Dutasteride

Names

[ Name ]:
Dutasteride

[Synonym ]:
(5a,17b)-N-(2,5-Bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide
(5α,17β)-N-(2,5-Bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide
Avodart
Duagen
α,α,α,α',α',α'-Hexafluoro-3-oxo-4-aza-5α-androst-1-ene-17β-carboxy-2',5'-xylidide
Dutasteride
(4aR,4bS,6aS,7S,9aS,9bS,11aR)-N-[2,5-Bis(trifluoromethyl)phenyl]-4a,6a-dimethyl-2-oxo-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-1H-indeno[5,4-f]quinoline-7-carboxamide
1H-Indeno[5,4-f]quinoline-7-carboxamide, N-[2,5-bis(trifluoromethyl)phenyl]-2,4a,4b,5,6,6a,7,8,9,9a,9b,10,11,11a-tetradecahydro-4a,6a-dimethyl-2-oxo-, (4aR,4bS,6aS,7S,9aS,9bS,11aR)-
a,a,a,a',a',a'-Hexafluoro-3-oxo-4-aza-5a-androst-1-ene-17b-carboxy-2',5'-xylidide

Biological Activity

[Description]:

Dutasteride (GG745) is a potent inhibitor of both 5 alpha-reductase isozymes. Dutasteride may possess off-target effects on the androgen receptor (AR) due to its structural similarity to DHT.IC50 Value:Target: 5 alpha-reductasein vitro: Dutasteride inhibited (3)H-T conversion to (3)H-DHT and, as anticipated, inhibited T-induced secretion of PSA and proliferation. However the drug also inhibited DHT-induced PSA secretion and cell proliferation (IC(50) approximately 1 microM). Dutasteride competed for binding the LNCaP cell AR with an IC(50) approximately 1.5 microM. High concentrations of dutasteride (10-50 microM), but not finasteride, in steroid-free medium, resulted in enhanced cell death, possibly by apoptosis [1]. Dutasteride reduces cell viability and cell proliferation in both cell lines tested (androgen-responsive (LNCaP) and androgen-unresponsive (DU145) human prostate cancer (PCa)) [2].in vivo: GG745 has a terminal half-life of approximately 240 hr, and single doses of >10 mg decreased DHT levels significantly more than did single 5-mg doses of finasteride [3]. In placebo treated men without prostate cancer there was an 8.3% median increase in PSA at month 24 compared with -59.5% in those who received dutasteride, using doubled values to correct for dutasteride treatment [4].Toxicity: Dutasteride may affect male fertility and steroid hormone dynamics. Therefore, a 21-day reproduction study was conducted to determine the effects of dutasteride (10, 32 and 100 μg/L) on fish reproduction. Exposure to dutasteride significantly reduced fecundity of fish and affected several aspects of reproductive endocrine functions in both males and females [5].Clinical trial: Bioequivalence Study Of Dutasteride Five 0.1 mg And One 0.5 mg Soft Gelatin Capsules In Healthy Male Volunteers. Phase 1

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> 5 alpha Reductase

Research Areas >> Cancer

[References]

[1]. Lazier CB, et al. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004 Feb 1;58(2):130-44.

[2]. Biancolella M, et al. Effects of dutasteride on the expression of genes related to androgen metabolism and related pathway in human prostate cancer cell lines. Invest New Drugs. 2007 Oct;25(5):491-7.

[3]. Bramson HN, et al. Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR. J Pharmacol Exp Ther. 1997 Sep;282(3):1496-502.

[4]. Andriole GL, et al. Clinical usefulness of serum prostate specific antigen for the detection of prostate cancer is preserved in men receiving the dual 5alpha-reductase inhibitor dutasteride. J Urol. 2006 May;175(5):1657-62.

[5]. Margiotta-Casaluci L, et al. Mode of action of human pharmaceuticals in fish: the effects of the 5-alpha-reductase inhibitor, dutasteride, on reproduction as a case study. Aquat Toxicol. 2013 Mar 15;128-129:113-23.

[Related Small Molecules]

Finasteride | Epristeride | CGP-53153

Chemical & Physical Properties

[ Density]:
1.3±0.1 g/cm3

[ Boiling Point ]:
620.3±55.0 °C at 760 mmHg

[ Melting Point ]:
242-250ºC

[ Molecular Formula ]:
C₂₇H₃₀F₆N₂O₂

[ Molecular Weight ]:
528.530

[ Flash Point ]:
329.0±31.5 °C

[ Exact Mass ]:
528.221130

[ PSA ]:
58.20000

[ LogP ]:
5.61

[ Vapour Pressure ]:
0.0±1.8 mmHg at 25°C

[ Index of Refraction ]:
1.523

[ Storage condition ]:
-20°C Freezer

[ Water Solubility ]:
DMSO: soluble2mg/mL, clear

Safety Information

[ RIDADR ]:
NONH for all modes of transport

[ HS Code ]:
2942000000

Customs

[ HS Code ]: 2933990090

[ Summary ]:
2933990090. heterocyclic compounds with nitrogen hetero-atom(s) only. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:20.0%

Articles

Next-generation steroidogenesis inhibitors, dutasteride and abiraterone, attenuate but still do not eliminate androgen biosynthesis in 22RV1 cells in vitro

J. Steroid Biochem. Mol. Biol. 144 Pt B , 436-44, (2014)

• Dutasteride and abiraterone were evaluated for inhibition of steroidogenesis. • Bypass mechanisms arise in the presence of abiraterone to form DHT. • Dutasteride inhibits T and DHT effectively in vi...

Preparation of microcapsules with the evaluation of physicochemical properties and molecular interaction.

Arch. Pharm. Res. 37(12) , 1570-7, (2014)

The objective of this study was to prepare and characterize dutasteride (a hydrophobic model drug) microcapsules using ethyl cellulose as a capsule shell polymer with different drug/polymer ratios of ...

Long term effectiveness on prescribing of two multifaceted educational interventions: results of two large scale randomized cluster trials.

PLoS ONE 9(10) , e109915, (2014)

Information on benefits and risks of drugs is a key element affecting doctors' prescribing decisions. Outreach visits promoting independent information have proved moderately effective in changing pre...