Finasteride (original) (raw)

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Summary

Finasteride is an antiandrogenic compound that is used for the treatment of symptomatic benign prostatic hyperplasia (BPH) and male pattern hair loss in adult males by inhibiting Type II 5-alpha reductase.

Brand Names

Entadfi, Propecia, Proscar

Generic Name

Finasteride

DrugBank Accession Number

DB01216

Background

Finasteride is a synthetic 4-azasteroid compound 13 and specific inhibitor of steroid Type II 5α-reductase, which is an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT). It works in a similar fashion as dutasteride, which is another 5-alpha-reductase inhibitor, by exerting antiandrogenic effects. Finasteride is an orally active drug that was first approved by the FDA in 1992 for the treatment of benign prostatic hyperplasia to improve symptoms and reduce the risk for acute urinary retention or the need for surgical procedures.12,13 In 1998, it was approved by the FDA to treat male pattern hair loss.12 Finasteride is commonly marketed under the brand names Propecia and Proscar to be used aloneo or in combination with doxazosin, an alpha-blocker.

Both benign prostatic hyperplasia and androgenic alopecia are androgen-dependent disorders that are characterized by in situ high levels of DHT.2 In the treatment of benign prostate hyperplasia, alpha-blockers such as tamsulosin and terazosin are also used. Compared to alpha-blockers that focus on providing the rapid relief of symptoms, 5α-reductase inhibitors aim to target the underlying disease by blocking the effects of the primary androgen involved in benign prostate hyperplasia and androgenic alopecia, thus reducing the risk for secondary complications while providing symptom control.1

Type

Small Molecule

Groups

Approved

Structure

Weight

Average: 372.5441
Monoisotopic: 372.277678406

Chemical Formula

C23H36N2O2

Synonyms

• (5alpha,17beta)-(1,1-Dimethylethyl)-3-oxo-4-azaandrost-1-ene-17-carboxamide
• Finasterida
• Finasteride
• Finasteridum

External IDs

• MK-906

Indication

Finasteride 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 surgery including transurethral resection of the prostate (TURP) and prostatectomy.13 A combination product with tadalafil is also used for the symptomatic treatment of BPH for up to 26 weeks.14

Finasteride is also indicated for the treatment of male pattern hair loss (androgenetic alopecia, hereditary alopecia, or common male baldness) in male patients.11

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Associated Conditions

Contraindications & Blackbox Warnings

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Pharmacodynamics

Finasteride is an antiandrogenic compound that works by suppressing the production of serum and intraprostatic dihydrotestosterone (DHT) in men via inhibiting the enzyme responsible for the biosynthesis of DHT. The maximum effect of a rapid reduction in serum DHT concentration is expected to be observed 8 hours following administration of the first dose.13 In a single man receiving a single oral dose of 5 mg finasteride for up to 4 years, there was a reduction in the serum DHT concentrations by approximately 70% and the median circulating level of testosterone increased by approximately 10-20% within the physiologic range. 13 In a double-blind, placebo-controlled study, finasteride reduced intraprostatic DHT level by 91.4% but finasteride is not expected to decrease the DHT levels to castrate levels since circulating testosterone is also converted to DHT by the type 1 isoenzyme expressed in other tissues.1 It is expected that DHT levels return to normal within 14 days upon discontinuation of the drug.12 In a study of male patients with benign prostatic hyperplasia prior to prostatectomy, the treatment with finasteride resulted in an approximate 80% lower DHT content was measured in prostatic tissue removed at surgery compared to placebo.13 While finasteride reduces the size of the prostate gland by 20%, this may not correlate well with improvement in symptoms.8 The effects of finasteride are reported to be more pronounced in male patients with enlarged prostates (>25 mL) who are at the greatest risk of disease progression.1

In phase III clinical studies, oral administration of finasteride in male patients with male pattern hair loss promoted hair growth and prevented further hair loss by 66% and 83% of the subjects, respectively, which lasted during two years' treatment.6 The incidences of these effects in treatment groups were significantly higher than that of the group receiving a placebo.6 Following finasteride administration, the levels of DHT in the scalp skin was shown to be reduced by more than 60%, indicating that the DHT found in scalp is derived from both local DHT production and circulating DHT.5 The effect of finasteride on scalp DHT is likely seen because of its effect on both local follicular DHT levels as well as serum DHT levels.5. There is evidence from early clinical observations and controlled studies that finasteride may reduce bleeding of prostatic origin.3

Mechanism of action

Finasteride acts as a competitive and specific inhibitor of Type II 5α-reductase, 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).1 DHT is considered to be the primary androgen playing a role in the development and enlargement of the prostate gland. It serves as the hormonal mediator for the hyperplasia upon accumulation within the prostate gland.7 DHT displays a higher affinity towards androgen receptors in the prostate gland compared to testosterone10 and by acting on the androgen receptors, DHT modulates genes that are responsible for cell proliferation.9 Responsible for the production of DHT together with type I 5α-reductase, the type II 5α-reductase isozyme is primarily found in the prostate, seminal vesicles, epididymides, and hair follicles as well as liver.11 Although finasteride is 100-fold more selective for type II 5α-reductase than for the type I isoenzyme,3 chronic treatment with this drug may have some effect on type I 5α-reductase, which is predominantly expressed in sebaceous glands of most regions of skin, including the scalp, and liver. It is proposed that the type I 5α-reductase and type II 5α-reductase is responsible for the production of one-third and two-thirds of circulating DHT, respectively.

The mechanism of action of Finasteride is based on its preferential inhibition of Type II 5α-reductase through the formation of a stable complex with the enzyme in vitro and in vivo.13 Finasteride works selectively, where it preferentially displays a 100-fold selectivity for the human Type II 5α-reductase over type I enzyme.11 Inhibition of Type II 5α-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 concentrations. 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). It is suggested that increased levels of DHT can lead to potentiated transcription of prostaglandin D2, which promotes the proliferation of prostate cancer cells.4 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 the hairy scalp, reduce serum DHT, increase hair regrowth, and slow hair loss. Another study suggests that finasteride may work to reduce bleeding of prostatic origin by inhibiting vascular endothelial growth factor (VEGF) in the prostate, leading to atrophy and programmed cell death.3 This may bestow the drug therapeutic benefits in patients idiopathic prostatic bleeding, bleeding during anticoagulation, or bleeding after instrumentation.3

Absorption

Finasteride is well absorbed following oral administration 10 and displays a slow accumulation phase after multiple dosing.[lablel] In healthy male subjects receiving oral finasteride, the mean oral bioavailability was 65% for 1 mg finasteride and 63% for 5 mg finasteride, and the values ranged from 26 to 170% for 1 mg dose and from 34 to 108% for 5 mg dose, respectively.11,13 It is reported that food intake does not affect the oral bioavailability of the drug.5 The peak plasma concentrations (Cmax) averaged 37 ng/mL (range, 27-49 ng/mL) and was reached 1-2 hours post administration.13 The AUC(0-24 hr) was 53 ngxhr/mL (range, 20-154 ngxhr/mL).11 The plasma concentrations and AUC are reported to be higher in elderly male patients aged 70 years or older.11

Volume of distribution

The volume of distribution is 76 L at steady state, ranging from 44 to 96 L. Finasteride has been shown to cross the blood brain barrier but does not appear to distribute preferentially to the CSF.13 It is not known whether finasteride is excreted in human milk.11

Protein binding

Approximately 90% of circulating finasteride is bound to plasma proteins.13

Metabolism

Finasteride undergoes extensive hepatic metabolism predominantly mediated by the cytochrome P450 3A4 (CYP3A4) enzyme to form the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites.5,13 Theses metabolites retain less than 20% of the pharmacological activity of the parent compound.13

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Route of elimination

In healthy subjects, about 32-46% of total oral dose of finasteride was excreted in the urine in the form of metabolites while about 51-64% of the dose was excreted in the feces. In patients with renal impairment, the extent of urinary excretion of finasteride is expected to be decreased while the fecal excretion is increased.13

Half-life

In healthy young subjects receiving finasteride, the mean elimination half-life in plasma was 6 hours ranging from 3 to 16 hours. In elderly patients over the age of 70 years, the half-life is prolonged to 8 hours.13

Clearance

In healthy young subjects (n=15), the mean plasma clearance of finasteride was 165 mL/min with the range between 70 and 279 mL/min.13

Adverse Effects

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Toxicity

LD50

Oral LD50 is about 418 mg/kg in ratsMSDS and there have been cases of lethality in rats receiving a single oral dose of 400 mg/kg in males and 1000 mg/kg in females.13

Nonclinical toxicology

In a 24-month rat study, there were no signs of the tumorigenic potential of finasteride.11 In a 19-month carcinogenicity study in CD-1 mice, high doses of finasteride, at 1824 times the human exposure (250 mg/kg/day), resulted in an increase in the incidence of testicular Leydig cell adenomas and an increase in serum LH levels.11 In vitro mutagenesis assays demonstrated no evidence of mutagenicity. In an in vitro chromosome aberration assay, using Chinese hamster ovary cells, there was a slight increase in chromosome aberrations with much higher doses of finasteride.11

Overdose

There were no reported significant adverse events in clinical trials of male patients receiving single oral doses of finasteride up to 400 mg and multiple doses of finasteride up to 80 mg/day for three months.11 As there have been no cases of overdose or clinically significant toxicity with finasteride, there are no specific recommendations in case of an overdose.13

Significant adverse events

Common reproductive adverse events seen with finasteride therapy include erectile dysfunction, ejaculatory dysfunction, and loss of libido.5 These adverse events tend to disappear after discontinuation or chronic use of the drug. Only causal adverse event occurring at the male reproductive system that is caused by finasteride is decreased ejaculatory volume because of the predominant action of DHT on the prostate.5

Special populations

Finasteride can be safely used in elderly patients or those with renal impairment with no specific dosing adjustment recommendations.13 Finasteride is indicated for male patients only, and it is advised that exposure to finasteride is avoided in pregnant women carrying male fetuses as it may lead to abnormal development of external genitalia in male fetuses.11

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Not Available

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.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Food Interactions

• Take with or without food. The absorption is unaffected by food.

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Product Images

International/Other Brands

Finastid / Finpecia

Brand Name Prescription Products

Generic Prescription Products

Mixture Products

Name	Ingredients	Dosage	Route	Labeller	Marketing Start	Marketing End	Region	Image
Entadfi	Finasteride (5 mg/1) + Tadalafil (5 mg/1)	Capsule	Oral	Veru Inc.	2021-12-12	Not applicable

Unapproved/Other Products

ATC Codes

D11AX10 — Finasteride

• D11AX — Other dermatologicals
• D11A — OTHER DERMATOLOGICAL PREPARATIONS
• D11 — OTHER DERMATOLOGICAL PREPARATIONS
• D — DERMATOLOGICALS G04CA55 — Doxazosin and finasteride
• G04CA — Alpha-adrenoreceptor antagonists
• G04C — DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY
• G04 — UROLOGICALS
• G — GENITO URINARY SYSTEM AND SEX HORMONES G04CA51 — Alfuzosin and finasteride
• G04CA — Alpha-adrenoreceptor antagonists
• G04C — DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY
• G04 — UROLOGICALS
• G — GENITO URINARY SYSTEM AND SEX HORMONES G04CB51 — Finasteride and tadalafil
• G04CB — Testosterone-5-alpha reductase inhibitors
• G04C — DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY
• G04 — UROLOGICALS
• G — GENITO URINARY SYSTEM AND SEX HORMONES G04CB01 — Finasteride
• G04CB — Testosterone-5-alpha reductase inhibitors
• G04C — DRUGS USED IN BENIGN PROSTATIC HYPERTROPHY
• G04 — UROLOGICALS
• G — GENITO URINARY SYSTEM AND SEX HORMONES

Drug Categories

• 5-alpha Reductase Inhibitors
• Adrenergic alpha-Antagonists
• Adrenergic Antagonists
• Agents that produce hypertension
• Androstanes
• Androstenes
• Azasteroids
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A5 Substrates
• Cytochrome P-450 CYP3A7 Substrates
• Cytochrome P-450 Substrates
• Dermatologicals
• Drugs Used in Benign Prostatic Hypertrophy
• Enzyme Inhibitors
• Fused-Ring Compounds
• Genito Urinary System and Sex Hormones
• Genitourinary Agents
• Hormone Antagonists
• Hormones, Hormone Substitutes, and Hormone Antagonists
• Misc. Skin and Mucous Membrane Agents
• Steroid Synthesis Inhibitors
• Steroids
• Urological Agents
• Urologicals

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-hydroxysteroids / 4-azasteroids and derivatives / Cyclic carboximidic acids / Propargyl-type 1,3-dipolar organic compounds / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Hydrocarbon derivatives

Substituents

20-hydroxysteroid / 3-hydroxysteroid / 4-azasteroid / Aliphatic heteropolycyclic compound / Androgen-skeleton / Azacycle / Azasteroid / Carboximidic acid / Carboximidic acid derivative / Cyclic carboximidic acid

Molecular Framework

Aliphatic heteropolycyclic compounds

External Descriptors

3-oxo steroid, aza-steroid (CHEBI:5062)

Affected organisms

• Humans and other mammals

UNII

57GNO57U7G

CAS number

98319-26-7

InChI Key

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

IUPAC Name

(4aR,4bS,6aS,7S,9aS,9bS,11aR)-N-tert-butyl-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@@]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

Synthesis Reference

Roman Davis, Alan Millar, "Method for preparing finasteride." U.S. Patent US5670643, issued October, 1992.

US5670643

General References

1. 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]
2. Agamia NF, Abou Youssif T, El-Hadidy A, El-Abd A: Benign prostatic hyperplasia, metabolic syndrome and androgenic alopecia: Is there a possible relationship? Arab J Urol. 2016 Feb 23;14(2):157-62. doi: 10.1016/j.aju.2016.01.003. eCollection 2016 Jun. [Article]
3. Vaughan ED: Long-Term Experience with 5-alpha-Reductase Inhibitors. Rev Urol. 2003;5 Suppl 4:S28-33. [Article]
4. Bhargava S: Increased DHT levels in androgenic alopecia have been selected for to protect men from prostate cancer. Med Hypotheses. 2014 Apr;82(4):428-32. doi: 10.1016/j.mehy.2014.01.016. Epub 2014 Jan 26. [Article]
5. Mysore V: Finasteride and sexual side effects. Indian Dermatol Online J. 2012 Jan;3(1):62-5. doi: 10.4103/2229-5178.93496. [Article]
6. McClellan KJ, Markham A: Finasteride: a review of its use in male pattern hair loss. Drugs. 1999 Jan;57(1):111-26. doi: 10.2165/00003495-199957010-00014. [Article]
7. Wilson JD: The pathogenesis of benign prostatic hyperplasia. Am J Med. 1980 May;68(5):745-56. [Article]
8. Steiner JF: Clinical pharmacokinetics and pharmacodynamics of finasteride. Clin Pharmacokinet. 1996 Jan;30(1):16-27. doi: 10.2165/00003088-199630010-00002. [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. 34. (2012). In Rang and Dale's Pharmacology (7th ed., pp. 424). Edinburgh: Elsevier/Churchill Livingstone. [ISBN:978-0-7020-3471-8]
11. FDA Approved Drug Products: PROPECIA (finasteride) tablets [Link]
12. Finasteride - StatPearls - NCBI Bookshelf [Link]
13. FDA Approved Drug Products: PROSCAR (finasteride) tablets [Link]
14. FDA Approved Drug Products: Entadfi (finasteride/tadalafil) capsules for oral use [Link]

External Links

Human Metabolome Database

HMDB0001984

KEGG Drug

D00321

PubChem Compound

57363

PubChem Substance

46507645

ChemSpider

51714

BindingDB

50334788

RxNav

25025

ChEBI

5062

ChEMBL

CHEMBL710

ZINC

ZINC000003782599

Therapeutic Targets Database

DAP000045

PharmGKB

PA449627

PDBe Ligand

FIT

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Finasteride

MSDS

Clinical Trials

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View Sample Data

Manufacturers

Not Available

Packagers

• Accord Healthcare
• Actavis Group
• Advanced Pharmaceutical Services Inc.
• Amerisource Health Services Corp.
• AQ Pharmaceuticals Inc.
• A-S Medication Solutions LLC
• Atlantic Biologicals Corporation
• Aurobindo Pharma Ltd.
• Barr Pharmaceuticals
• Cardinal Health
• Chemical Works Of Gedeon Richter Ltd.
• Cipla Ltd.
• Diversified Healthcare Services Inc.
• Doctor Reddys Laboratories Ltd.
• Greenstone LLC
• Intas Pharmaceuticals Ltd.
• Kansas City Vaccine Co.
• Merck & Co.
• Murfreesboro Pharmaceutical Nursing Supply
• Mylan
• Northstar Rx LLC
• Nucare Pharmaceuticals Inc.
• PD-Rx Pharmaceuticals Inc.
• Physicians Total Care Inc.
• Prepackage Specialists
• Resource Optimization and Innovation LLC
• Southwood Pharmaceuticals
• Teva Pharmaceutical Industries Ltd.
• UDL Laboratories

Dosage Forms

Prices

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US6046183	No	2000-04-04	2011-03-20
CA2173457	No	1999-03-23	2014-10-11
CA1331601	No	1994-08-23	2011-08-23
US5942519	No	1999-08-24	2018-10-23

State

Solid

Experimental Properties

Predicted Properties

Predicted ADMET Features

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Mass Spec (NIST)

Not Available

Spectra

Chromatographic Properties

Collision Cross Sections (CCS)

Targets

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Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General 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.

Specific Function

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

Gene Name

SRD5A2

Uniprot ID

P31213

Uniprot Name

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

Molecular Weight

28407.035 Da

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. [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. 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. [Article]
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. [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. Joseph MA, Jayaseelan E, Ganapathi B, Stephen J: Hidradenitis suppurativa treated with finasteride. J Dermatolog Treat. 2005 Apr;16(2):75-8. [Article]
8. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General Function

Plays a key role in early steps of protein N-linked glycosylation by being required for the conversion of polyprenol into dolichol (PubMed:20637498). Dolichols are required for the synthesis of dolichol-linked monosaccharides and the oligosaccharide precursor used for N-glycosylation (PubMed:20637498). Acts as a polyprenol reductase that promotes the reduction of the alpha-isoprene unit of polyprenols into dolichols in a NADP-dependent mechanism (PubMed:20637498). Also able to convert testosterone (T) into 5-alpha-dihydrotestosterone (DHT) (PubMed:17986282, PubMed:26855069).

Specific Function

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

Gene Name

SRD5A3

Uniprot ID

Q9H8P0

Uniprot Name

Polyprenol reductase

Molecular Weight

36521.005 Da

References

1. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Yes

Actions

Inhibitor

General 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.

Specific Function

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

Gene Name

SRD5A1

Uniprot ID

P18405

Uniprot Name

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

Molecular Weight

29458.18 Da

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. [Article]
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. [Article]
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. [Article]
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. [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. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Inhibitor

General Function

Catalyzes the stereospecific NADPH-dependent reduction of the C4-C5 double bond of bile acid intermediates and steroid hormones carrying a delta(4)-3-one structure to yield an A/B cis-ring junction. This cis-configuration is crucial for bile acid biosynthesis and plays important roles in steroid metabolism. Capable of reducing a broad range of delta-(4)-3-ketosteroids from C18 (such as, 17beta-hydroxyestr-4-en-3-one) to C27 (such as, 7alpha-hydroxycholest-4-en-3-one).

Specific Function

aldo-keto reductase (NADPH) activity

Gene Name

AKR1D1

Uniprot ID

P51857

Uniprot Name

Aldo-keto reductase family 1 member D1

Molecular Weight

37376.615 Da

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. doi: 10.1074/jbc.C109.016931. Epub 2009 Jun 10. [Article]

Enzymes

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Substrate

General Function

A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981).

Specific Function

1,8-cineole 2-exo-monooxygenase activity

Gene Name

CYP3A4

Uniprot ID

P08684

Uniprot Name

Cytochrome P450 3A4

Molecular Weight

57342.67 Da

References

1. 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. [Article]
2. Hulin-Curtis SL, Petit D, Figg WD, Hsing AW, Reichardt JK: Finasteride metabolism and pharmacogenetics: new approaches to personalized prevention of prostate cancer. Future Oncol. 2010 Dec;6(12):1897-913. doi: 10.2217/fon.10.149. [Article]
3. Flockhart Table of Drug Interactions [Link]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Substrate

General Function

A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:10681376, PubMed:11093772, PubMed:12865317, PubMed:2732228). Exhibits high catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes 6beta-hydroxylation of the steroid hormones testosterone, progesterone, and androstenedione (PubMed:2732228). Catalyzes the oxidative conversion of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics, including calcium channel blocking drug nifedipine and immunosuppressive drug cyclosporine (PubMed:2732228).

Specific Function

aromatase activity

Gene Name

CYP3A5

Uniprot ID

P20815

Uniprot Name

Cytochrome P450 3A5

Molecular Weight

57108.065 Da

References

1. Flockhart Table of Drug Interactions [Link]

Kind

Protein

Organism

Humans

Pharmacological action

Unknown

Actions

Substrate

General Function

A cytochrome P450 monooxygenase involved in the metabolism of steroid hormones and vitamins during embryogenesis (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:11093772, PubMed:12865317, PubMed:14559847, PubMed:17178770, PubMed:9555064). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes 3beta-hydroxyandrost-5-en-17-one (dehydroepiandrosterone, DHEA), a precursor in the biosynthesis of androgen and estrogen steroid hormones (PubMed:17178770, PubMed:9555064). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1), particularly D-ring hydroxylated estrone at the C16-alpha position (PubMed:12865317, PubMed:14559847). Mainly hydroxylates all trans-retinoic acid (atRA) to 4-hydroxyretinoate and may play a role in atRA clearance during fetal development (PubMed:11093772). Also involved in the oxidative metabolism of xenobiotics including anticonvulsants (PubMed:9555064).

Specific Function

all-trans retinoic acid 18-hydroxylase activity

Gene Name

CYP3A7

Uniprot ID

P24462

Uniprot Name

Cytochrome P450 3A7

Molecular Weight

57469.95 Da

References

1. Flockhart Table of Drug Interactions [Link]

Transporters

Kind

Protein

Organism

Mouse

Pharmacological action

Unknown

Actions

Modulator

General Function

Mediates electroneutral potassium-chloride cotransport in mature neurons and is required for neuronal Cl(-) homeostasis (By similarity). As major extruder of intracellular chloride, it establishes the low neuronal Cl(-) levels required for chloride influx after binding of GABA-A and glycine to their receptors, with subsequent hyperpolarization and neuronal inhibition (By similarity). Involved in the regulation of dendritic spine formation and maturation (By similarity).

Specific Function

ammonium transmembrane transporter activity

Gene Name

Slc12a5

Uniprot ID

Q91V14

Uniprot Name

Solute carrier family 12 member 5

Molecular Weight

126269.555 Da

References

1. Modol L, Casas C, Llido A, Navarro X, Pallares M, Darbra S: Neonatal allopregnanolone or finasteride administration modifies hippocampal K(+) Cl(-) co-transporter expression during early development in male rats. J Steroid Biochem Mol Biol. 2014 Sep;143:343-7. doi: 10.1016/j.jsbmb.2014.05.002. Epub 2014 May 23. [Article]

Drug created at June 13, 2005 13:24 / Updated at September 29, 2024 12:43