DUTASTERIDE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C27H30F6N2O2
Molecular Weight	528.5297
Optical Activity	UNSPECIFIED
Defined Stereocenters	7 / 7
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@H](C(=O)NC3=CC(=CC=C3C(F)(F)F)C(F)(F)F)[C@@]1(C)CC[C@@]4([H])[C@@]2([H])CC[C@@]5([H])NC(=O)C=C[C@]45C

InChI

InChIKey=JWJOTENAMICLJG-QWBYCMEYSA-N

InChI=1S/C27H30F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,10,12-13,15-17,19,21H,4,6-9,11H2,1-2H3,(H,34,37)(H,35,36)/t15-,16-,17-,19+,21+,24-,25+/m0/s1

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB01126
Curator's Comment: Description was created based on several sources, including http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021319s028s029lbl.pdf

Dutasteride is a synthetic 4-azasteroid compound that is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 alpha-reductase (5AR), intracellular enzymes that convert testosterone to 5 alpha-dihydrotestosterone (DHT). Type I 5a-reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5a-reductase is responsible for approximately one-third of circulating DHT. The Type II 5a-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. Dutasteride inhibits the conversion of testosterone to 5 alpha-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5 alpha-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate gland to improve symptoms, and reduce the risk of acute urinary retention and the need for surgery. Marketed under the brand name Avodart.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Glycine receptor subunit alpha-1 24 Target ID: CHEMBL5845 Sources: https://www.ncbi.nlm.nih.gov/pubmed/25790278	Modulator 828		0.33 µM [EC50]
Steroid 5-alpha-reductase 15 Target ID: CHEMBL2363075 Sources: https://www.ncbi.nlm.nih.gov/pubmed/20519274	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Benign prostatic hyperplasia 28 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/021319s028s029lbl.pdf	Primary		Approved 8429	AVODART Approved Use AVODART is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: improve symptoms, reduce the risk of acute urinary retention, and reduce the risk of the need for BPH-related surgery. AVODART in combination with the alpha adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate Launch Date 2001

C_max

Value	Dose	Co-administered	Analyte	Population
8.91 ng/mL EXPERIMENT https://link.springer.com/article/10.1365/s10337-008-0613-7	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: TAMSULOSIN	TAMSULOSIN	DUTASTERIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
56.85 ng × h/mL EXPERIMENT https://link.springer.com/article/10.1365/s10337-008-0613-7	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: TAMSULOSIN	TAMSULOSIN	DUTASTERIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.71 h EXPERIMENT https://link.springer.com/article/10.1365/s10337-008-0613-7	0.5 mg single, oral dose: 0.5 mg route of administration: Oral experiment type: SINGLE co-administered: TAMSULOSIN	TAMSULOSIN	DUTASTERIDE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN
35 day REVIEW https://www.ncbi.nlm.nih.gov/pubmed/14565784	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DUTASTERIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.5% REVIEW https://www.ncbi.nlm.nih.gov/pubmed/14565784	0.5 mg 1 times / day steady-state, oral dose: 0.5 mg route of administration: Oral experiment type: STEADY-STATE co-administered:		DUTASTERIDE plasma	Homo sapiens population: UNKNOWN age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587 inducer 781	substrate 1037 inhibitor 1767	substrate 1217 inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2E1 882 CYP2C8 911 CYP2C19 1478 CYP2B6 810 OAT3 642 OATP1B1 788 OATP1B3 706 MRP2 383	CYP3A5 395 CYP1A2 1054 CYP2A6 543 CYP2C19 991 CYP2E1 667

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP1A2 1692	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP2A6 739	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP2C8 965	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP2E1 970	inhibitor 3277 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	no
CYP3A4 1925	inducer 1573 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0	no
MRP2 475	inhibitor 3277 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0	no
OAT3 644	inhibitor 3277 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0	yes [IC50 0.5 uM]	likely (co-administration study) Comment: Adverse events were experienced by subjects; however, none of these events was serious or causally related to dutasteride. Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0
OATP1B1 803	inhibitor 3277 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0	yes [IC50 0.8 uM]	likely (co-administration study) Comment: Adverse events were experienced by subjects; however, none of these events was serious or causally related to dutasteride. Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0
OATP1B3 715	inhibitor 3277 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0	yes [IC50 20 uM]	likely (co-administration study) Comment: Adverse events were experienced by subjects; however, none of these events was serious or causally related to dutasteride. Sources: https://www.pmda.go.jp/files/000220574.pdf#page=9 Page: 9.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=8 Page: 8.0	yes [IC50 50 uM]
CYP2C19 1553	inhibitor 3277 Sources: https://www.pmda.go.jp/files/000220574.pdf#page=8 Page: 8.0	yes [IC50 50 uM]	likely (co-administration study) Comment: Adverse events were experienced by subjects; however, none of these events was serious or causally related to dutasteride. Sources: https://www.pmda.go.jp/files/000220574.pdf#page=8 Page: 8.0

Drug as victim

Target	Modality	Activity
CYP1A2 1054	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	no
CYP2A6 543	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	no
CYP2C19 991	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	no
CYP2C9 1037	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	no
CYP2D6 1217	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	no
CYP2E1 667	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	no
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2001/21319_Duagen_biopharmr_P1.pdf#page=7 Page: 7.0	yes
CYP3A5 395	substrate 3367 Sources: https://ca.gsk.com/media/588688/avodart.pdf#page=13 Page: 13.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:521033	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:521033
ChemicalBook	CB3254628	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB3254628
MolPort	MolPort-003-847-041	https://www.molport.com/shop/molecule-link/MolPort-003-847-041
Selleck Chemicals	Dutasteride	http://www.selleckchem.com/products/Dutasteride.html
ZINC	ZINC000003932831	http://zinc15.docking.org/substances/ZINC000003932831
eMolecules	8724782	https://www.emolecules.com/cgi-bin/more?vid=8724782

PubMed

Title	Date	PubMed
[Dutasteride: main results in the treatment of benign prostatic hyperplasia].	2004 Dec	15651494
[Use of 5-alpha-reductase inhibitors in the prevention of prostate cancer].	2004 Dec	15651489
Preventing diseases of the prostate in the elderly using hormones and nutriceuticals.	2004 Jun	15672940
Gateways to clinical trials.	2004 Nov	15632957
Chemoprevention of prostate cancer in men at high risk: rationale and design of the reduction by dutasteride of prostate cancer events (REDUCE) trial.	2004 Oct	15371831
Gateways to clinical trials.	2005 Apr	15834452
Chemoprevention of prostate cancer.	2005 Apr	15780904
RE: Effect of the dual 5alpha-reductase inhibitor dutasteride on markers of tumor regression in prostate cancer.	2005 Apr	15758829
Selecting therapy for maintaining sexual function in patients with benign prostatic hyperplasia.	2005 Aug	16042709
[Effect of dutasteride on reduction of plasma DHT following finasteride therapy in patients with benign prostatic hyperplasia].	2005 Dec	16429658
[Effect of dutasteride on reduction of intraoperative bleeding related to transurethral resection of the prostate].	2005 Dec	16429657
Gateways to clinical trials.	2005 Dec	16395422
Noninvasive management of lower urinary tract symptoms and sexual dysfunction associated with benign prostatic hyperplasia in the primary care setting.	2005 Fall	16110128
Dutasteride: a novel dual inhibitor of 5alpha-reductase for benign prostatic hyperplasia.	2005 Feb	15757426
The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate.	2005 Jan	15667867
Chemoprevention using dutasteride: the REDUCE trial.	2005 Jan	15586026
Combined inhibition of types I and II 5 alpha-reductase selectively augments the basal (nonpulsatile) mode of testosterone secretion in young men.	2005 Jul	15811930
Gateways to clinical trials.	2005 Jul-Aug	16179960
Gateways to clinical trials.	2005 Jun	16082422
Pharmacogenetic analysis of human steroid 5 alpha reductase type II: comparison of finasteride and dutasteride.	2005 Jun	15956333
Sexual dysfunction and lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH).	2005 Jun	15925080
[Dutasteride (Avodart): a novel 5-alpha reductase inhibitor for treatment of benign prostate hypertrophy].	2005 Mar-Apr	15945422
Gateways to clinical trials.	2005 May	16082427
Oral testosterone in oil plus dutasteride in men: a pharmacokinetic study.	2005 May	15713724
Effect of dutasteride on the detection of prostate cancer in men with benign prostatic hyperplasia.	2005 Nov	16217336
Phase III prostate cancer prevention trials: are the costs justified?	2005 Nov 10	16278467
Evaluation and medical management of benign prostatic hyperplasia.	2005 Oct	16212149
Effect of dutasteride therapy on Doppler US evaluation of prostate: preliminary results.	2005 Oct	16183933
Effects of testosterone and levonorgestrel combined with a 5alpha-reductase inhibitor or gonadotropin-releasing hormone antagonist on spermatogenesis and intratesticular steroid levels in normal men.	2005 Oct	16030154
Gateways to clinical trials.	2005 Sep	16258596
[Novel therapeutics strategies in benign hypertrophy of prostate management].	2005 Sep	16240894
Long-term sustained improvement in symptoms of benign prostatic hyperplasia with the dual 5alpha-reductase inhibitor dutasteride: results of 4-year studies.	2005 Sep	16104912
[Prevention of prostate cancer].	2005 Sep 9	16143928
Effective treatment of female androgenic alopecia with dutasteride.	2005 Sep-Oct	16167423
Discovery and clinical development of dutasteride, a potent dual 5alpha-reductase inhibitor.	2006	16719800
Inhibitors of 5alpha-reductase in the treatment of benign prostatic hyperplasia.	2006	16515494
Treatment and pharmacologic management of BPH in the context of common comorbidities.	2006 Apr	16613527
BPH: epidemiology and comorbidities.	2006 Apr	16613526
Dutasteride: a dual 5-alpha reductase inhibitor for the treatment of symptomatic benign prostatic hyperplasia.	2006 Apr	16569804
Relationship among serum testosterone, sexual function, and response to treatment in men receiving dutasteride for benign prostatic hyperplasia.	2006 Apr	16434455
Dutasteride, cantharidin, atopiclair, cetuximab, sirolimus, AC-11 and dimericine reviewed in brief.	2006 Feb	16485893
Treatment of lower urinary tract symptoms in benign prostatic hyperplasia and its impact on sexual function.	2006 Jan	16490576
Development of nomogram to predict acute urinary retention or surgical intervention, with or without dutasteride therapy, in men with benign prostatic hyperplasia.	2006 Jan	16413338
Long-term therapy with the dual 5alpha-reductase inhibitor dutasteride is well tolerated in men with symptomatic benign prostatic hyperplasia.	2006 Jan	16336332
Gateways to clinical trials.	2006 Jan-Feb	16541195
Oral testosterone in oil: pharmacokinetic effects of 5alpha reduction by finasteride or dutasteride and food intake in men.	2006 Jan-Feb	16400081
Effects of the dual 5 alpha-reductase inhibitor dutasteride on apoptosis in primary cultures of prostate cancer epithelial cells and cell lines.	2006 Jun 15	16703599
Update on prostate cancer chemoprevention.	2006 Mar	16503715
Gateways to clinical trials.	2006 May	16801985
Clinical usefulness of serum prostate specific antigen for the detection of prostate cancer is preserved in men receiving the dual 5alpha-reductase inhibitor dutasteride.	2006 May	16600723

Patents

Sample Use Guides

In Vivo Use Guide

Monotherapy: 0.5 mg once daily. Combination with tamsulosin: 0.5 mg once daily and tamsulosin 0.4 mg once daily. Dosing considerations: Swallow whole. May take with or without food.

Route of Administration: Oral

In Vitro Use Guide

Both low (0.25 uM) or high (1.0 uM) doses of dutasteride abrogated testosterone-stimulated growth of androgen-sensitive benign BPH-1 cells, LNCaP cancer cells, their derivative C4-2 cells, or Dunning rat cancer cells lines.

Name

Type

Language

DUTASTERIDE

Official Name

English

GI 198745

Code

English

AVOLVE

Common Name

English

DUASTRIDE

Brand Name

English

Dutasteride [WHO-DD]

Common Name

English

(5.ALPHA.,17.BETA.)-N-(2,5-BIS(TRIFLUOROMETHYL)PHENYL)-3-OXO-4-AZAANDROST-1-ENE-17-CARBOXAMIDE

Common Name

English

GG-745

Code

English

.ALPHA.,.ALPHA.,.ALPHA.,.ALPHA.',.ALPHA.',.ALPHA.'-HEXAFLUORO-3-OXO-4-AZA-5.ALPHA.-ANDROST-1-ENE-17.BETA.-CARBOXY-2',5'-XYLIDIDE

Common Name

English

DUTASTERIDE COMPONENT OF JALYN

Brand Name

English

JALYN COMPONENT DUTASTERIDE

Brand Name

English

DUTASTERIDE [USAN]

Common Name

English

dutasteride [INN]

Common Name

English

DUTASTERIDE [MI]

Common Name

English

AVODART

Brand Name

English

DUTASTERIDE [VANDF]

Common Name

English

DUTASTERIDE [USP MONOGRAPH]

Common Name

English

DUTASTERIDE [USP-RS]

Common Name

English

DUTASTERIDE [ORANGE BOOK]

Common Name

English

NSC-740477

Code

English

DUTASTERIDE [MART.]

Common Name

English

DUTASTERIDE [EP MONOGRAPH]

Common Name

English

NSC-759880

Code

English

DUTASTERIDE [JAN]

Common Name

English

GI-198745

Code

English

Classification Tree Code System Code

LIVERTOX

NBK548058