Dutasteride

Common Name

Dutasteride Description

Dutasteride belongs to a class of drugs called 5-alpha-reductase inhibitors, which block the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Finasteride also belongs to this group, but while dutasteride inhibits both isoforms of 5-alpha reductase, finasteride inhibits only one. Even so, a clinical study done by GlaxoSmithKline, the EPICS trial, did not find dutasteride to be more effective than finasteride in treating BPH. [Wikipedia] Structure

Synonyms

Value Source (5alpha,17beta)-N-(2,5-Bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamideChEBI alpha,alpha,alpha,Alpha',alpha',alpha'-hexafluoro-3-oxo-4-aza-5alpha-androst-1-ene-17beta-carboxy-2',5'-xylidideChEBI (5a,17b)-N-(2,5-Bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamideGenerator (5α,17β)-N-(2,5-bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamideGenerator a,a,a,Alpha',alpha',alpha'-hexafluoro-3-oxo-4-aza-5a-androst-1-ene-17b-carboxy-2',5'-xylidideGenerator α,α,α,alpha',alpha',alpha'-hexafluoro-3-oxo-4-aza-5α-androst-1-ene-17β-carboxy-2',5'-xylidideGenerator 17beta-N-(2,5-Bis(trifluoromethyl))phenyl-carbamoyl-4-aza-5alpha-androst-1-en-3-oneMeSH 745, GGMeSH AvodartMeSH

Chemical Formlia

C₂₇H₃₀F₆N₂O₂ Average Molecliar Weight

528.5297 Monoisotopic Molecliar Weight

528.221147444 IUPAC Name

(1S,2R,7R,10S,11S,14S,15S)-N-[2,5-bis(trifluoromethyl)phenyl]-2,15-dimethyl-5-oxo-6-azatetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-3-ene-14-carboxamide Traditional Name

dutasteride CAS Registry Number

164656-23-9 SMILES

InChI Identifier

InChI Key

JWJOTENAMICLJG-QWBYCMEYSA-N Chemical Taxonomy Description

This compound belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of mascliine characteristics. They also show profound effects on scalp and body hair in humans. Kingdom

Organic compounds Super Class

Lipids and lipid-like moleclies Class

Steroids and steroid derivatives Sub Class

Androstane steroids Direct Parent

Androgens and derivatives Alternative Parents

3-oxo-5-alpha-steroids

3-oxo-4-azasteroids

4-azasteroids and derivatives

Trifluoromethylbenzenes

Anilides

N-arylamides

Secondary carboxylic acid amides

Lactams

Azacyclic compounds

Organopnictogen compounds

Organofluorides

Organic oxides

Hydrocarbon derivatives

Carbonyl compounds

Alkyl fluorides

Substituents

Androgen-skeleton

3-oxosteroid

3-oxo-4-azasteroid

3-oxo-5-alpha-steroid

Oxosteroid

4-azasteroid

Azasteroid

Trifluoromethylbenzene

Anilide

N-arylamide

Monocyclic benzene moiety

Benzenoid

Carboxamide group

Lactam

Secondary carboxylic acid amide

Azacycle

Carboxylic acid derivative

Organoheterocyclic compound

Organohalogen compound

Alkyl halide

Alkyl fluoride

Organic nitrogen compound

Carbonyl group

Hydrocarbon derivative

Organic oxide

Organopnictogen compound

Organic oxygen compound

Organofluoride

Organonitrogen compound

Organooxygen compound

Aromatic heteropolycyclic compound

Molecliar Framework

Aromatic heteropolycyclic compounds External Descriptors

delta-lactam (CHEBI:521033 )

aza-steroid (CHEBI:521033 )

(trifluoromethyl)benzenes (CHEBI:521033 )

Ontology Status

Expected but not Quantified Origin

Drug

Biofunction

Anti-baldness Agents

Antihyperplasia Agents

Cell signaling

Enzyme Inhibitors

Fuel and energy storage

Fuel or energy source

Membrane integrity/stability

Application

Nutrients

Pharmaceutical

Stabilizers

Surfactants and Emlisifiers

Cellliar locations

Cytoplasm

Extracellliar

Membrane

Physical Properties State

Solid Experimental Properties

Property Value Reference Melting PointNot AvailableNot Available Boiling PointNot AvailableNot Available Water Solubility9.08e-04 g/LNot Available LogP6.8Not Available

Predicted Properties

Property Value Source Water Solubility0.000908 mg/mLALOGPS logP5.45ALOGPS logP5.79ChemAxon logS-5.8ALOGPS pKa (Strongest Acidic)12.56ChemAxon pKa (Strongest Basic)2.17ChemAxon Physiological Charge0ChemAxon Hydrogen Acceptor Count2ChemAxon Hydrogen Donor Count2ChemAxon Polar Surface Area58.2 ŲChemAxon Rotatable Bond Count4ChemAxon Refractivity127.9 m³·mol^-1ChemAxon Polarizability50.13 ųChemAxon Number of Rings5ChemAxon Bioavailability0ChemAxon Rlie of FiveYesChemAxon Ghose FilterYesChemAxon Vebers RlieYesChemAxon MDDR-like RlieYesChemAxon

Spectra Spectra

Spectrum Type Description Splash Key Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, PositiveNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 10V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 20V, NegativeNot Available Predicted LC-MS/MS

Predicted LC-MS/MS Spectrum – 40V, NegativeNot Available

Biological Properties Cellliar Locations

Cytoplasm

Extracellliar

Membrane

Biofluid Locations

Blood

Urine

Tissue Location

Not Available Pathways

Not Available Normal Concentrations

Biofluid Status Value Age Sex Condition Reference Details BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01126

21059682

details UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB01126

21059682

details

Abnormal Concentrations

Not Available Associated Disorders and Diseases Disease References

None Associated OMIM IDs

None External Links DrugBank ID

DB01126 DrugBank Metabolite ID

Not Available Phenol Explorer Compound ID

Not Available Phenol Explorer Metabolite ID

Not Available FoodDB ID

Not Available KNApSAcK ID

Not Available Chemspider ID

5293502 KEGG Compound ID

Not Available BioCyc ID

Not Available BiGG ID

Not Available Wikipedia Link

Dutasteride NuGOwiki Link

HMDB15258 Metagene Link

HMDB15258 METLIN ID

Not Available PubChem Compound

6918296 PDB ID

Not Available ChEBI ID

521033

Product: γ-GT

References Synthesis Reference Not Available Material Safety Data Sheet (MSDS) Not Available General References

1. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [PubMed:18318566 ]
2. Shah SK, Trump DL, Sartor O, Tan W, Wilding GE, Mohler JL: Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy. J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16. [PubMed:19091347 ]

Enzymes

General function:

Involved in 3-oxo-5-alpha-steroid 4-dehydrogenase activity

Specific function:

Converts testosterone (T) into 5-alpha-dihydrotestosterone (DHT) and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.

Gene Name:

SRD5A2

Uniprot ID:

P31213

Molecular weight:

28407.035

References

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
2. Rathnayake D, Sinclair R: Male androgenetic alopecia. Expert Opin Pharmacother. 2010 Jun;11(8):1295-304. doi: 10.1517/14656561003752730. [PubMed:20426708 ]
3. Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M: An overview on 5alpha-reductase inhibitors. Steroids. 2010 Feb;75(2):109-53. doi: 10.1016/j.steroids.2009.10.005. Epub 2009 Oct 30. [PubMed:19879888 ]
4. Smith AB, Carson CC: Finasteride in the treatment of patients with benign prostatic hyperplasia: a review. Ther Clin Risk Manag. 2009 Jun;5(3):535-45. Epub 2009 Jul 12. [PubMed:19707263 ]
5. Goldenberg L, So A, Fleshner N, Rendon R, Drachenberg D, Elhilali M: The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme? Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14. [PubMed:19543428 ]
6. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [PubMed:18318566 ]
7. Xu Y, Dalrymple SL, Becker RE, Denmeade SR, Isaacs JT: Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res. 2006 Jul 1;12(13):4072-9. [PubMed:16818707 ]
8. Rittmaster RS, Fleshner NE, Thompson IM: Pharmacological approaches to reducing the risk of prostate cancer. Eur Urol. 2009 May;55(5):1064-73. doi: 10.1016/j.eururo.2009.01.037. Epub 2009 Feb 5. [PubMed:19200641 ]
9. Shah SK, Trump DL, Sartor O, Tan W, Wilding GE, Mohler JL: Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy. J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16. [PubMed:19091347 ]

General function:

Involved in 3-oxo-5-alpha-steroid 4-dehydrogenase activity

Specific function:

Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.

Gene Name:

SRD5A1

Uniprot ID:

P18405

Molecular weight:

29458.18

References

1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
2. Xu Y, Dalrymple SL, Becker RE, Denmeade SR, Isaacs JT: Pharmacologic basis for the enhanced efficacy of dutasteride against prostatic cancers. Clin Cancer Res. 2006 Jul 1;12(13):4072-9. [PubMed:16818707 ]
3. Rathnayake D, Sinclair R: Male androgenetic alopecia. Expert Opin Pharmacother. 2010 Jun;11(8):1295-304. doi: 10.1517/14656561003752730. [PubMed:20426708 ]
4. Aggarwal S, Thareja S, Verma A, Bhardwaj TR, Kumar M: An overview on 5alpha-reductase inhibitors. Steroids. 2010 Feb;75(2):109-53. doi: 10.1016/j.steroids.2009.10.005. Epub 2009 Oct 30. [PubMed:19879888 ]
5. Smith AB, Carson CC: Finasteride in the treatment of patients with benign prostatic hyperplasia: a review. Ther Clin Risk Manag. 2009 Jun;5(3):535-45. Epub 2009 Jul 12. [PubMed:19707263 ]
6. Goldenberg L, So A, Fleshner N, Rendon R, Drachenberg D, Elhilali M: The role of 5-alpha reductase inhibitors in prostate pathophysiology: Is there an additional advantage to inhibition of type 1 isoenzyme? Can Urol Assoc J. 2009 Jun;3(3 Suppl 2):S109-14. [PubMed:19543428 ]
7. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [PubMed:18318566 ]
8. Rittmaster RS, Fleshner NE, Thompson IM: Pharmacological approaches to reducing the risk of prostate cancer. Eur Urol. 2009 May;55(5):1064-73. doi: 10.1016/j.eururo.2009.01.037. Epub 2009 Feb 5. [PubMed:19200641 ]
9. Shah SK, Trump DL, Sartor O, Tan W, Wilding GE, Mohler JL: Phase II study of Dutasteride for recurrent prostate cancer during androgen deprivation therapy. J Urol. 2009 Feb;181(2):621-6. doi: 10.1016/j.juro.2008.10.014. Epub 2008 Dec 16. [PubMed:19091347 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.

Gene Name:

CYP3A4

Uniprot ID:

P08684

Molecular weight:

57255.585

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

General function:

Involved in monooxygenase activity

Specific function:

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.

Gene Name:

CYP3A5

Uniprot ID:

P20815

Molecular weight:

57108.065

References

1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]

PMID: 17620362

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