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Identification
Name Finasteride
Accession Number DB01216 (APRD00632, DB07774)
Type small molecule
Groups approved
Description

An orally active testosterone 5-alpha-reductase inhibitor. It is used as a surgical alternative for treatment of benign prostatic hyperplasia. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Finasterida [INN-Spanish]
  • Finasteridum [INN-Latin]
Brand names
  • Chibro-Proscar
  • Finastid
  • Finpecia
  • Propecia
  • Proscar
  • Prostide
Brand name mixtures Not Available
Categories
  • Enzyme Inhibitors
  • Skin and Mucous Membrane Agents
  • Anti-baldness Agents
  • Antihyperplasia Agents
CAS number 98319-26-7
Weight Average: 372.5441
Monoisotopic: 372.277678406
Chemical Formula C23H36N2O2
InChI Key InChIKey=DBEPLOCGEIEOCV-WSBQPABSSA-N
InChI
InChI=1S/C23H36N2O2/c1-21(2,3)25-20(27)17-8-7-15-14-6-9-18-23(5,13-11-19(26)24-18)16(14)10-12-22(15,17)4/h11,13-18H,6-10,12H2,1-5H3,(H,24,26)(H,25,27)/t14-,15-,16-,17+,18+,22-,23+/m0/s1
Plain Text
IUPAC Name
(1S,2R,7R,10S,11S,14S,15S)-N-tert-butyl-2,15-dimethyl-5-oxo-6-azatetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-3-ene-14-carboxamide
SMILES
[H][C@@]12CC[C@H](C(=O)NC(C)(C)C)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC[C@@]2([H])NC(=O)C=C[C@]12C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
  • Lactams
Substructures
  • Steroids and Steroid Derivatives
  • Alkanes and Alkenes
  • Amino Ketones
  • Carboxylic Acids and Derivatives
  • Heterocyclic compounds
  • Carboxamides and Derivatives
  • Lactams
Pharmacology
Indication 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, reduce the risk of the need for surgery including transurethral resection of the prostate. Also used for the stimulation of regrowth of hair in men with mild to moderate androgenetic alopecia (male pattern alopecia, hereditary alopecia, common male baldness).
Pharmacodynamics Finasteride is a synthetic 4-azasteroid compound. This drug is a competitive and specific inhibitor of Type II 5a-reductase, an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT). Two distinct isozymes are found in mice, rats, monkeys, and humans: Type I and II. Each of these isozymes is differentially expressed in tissues and developmental stages. In humans, 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. Although finasteride is 100-fold more selective for type II 5a-reductase than for the type I isoenzyme, chronic treatment with this drug may have some effect on type I 5a-reductase.
Mechanism of action The mechanism of action of Finasteride is based on its preferential inhibition of Type II 5a-reductase through the formation of a stable complex with the enzyme. Inhibition of Type II 5a-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations, minimal to moderate increase in serum testosterone concentrations, and substantial increases in prostatic testosterone concetrations. As DHT appears to be the principal androgen responsible for stimulation of prostatic growth, a decrease in DHT concentrations will result in a decrease in prostatic volume (approximately 20-30% after 6-24 months of continued therapy). In men with androgenic alopecia, the mechanism of action has not been fully determined, but finasteride has shown to decrease scalp DHT concentration to the levels found in hairy scalp, reduce serum DHT, increase hair regrowth, and slow hair loss.
Absorption Not Available
Volume of distribution
  • 44 to 96 L
Protein binding Approximately 90%
Metabolism

Drug is extensively metabolized, primarily in the liver via CYP3A4. Two metabolites have been identified with ≤20% of the activity of finasteride.

Enzyme Metabolite Reaction Km Vmax
Cytochrome P450 3A4 omega-hydroxyfinasteride 0 0
Route of elimination Following an oral dose of 14C-finasteride in man (n = 6), a mean of 39% (range, 32 to 46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51 to 64%) was excreted in the feces. Urinary excretion of metabolites was decreased in patients with renal impairment. This decrease was associated with an increase in fecal excretion of metabolites.
Half life 4.5 hours (range 3.3-13.4 hours)
Clearance
  • 165 mL/min [healthy young subjects]
Toxicity Not Available
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Accord healthcare inc usa
  • Actavis totowa llc
  • Aurobindo pharma ltd
  • Dr reddys laboratories inc
  • Dr reddys laboratories ltd
  • Gedeon richter usa inc
  • Hetero drugs ltd unit iii
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Mylan pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Zydus pharmaceuticals usa inc
  • Merck research laboratories div merck co inc
  • Merck and co inc
Packagers
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Proscar 5 mg tablet 3.64 USD tablet
Finasteride 5 mg tablet 3.19 USD tablet
Propecia 1 mg tablet 2.74 USD tablet
Patents
Country Patent Number Approved Expires
United States 5942519 1998-10-23 2018-10-23
United States 6046183 1994-03-20 2011-03-20
Canada 2173457 1999-03-23 2014-10-11
Canada 1331601 1994-08-23 2011-08-23
Properties
State solid
Melting point 252-254 oC
Experimental Properties
Property Value Source
water solubility 11.7 mg/L PhysProp
logP 4.7 PhysProp
Predicted Properties
Property Value Source
water solubility 1.98e-03 g/l ALOGPS
logP 3.53 ALOGPS
logP 3.07 ChemAxon Molconvert
logS -5.27 ALOGPS
pKa 15.91 ChemAxon Molconvert
hydrogen acceptor count 2 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 58.20 ChemAxon Molconvert
rotatable bond count 2 ChemAxon Molconvert
refractivity 108.20 ChemAxon Molconvert
polarizability 43.93 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  1. Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y: Saturable binding of finasteride to steroid 5alpha-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet. 2010;25(2):208-13. Pubmed
  2. 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
External Links
Resource Link
KEGG Drug D00321 Link_out
PubChem Compound 57363 Link_out
PubChem Substance 46507645 Link_out
ChemSpider 51714 Link_out
ChEBI 5062 Link_out
ChEMBL 5062 Link_out
Therapeutic Targets Database DAP000045 Link_out
HET FIT Link_out
Drug Product Database 2238213 Link_out
RxList http://www.rxlist.com/cgi/generic3/propecia.htm Link_out
Drugs.com http://www.drugs.com/cdi/finasteride.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Finasteride Link_out
ATC Codes
  • D11AX10
  • G04CB01
AHFS Codes
  • 84:92.00
  • 92:00.00
PDB Entries Not Available
FDA label show (103.3 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Food Interactions
  • Take without regard to meals.
Targets

1. 3-oxo-5-alpha-steroid 4-dehydrogenase 2

Pharmacological action: yes
Actions: inhibitor

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

Organism class: human
UniProt ID: P31213 Link_out
Gene: SRD5A2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Bowman CJ, Barlow NJ, Turner KJ, Wallace DG, Foster PM: Effects of in utero exposure to finasteride on androgen-dependent reproductive development in the male rat. Toxicol Sci. 2003 Aug;74(2):393-406. Epub 2003 May 28. Pubmed
  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
  3. Ha SJ, Kim JS, Myung JW, Lee HJ, Kim JW: Analysis of genetic polymorphisms of steroid 5alpha-reductase type 1 and 2 genes in Korean men with androgenetic alopecia. J Dermatol Sci. 2003 Apr;31(2):135-41. Pubmed
  4. Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y: Saturable binding of finasteride to steroid 5alpha-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet. 2010;25(2):208-13. Pubmed
  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
  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
  7. Joseph MA, Jayaseelan E, Ganapathi B, Stephen J: Hidradenitis suppurativa treated with finasteride. J Dermatolog Treat. 2005 Apr;16(2):75-8. Pubmed

2. 3-oxo-5-alpha-steroid 4-dehydrogenase 1

Pharmacological action: unknown
Actions: inhibitor

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

Organism class: human
UniProt ID: P18405 Link_out
Gene: SRD5A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Thigpen AE, Russell DW: Four-amino acid segment in steroid 5 alpha-reductase 1 confers sensitivity to finasteride, a competitive inhibitor. J Biol Chem. 1992 Apr 25;267(12):8577-83. Pubmed
  2. Levy MA, Brandt M, Sheedy KM, Holt DA, Heaslip JI, Trill JJ, Ryan PJ, Morris RA, Garrison LM, Bergsma DJ: Cloning, expression and functional characterization of type 1 and type 2 steroid 5 alpha-reductases from Cynomolgus monkey: comparisons with human and rat isoenzymes. J Steroid Biochem Mol Biol. 1995 Apr;52(4):307-19. Pubmed
  3. Tian G, Stuart JD, Moss ML, Domanico PL, Bramson HN, Patel IR, Kadwell SH, Overton LK, Kost TA, Mook RA Jr, et al.: 17 beta-(N-tert-butylcarbamoyl)-4-aza-5 alpha-androstan-1-en-3-one is an active site-directed slow time-dependent inhibitor of human steroid 5 alpha-reductase 1. Biochemistry. 1994 Mar 1;33(8):2291-6. Pubmed
  4. Suzuki R, Satoh H, Ohtani H, Hori S, Sawada Y: Saturable binding of finasteride to steroid 5alpha-reductase as determinant of nonlinear pharmacokinetics. Drug Metab Pharmacokinet. 2010;25(2):208-13. Pubmed
  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

3. 3-oxo-5-beta-steroid 4-dehydrogenase

Pharmacological action: unknown
Actions: inhibitor

Efficiently catalyzes the reduction of progesterone, androstenedione, 17-alpha-hydroxyprogesterone and testosterone to 5-beta-reduced metabolites. The bile acid intermediates 7- alpha,12-alpha-dihydroxy-4-cholesten-3-one and 7-alpha-hydroxy-4- cholesten-3-one can also act as substrates

Organism class: human
UniProt ID: P51857 Link_out
Gene: AKR1D1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Drury JE, Di Costanzo L, Penning TM, Christianson DW: Inhibition of human steroid 5beta-reductase (AKR1D1) by finasteride and structure of the enzyme-inhibitor complex. J Biol Chem. 2009 Jul 24;284(30):19786-90. Epub 2009 Jun 10. Pubmed
Enzymes

1. Cytochrome P450 3A5

Actions: substrate

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

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

2. Cytochrome P450 3A7

Actions: substrate

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

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.

3. Cytochrome P450 3A4

Actions: substrate

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. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Huskey SW, Dean DC, Miller RR, Rasmusson GH, Chiu SH: Identification of human cytochrome P450 isozymes responsible for the in vitro oxidative metabolism of finasteride. Drug Metab Dispos. 1995 Oct;23(10):1126-35. Pubmed
  3. 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. Epub 2009 Nov 24. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on October 11, 2011 14:37

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.