2 mM)

Solubility (In Vivo)

0.5% CMC: 30mg/mL

(Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.1486 mL	10.7432 mL	21.4864 mL
	5 mM	0.4297 mL	2.1486 mL	4.2973 mL
	10 mM	0.2149 mL	1.0743 mL	2.1486 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.

PeptideDB

Naftopidil 2HCl 57149-08-3

CAS No.: 57149-08-3

Physicochemical Properties

Biological Activity

Solubility Data