Dutasteride

Identification

Summary

Dutasteride is an antiandrogenic compound that is used for the treatment of symptomatic benign prostatic hyperplasia (BPH) in adult males by inhibiting 5-alpha reductase.

Brand Names
Avodart, Jalyn
Generic Name
Dutasteride
DrugBank Accession Number
DB01126
Background

Dutasteride is an oral synthetic 4-azasteroid commonly marketed under the trade name Avodart. It is a novel dual 5α-reductase inhibitor that works by blocking both isoforms of 5α-reductase enzymes in a potent, selective, and irreversible manner.1 Type I and II 5α-reductase enzymes convert testosterone into dihydrotestosterone (DHT), a primary hormonal mediator that plays a role in the development and enlargement of the prostate gland. Dutasteride was approved by the FDA in 2001 for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men as monotherapy or in combination with the α-adrenergic antagonist tamsulosin to enhance the therapeutic response. Its clinical efficacy against benign prostate hyperplasia in male patients is comparable to that of finasteride, a specific type II 5α-reductase inhibitor. However, unlike finasteride, dutasteride is not yet indicated for the treatment of androgenic alopecia although it was demonstrated to be effective in several randomized, double-blind, placebo-controlled trials in androgenetic alopecia.3,4

Type
Small Molecule
Groups
Approved, Investigational
Structure
Weight
Average: 528.5297
Monoisotopic: 528.221147444
Chemical Formula
C27H30F6N2O2
Synonyms
  • (5α,17β)-N-(2,5-bis(trifluoromethyl)phenyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide
  • Dutasterida
  • Dutasteride
  • α,α,α,α',α',α'-hexafluoro-3-oxo-4-aza-5α-androst-1-ene-17β-carboxy-2',5'-xylidide
External IDs
  • GG-745
  • GI 198745
  • GI-198745

Pharmacology

Indication

Indicated 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 BPH-related surgery alone or in combination with tamsulosin.15

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofBenign prostatic hyperplasia••••••••••••
Used in combination to manageSymptomatic benign prostatic hyperplasiaCombination Product in combination with: Tamsulosin (DB00706)•••••••••••••••••••• ••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Dutasteride is a synthetic 4-azasteroid compound that selectively inhibits both the type I and type II isoforms of steroid 5α-reductase, an intracellular enzyme that converts testosterone to 5α-dihydrotestosterone (DHT). Dutasteride works by reducing the levels of circulating DHT. It was also shown to reduce the size of the prostate gland, improve urinary flow, and symptoms of benign prostatic hyperplasia alone or in combination with tamsulosin.14 The effect of the reduction of DHT by dutasteride is dose-dependent, with the maximum effect observed within 1-2 weeks following initial administration.15

After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively.15 The serum concentrations of DHT were maintained to be decreased by more than 90% in 85% of patients following 1 years' administration of oral dutasteride 0.5 mg/day.5 As evident from the clinical studies, dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.15

Mechanism of action

The 5α-reductase is a nuclear-bound steroid intracellular enzyme primarily located in the prostatic stromal cell that converts the androgen testosterone into the more active metabolite, 5α-dihydrotestosterone (DHT).7 DHT is considered to be the primary androgen playing a role in the initial development and subsequent enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland.8 DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone13 and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation.9 Responsible for the synthesis of approximately one-third of circulating DHT, type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including the scalp, and liver. The type II 5a-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT.15 Due to its dual inhibition of both isoenzymes of 5α-reductase, dutasteride causes a near-complete suppression of DHT.6 Compared to a 70% reduction of serum DHT levels caused by finasteride, a near-complete suppression of serum DHT-more than 90% is seen with dutasteride.12

By forming a stable complex with both type II and type II 5α-reductase, dutasteride inhibits its enzymatic action of converting testosterone to 5α-dihydrotestosterone (DHT), which is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. It is proposed that DHT is the principal androgen responsible for prostatic growth in later life-normal masculinization of the external genitalia and maturation of the prostate gland during development-thus reducing the serum DHT levels results in reduced prostatic volume and increased epithelial apoptosis.11 Dutasteride is a competitive and specific inhibitor of both Type I and Type II 5α-reductase isoenzymes and when evaluated under in vitro and in vivo conditions, the dissociation of the drug from the drug-enzyme complex is reported to be extremely slow.15 Dutasteride does not bind to the human androgen receptor.15

TargetActionsOrganism
A3-oxo-5-alpha-steroid 4-dehydrogenase 1
inhibitor
Humans
A3-oxo-5-alpha-steroid 4-dehydrogenase 2
inhibitor
Humans
Absorption

Following oral administration of a single dose of 0.5 mg dutasteride, the peak serum concentrations were reached within 2 to 3 hours. Following daily oral administration of 0.5 mg dutasteride, the steady-state concentration of 40 ng/mL is expected to be achieved at 6 months following initial administration. In healthy subjects, the absolute bioavailability was 60%, ranging from 40% to 94%. While food intake reduced the maximum serum concentrations by 10 to 15%, food intake is reported to have a negligible effect on the bioavailability of the drug.15

Volume of distribution

Dutasteride displays a large volume of distribution ranging from 300 to 500 L. Following daily oral administration of 0.5 mg dutasteride healthy subjects for 12 months, the semen dutasteride concentrations averaged 3.4 ng/mL (range: 0.4 to 14 ng/mL) with 11.5% of serum dutasteride concentrations being partitioned into semen.15

Protein binding

Dutasteride is about 99% bound to albumin and 96.6% bound to α-1 acid glycoprotein in the serum.15

Metabolism

Dutasteride undergoes extensive hepatic metabolism mediated by CYP3A4 and CYP3A5. 4′-hydroxydutasteride, 6-hydroxydutasteride, 6,4′-dihydroxydutasteride, 1,2-dihydrodutasteride, and 15-hydroxydutasteride metabolites are formed. 2 minor metabolites - 6,4′-dihydroxydutasteride and 15-hydroxydutasteride - can also be detected. According to in vitro studies, 4′-hydroxydutasteride and 1,2-dihydrodutasteride mediated inhibitory actions against both isoforms of 5α-reductase but with lower potency when compared to the parent drug. The activity of 6β-hydroxydutasteride is comparable to that of dutasteride.15

Route of elimination

Dutasteride and its metabolites mainly undergo fecal excretion. About 1-15% of the dose is excreted as the unchanged parent compound, while 2-90% of the total dose is excreted in the form of dutasteride-related metabolites in the feces. Trace amounts of unchanged dutasteride, with less than 1%, can also be detected in the urine. Therefore, on average, the dose unaccounted for approximated 55%, with a range between 5% and 97%.15

Half-life

The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. This long half-life accounts for the serum concentrations remaining detectable for up to 4 to 6 months after discontinuation of treatment.15

Clearance

In a study of healthy volunteers receiving single oral doses of dutasteride ranging from 0.01 to 40 mg, dutasteride displayed a low linear clearance of 0.58 L/h. The estimated inter-individual variability for the linear clearance was high.10

Adverse Effects
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Toxicity

LD50 values

The estimated dermal LD50 of dutasteride in rabbits is > 2,000 mg/kg.14

Overdose

In studies of volunteers receiving single doses of dutasteride up to 40 mg (which is 80 times the therapeutic dose) for 7 days, there were no reports of clinically significant adverse events.15 Low incidences of impotence, reduced libido, gynecomastia, and ejaculation disorder occurred significantly more often in dutasteride than placebo recipients.5 There are no known antidotes for dutasteride. In case of overdose, appropriate symptomatic and supportive treatment should be given.15

Nonclinical Toxicology

In a 2-year carcinogenicity mouse study, there was an increased incidence of benign hepatocellular adenomas in female mice receiving 250 mg/kg/day.15 An increased incidence of Leydig cell hyperplasia was observed in male rats receiving doses of 7.5 mg/kg/day and greater. At tumorogenic doses, the luteinizing hormone (LH) levels in rats were increased by 167%. There was no demonstrated a genotoxic potential of dutasteride or its metabolites in a bacterial mutagenesis assay, a chromosomal aberration assay in CHO cells, and a micronucleus assay in rats.15 At much higher doses than the maximum recommended human dose (MRHD) in sexually mature male rats, dutasteride caused a dose- and time-dependent decrease in fertility, reduced cauda epididymal (absolute) sperm counts but not sperm concentration (at 50 and 500 mg/kg/day), reduced weights of the epididymis, prostate, and seminal vesicles, and microscopic changes in the male reproductive organs.15 At exposures 425- and 315-fold the expected clinical exposure of dutasteride in rats and dogs, respectively, there were some signs of non-specific, reversible, centrally-mediated toxicity without associated histopathological changes. 15

Pregnancy and Lactation

As DHT is a necessary hormone for the development of male genitalia, exposure to dutasteride in pregnant women bearing male fetuses may cause fetal harm.15 In animal reproduction and developmental toxicity studies, dutasteride inhibited normal development of external genitalia in male fetuses.15 Although it is not known whether dutasteride is excreted in human milk, the use of dutasteride in women of childbearing potential, including nursing women.15 In elderly patients, the half-life of dutasteride may increase. As the renal elimination of dutasteride is very minimal, the use of dutasteride in patients renal insufficiency is reported to be safe.14 There are no specific dosage adjustment recommendations for use in elderly patients or patients with renal impairment.15

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbataceptThe metabolism of Dutasteride can be increased when combined with Abatacept.
AcalabrutinibThe metabolism of Dutasteride can be decreased when combined with Acalabrutinib.
AcebutololDutasteride may decrease the antihypertensive activities of Acebutolol.
AceclofenacThe risk or severity of hypertension can be increased when Dutasteride is combined with Aceclofenac.
AcemetacinThe risk or severity of hypertension can be increased when Dutasteride is combined with Acemetacin.
Food Interactions
  • Take with or without food. The absorption is unaffected by food.

Products

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Product Images
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act DutasterideCapsule0.5 mgOralTEVA Canada Limited2014-09-05Not applicableCanada flag
AvodartCapsule, liquid filled0.5 mg/1OralA-S Medication Solutions2002-12-10Not applicableUS flag
AvodartCapsule, liquid filled0.5 mg/1OralWaylis Therapeutics LLC2022-12-15Not applicableUS flag
AvodartCapsule, liquid filled0.5 mg/1OralWoodward Pharma Services Llc2022-12-15Not applicableUS flag
AvodartCapsule, liquid filled0.5 mg/1OralPreferreed Pharmaceuticals Inc.2002-12-102013-11-30US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Ag-dutasterideCapsule0.5 mgOralAngita Pharma Inc.Not applicableNot applicableCanada flag
Apo-dutasterideCapsule0.5 mgOralApotex Corporation2014-07-18Not applicableCanada flag
Auro-dutasterideCapsule0.5 mgOralAuro Pharma Inc2018-06-04Not applicableCanada flag
DutasterideCapsule, liquid filled0.5 mg/1OralIntergel Pharmaceuticals Inc2002-12-10Not applicableUS flag
DutasterideCapsule0.5 mg/1OralAvKARE, Inc.2015-11-302018-11-01US flag
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Aglandin comp. 0,5 mg/0,4 mg-HartkapselnDutasteride (0.5 mg) + Tamsulosin hydrochloride (0.4 mg)CapsuleOralG.L. Pharma Gmb H2019-01-16Not applicableAustria flag
Bakumokon 5% MinoxidilDutasteride (0.1 mg/100mg) + Minoxidil (5 mg/100mg) + Oxytocin (0.01 mg/100mg)LiquidTopicalDS LABORATORIES, INC.2015-02-092017-10-19US flag
Bakumokon 7% Minoxidil SulfateDutasteride (0.1 mg/100mg) + Minoxidil sulfate (7 mg/100mg) + Oxytocin (0.01 mg/100mg)LiquidTopicalDS LABORATORIES, INC.2015-02-092017-10-11US flag
DUODARTDutasteride (0.5 MG) + Tamsulosin (0.4 MG)CapsuleOralบริษัท แกล็กโซสมิทไคล์น (ประเทศไทย) จำกัด2018-09-24Not applicableThailand flag
DUODART 0,5 MG/0,4 MG KAPSÜL,30 KAPSÜLDutasteride (0.5 mg) + Tamsulosin hydrochloride (0.4 mg)CapsuleOralGLAXOSMİTHKLİNE İLAÇLARI SAN. VE TİC. A.Ş.2020-08-142020-05-22Turkey flag

Categories

ATC Codes
G04CB02 — DutasterideG04CA52 — Tamsulosin and dutasteride
Drug Categories
Chemical TaxonomyProvided by Classyfire
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 masculine characteristics. They also show profound effects on scalp and body hair in humans.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
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
show 5 more
Substituents
3-oxo-4-azasteroid / 3-oxo-5-alpha-steroid / 3-oxosteroid / 4-azasteroid / Alkyl fluoride / Alkyl halide / Androgen-skeleton / Anilide / Aromatic heteropolycyclic compound / Azacycle
show 21 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
delta-lactam, aza-steroid, (trifluoromethyl)benzenes (CHEBI:521033)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
O0J6XJN02I
CAS number
164656-23-9
InChI Key
JWJOTENAMICLJG-QWBYCMEYSA-N
InChI
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
IUPAC Name
(4aR,4bS,6aS,7S,9aS,9bS,11aR)-N-[2,5-bis(trifluoromethyl)phenyl]-4a,6a-dimethyl-2-oxo-1H,2H,4aH,4bH,5H,6H,6aH,7H,8H,9H,9aH,9bH,10H,11H,11aH-indeno[5,4-f]quinoline-7-carboxamide
SMILES
[H][C@@]1(CC[C@@]2([H])[C@]3([H])CC[C@@]4([H])NC(=O)C=C[C@]4(C)[C@@]3([H])CC[C@]12C)C(=O)NC1=CC(=CC=C1C(F)(F)F)C(F)(F)F

References

Synthesis Reference

Manne Reddy, "Forms of dutasteride and methods for preparation thereof." U.S. Patent US20040077673, issued April 22, 2004.

US20040077673
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. [Article]
  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. [Article]
  3. Arif T, Dorjay K, Adil M, Sami M: Dutasteride in Androgenetic Alopecia: An Update. Curr Clin Pharmacol. 2017;12(1):31-35. doi: 10.2174/1574884712666170310111125. [Article]
  4. Shanshanwal SJ, Dhurat RS: Superiority of dutasteride over finasteride in hair regrowth and reversal of miniaturization in men with androgenetic alopecia: A randomized controlled open-label, evaluator-blinded study. Indian J Dermatol Venereol Leprol. 2017 Jan-Feb;83(1):47-54. doi: 10.4103/0378-6323.188652. [Article]
  5. Evans HC, Goa KL: Dutasteride. Drugs Aging. 2003;20(12):905-16; discussion 917-8. doi: 10.2165/00002512-200320120-00005. [Article]
  6. Djavan B, Milani S, Fong YK: Dutasteride: a novel dual inhibitor of 5alpha-reductase for benign prostatic hyperplasia. Expert Opin Pharmacother. 2005 Feb;6(2):311-7. doi: 10.1517/14656566.6.2.311 . [Article]
  7. 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. [Article]
  8. Wilson JD: The pathogenesis of benign prostatic hyperplasia. Am J Med. 1980 May;68(5):745-56. [Article]
  9. Carson C 3rd, Rittmaster R: The role of dihydrotestosterone in benign prostatic hyperplasia. Urology. 2003 Apr;61(4 Suppl 1):2-7. [Article]
  10. Gisleskog PO, Hermann D, Hammarlund-Udenaes M, Karlsson MO: The pharmacokinetic modelling of GI198745 (dutasteride), a compound with parallel linear and nonlinear elimination. Br J Clin Pharmacol. 1999 Jan;47(1):53-8. [Article]
  11. Thomson A: Dutasteride: an evidence-based review of its clinical impact in the treatment of benign prostatic hyperplasia. Core Evid. 2005;1(2):143-56. Epub 2005 Jun 30. [Article]
  12. Marihart S, Harik M, Djavan B: Dutasteride: a review of current data on a novel dual inhibitor of 5alpha reductase. Rev Urol. 2005 Fall;7(4):203-10. [Article]
  13. 34. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 424). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
  14. Avodart (dutasteride capsules) - Product Monograph [Link]
  15. FDA Approved Drug Products: AVODART (dutasteride) capsules [Link]
  16. FDA Approved Drug Products: JALYN (dutasteride and tamsulosin hydrochloride) capsules [Link]
Human Metabolome Database
HMDB0015258
KEGG Drug
D03820
PubChem Compound
6918296
PubChem Substance
46504830
ChemSpider
5293502
BindingDB
50340481
RxNav
228790
ChEBI
521033
ChEMBL
CHEMBL1200969
ZINC
ZINC000003932831
Therapeutic Targets Database
DAP000044
PharmGKB
PA164749300
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Dutasteride
MSDS
Download (37 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentAlcohol Abuse / Alcohol Dependency2
4CompletedTreatmentBenign Prostatic Hyperplasia (BPH)4
4CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Hypogonadisms1
4CompletedTreatmentBenign Prostatic Hyperplasia (BPH) / Prostate Cancer1
4CompletedTreatmentHealthy Volunteers (HV)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Catalent Pharma Solutions
  • GlaxoSmithKline Inc.
  • Letco Medical Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Resource Optimization and Innovation LLC
  • Santec Chemicals Corp.
Dosage Forms
FormRouteStrength
CapsuleOral0.500 mg
Capsule, liquid filledOral0.5 mg/1
LiquidTopical
CapsuleOral
CapsuleOral0.5 mg/1
Capsule, gelatin coatedOral0.5 mg
Capsule, liquid filledOral0.5 mg
CapsuleOral
Capsule, extended releaseOral
CapsuleOral0.4 MG
Capsule, delayed release pelletsOral
Capsule, coatedOral
CapsuleOral0.500 mg
CapsuleOral0.5 mg
Prices
Unit descriptionCostUnit
Avodart 0.5 mg capsule4.12USD capsule
Avodart 0.5 mg softgel4.06USD softgel capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5846976No1998-12-082013-09-17US flag
CA2171329No2004-11-232014-09-16Canada flag
CA2170047No2004-11-092014-09-16Canada flag
US5565467No1996-10-152015-11-20US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)242-250MSDS, FDA Label
water solubilityInsolubleMSDS
logP6.8Human Metabolome Database
Predicted Properties
PropertyValueSource
Water Solubility0.000908 mg/mLALOGPS
logP5.45ALOGPS
logP5.79Chemaxon
logS-5.8ALOGPS
pKa (Strongest Acidic)12.56Chemaxon
pKa (Strongest Basic)-0.16Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count2Chemaxon
Polar Surface Area58.2 Å2Chemaxon
Rotatable Bond Count4Chemaxon
Refractivity127.9 m3·mol-1Chemaxon
Polarizability49.92 Å3Chemaxon
Number of Rings5Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9884
Caco-2 permeable-0.5223
P-glycoprotein substrateSubstrate0.747
P-glycoprotein inhibitor IInhibitor0.7278
P-glycoprotein inhibitor IINon-inhibitor0.6085
Renal organic cation transporterNon-inhibitor0.8299
CYP450 2C9 substrateNon-substrate0.8077
CYP450 2D6 substrateNon-substrate0.9117
CYP450 3A4 substrateSubstrate0.7186
CYP450 1A2 substrateNon-inhibitor0.8089
CYP450 2C9 inhibitorInhibitor0.5412
CYP450 2D6 inhibitorNon-inhibitor0.8391
CYP450 2C19 inhibitorInhibitor0.6287
CYP450 3A4 inhibitorNon-inhibitor0.6506
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5913
Ames testNon AMES toxic0.6677
CarcinogenicityNon-carcinogens0.9149
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6885 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9829
hERG inhibition (predictor II)Non-inhibitor0.574
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0r00-0695380000-37d765dda5ec5e49b0fd
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-056r-0000090000-bd3cd94b010cd745508a
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-004i-0001190000-3f0ab5bc41f7a2208da4
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-00b9-0284790000-aede9dab4286ec28a7c0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-056r-0010090000-977d28d12e47575f6648
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-056s-0100590000-769aec2bfcc79feaa04f
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-00di-0697450000-2abbb12a99ae5e2af3d8
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-222.2239267
predicted
DarkChem Lite v0.1.0
[M-H]-215.29892
predicted
DeepCCS 1.0 (2019)
[M+H]+220.9456267
predicted
DarkChem Lite v0.1.0
[M+H]+217.19432
predicted
DeepCCS 1.0 (2019)
[M+Na]+219.5823267
predicted
DarkChem Lite v0.1.0
[M+Na]+223.18266
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Electron carrier 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 andro...
Gene Name
SRD5A1
Uniprot ID
P18405
Uniprot Name
3-oxo-5-alpha-steroid 4-dehydrogenase 1
Molecular Weight
29458.18 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  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. [Article]
  3. Rathnayake D, Sinclair R: Male androgenetic alopecia. Expert Opin Pharmacother. 2010 Jun;11(8):1295-304. doi: 10.1517/14656561003752730. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  7. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [Article]
  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. [Article]
  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. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Sterol 5-alpha reductase 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...
Gene Name
SRD5A2
Uniprot ID
P31213
Uniprot Name
3-oxo-5-alpha-steroid 4-dehydrogenase 2
Molecular Weight
28393.015 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
  2. Rathnayake D, Sinclair R: Male androgenetic alopecia. Expert Opin Pharmacother. 2010 Jun;11(8):1295-304. doi: 10.1517/14656561003752730. [Article]
  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. [Article]
  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. [Article]
  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. [Article]
  6. Keam SJ, Scott LJ: Dutasteride: a review of its use in the management of prostate disorders. Drugs. 2008;68(4):463-85. [Article]
  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. [Article]
  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. [Article]
  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. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Oxygen binding
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 un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Avodart (dutasteride capsules) - Product Monograph [Link]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Binder
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...
Gene Name
ORM1
Uniprot ID
P02763
Uniprot Name
Alpha-1-acid glycoprotein 1
Molecular Weight
23511.38 Da

Transporters

Kind
Protein
Organism
Mouse
Pharmacological action
Unknown
Actions
Binder
General Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Specific Function
Dopamine binding
Gene Name
Slc6a3
Uniprot ID
Q61327
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68804.71 Da
References
  1. Litim N, Bourque M, Al Sweidi S, Morissette M, Di Paolo T: The 5alpha-reductase inhibitor Dutasteride but not Finasteride protects dopamine neurons in the MPTP mouse model of Parkinson's disease. Neuropharmacology. 2015 Oct;97:86-94. doi: 10.1016/j.neuropharm.2015.05.015. Epub 2015 May 23. [Article]
Kind
Protein
Organism
Mouse
Pharmacological action
Unknown
Actions
Binder
General Function
Involved in the ATP-dependent vesicular transport of biogenic amine neurotransmitters. Pumps cytosolic monoamines including dopamine, norepinephrine, serotonin, and histamine into synaptic vesicles. Requisite for vesicular amine storage prior to secretion via exocytosis (By similarity).
Specific Function
Amine transmembrane transporter activity
Gene Name
Slc18a2
Uniprot ID
Q8BRU6
Uniprot Name
Synaptic vesicular amine transporter
Molecular Weight
55753.05 Da
References
  1. Litim N, Bourque M, Al Sweidi S, Morissette M, Di Paolo T: The 5alpha-reductase inhibitor Dutasteride but not Finasteride protects dopamine neurons in the MPTP mouse model of Parkinson's disease. Neuropharmacology. 2015 Oct;97:86-94. doi: 10.1016/j.neuropharm.2015.05.015. Epub 2015 May 23. [Article]

Drug created at June 13, 2005 13:24 / Updated at March 18, 2024 16:48