Androstenedione

Identification

Generic Name
Androstenedione
DrugBank Accession Number
DB01536
Background

A delta-4 C19 steroid that is produced not only in the testis, but also in the ovary and the adrenal cortex. Depending on the tissue type, androstenedione can serve as a precursor to testosterone as well as estrone and estradiol.

Type
Small Molecule
Groups
Experimental, Illicit
Structure
Weight
Average: 286.4085
Monoisotopic: 286.193280076
Chemical Formula
C19H26O2
Synonyms
  • 4-Androstene-3,17-dione
  • 4-Androstenedione
  • Androst-4-ene-3,17-dione
  • Androstenedione
  • delta-4-Androstenedione
External IDs
  • SKF 2170

Pharmacology

Indication

Not Available

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Used in combination to manageHormone deficiencyCombination Product in combination with: Estrone (DB00655), Pregnenolone (DB02789), Testosterone (DB00624), Thyroid, porcine (DB09100), Androstenedione (DB01536), Androstenediol (DB01524)••••••••••••••••••
Used in combination to manageOvarian function insufficiencyCombination Product in combination with: Testosterone (DB00624), Estrone (DB00655), Thyroid, porcine (DB09100), Androstenediol (DB01524), Androstenedione (DB01536), Pregnenolone (DB02789)••••••••••••••••••
Used in combination to manageOvarian atrophyCombination Product in combination with: Pregnenolone (DB02789), Estrone (DB00655), Thyroid, porcine (DB09100), Androstenediol (DB01524), Testosterone (DB00624), Androstenedione (DB01536)••••••••••••••••••
Used in combination to manageHypoestrogenismCombination Product in combination with: Androstenedione (DB01536), Testosterone (DB00624), Androstenediol (DB01524), Thyroid, porcine (DB09100), Estrone (DB00655), Pregnenolone (DB02789)••••••••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

4-androstenedione is a 19-carbon steroid hormone produced in the adrenal glands and the gonads as an intermediate step in the biochemical pathway that produces the androgen testosterone and the estrogens estrone and estradiol.

TargetActionsOrganism
AAromatase
inhibitor
Humans
A17-beta-hydroxysteroid dehydrogenase type 1
inducer
Humans
A3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1
positive allosteric modulator
Humans
AAldo-keto reductase family 1 member C3
substrate
inducer
Humans
U6-deoxyerythronolide B hydroxylase
inducer
Saccharopolyspora erythraea (strain NRRL 23338)
Absorption

Not Available

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hover over products below to view reaction partners

Route of elimination

Not Available

Half-life

Not Available

Clearance

Not Available

Adverse Effects
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Toxicity

Not Available

Pathways
PathwayCategory
17-beta Hydroxysteroid Dehydrogenase III DeficiencyDisease
Androstenedione MetabolismMetabolic
Androgen and Estrogen MetabolismMetabolic
Aromatase DeficiencyDisease
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
AbametapirThe serum concentration of Androstenedione can be increased when it is combined with Abametapir.
AmiodaroneThe metabolism of Androstenedione can be decreased when combined with Amiodarone.
AmprenavirThe metabolism of Androstenedione can be decreased when combined with Amprenavir.
ApalutamideThe serum concentration of Androstenedione can be decreased when it is combined with Apalutamide.
AprepitantThe metabolism of Androstenedione can be decreased when combined with Aprepitant.
Food Interactions
Not Available

Categories

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 delta-4-steroids / 17-oxosteroids / Delta-4-steroids / Cyclohexenones / Organic oxides / Hydrocarbon derivatives
Substituents
17-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / Aliphatic homopolycyclic compound / Androgen-skeleton / Carbonyl group / Cyclic ketone / Cyclohexenone / Delta-4-steroid / Hydrocarbon derivative
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
3-oxo Delta(4)-steroid, 17-oxo steroid, androstanoid (CHEBI:16422) / androstane, C19 steroids (androgens) and derivatives, Androstane and derivatives, Androgens (C00280) / C19 steroids (androgens) and derivatives (LMST02020007)
Affected organisms
Not Available

Chemical Identifiers

UNII
409J2J96VR
CAS number
63-05-8
InChI Key
AEMFNILZOJDQLW-QAGGRKNESA-N
InChI
InChI=1S/C19H26O2/c1-18-9-7-13(20)11-12(18)3-4-14-15-5-6-17(21)19(15,2)10-8-16(14)18/h11,14-16H,3-10H2,1-2H3/t14-,15-,16-,18-,19-/m0/s1
IUPAC Name
(3aS,3bR,9aR,9bS,11aS)-9a,11a-dimethyl-1H,2H,3H,3aH,3bH,4H,5H,7H,8H,9H,9aH,9bH,10H,11H,11aH-cyclopenta[a]phenanthrene-1,7-dione
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CCC2=CC(=O)CC[C@]12C

References

Synthesis Reference

Angela M. H. Brodie, Harry J. Brodie, David A. Marsh, "Ester derivatives of 4-hydroxy-4-androstene-3,17-dione and a method for inhibiting estrogen biosynthesis." U.S. Patent US4235893, issued October, 1962.

US4235893
General References
Not Available
Human Metabolome Database
HMDB0000053
KEGG Drug
D00051
KEGG Compound
C00280
PubChem Compound
6128
PubChem Substance
46508011
ChemSpider
5898
BindingDB
91713
RxNav
784
ChEBI
16422
ChEMBL
CHEMBL274826
ZINC
ZINC000004428526
PDBe Ligand
ASD
Wikipedia
Androstenedione
PDB Entries
1eup / 1qyx / 1xf0 / 2vct / 2vcv / 3cas / 3eqm / 3iw1 / 3nbr / 3nhx
show 18 more

Clinical Trials

Clinical Trials
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Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package
PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
2CompletedTreatmentEstrogen Receptor and/or Progesterone Receptor Positive / HER2 negative / Stage IV Breast Cancer AJCC v6 and v71somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage Forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)158 °CPhysProp
water solubility57.8 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP2.75HANSCH,C ET AL. (1995)
logS-3.69ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.027 mg/mLALOGPS
logP2.93ALOGPS
logP3.93Chemaxon
logS-4ALOGPS
pKa (Strongest Acidic)18.52Chemaxon
pKa (Strongest Basic)-4.8Chemaxon
Physiological Charge0Chemaxon
Hydrogen Acceptor Count2Chemaxon
Hydrogen Donor Count0Chemaxon
Polar Surface Area34.14 Å2Chemaxon
Rotatable Bond Count0Chemaxon
Refractivity83.61 m3·mol-1Chemaxon
Polarizability33.21 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9793
Caco-2 permeable+0.8011
P-glycoprotein substrateSubstrate0.5526
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IINon-inhibitor0.6615
Renal organic cation transporterNon-inhibitor0.6632
CYP450 2C9 substrateNon-substrate0.8548
CYP450 2D6 substrateNon-substrate0.9131
CYP450 3A4 substrateSubstrate0.7193
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9387
CYP450 2D6 inhibitorNon-inhibitor0.9386
CYP450 2C19 inhibitorNon-inhibitor0.8138
CYP450 3A4 inhibitorNon-inhibitor0.8483
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8067
Ames testNon AMES toxic0.9508
CarcinogenicityNon-carcinogens0.9313
BiodegradationNot ready biodegradable0.9343
Rat acute toxicity1.5360 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7599
hERG inhibition (predictor II)Non-inhibitor0.7469
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Download (11.2 KB)
Spectra
SpectrumSpectrum TypeSplash Key
GC-MS Spectrum - GC-MSGC-MSsplash10-004l-5910000000-518e1ad38bcc73325b53
GC-MS Spectrum - GC-MSGC-MSsplash10-004l-5910000000-5172e05f9889ee2bfaf4
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-0590000000-502d6b821317a01a1990
GC-MS Spectrum - EI-BGC-MSsplash10-000f-8940000000-f2892fe3b281d44164c8
GC-MS Spectrum - EI-BGC-MSsplash10-007d-1960000000-167f1765b095da9d603b
GC-MS Spectrum - GC-MSGC-MSsplash10-004l-5910000000-518e1ad38bcc73325b53
GC-MS Spectrum - GC-MSGC-MSsplash10-004l-5910000000-5172e05f9889ee2bfaf4
Mass Spectrum (Electron Ionization)MSsplash10-059m-3940000000-9cb32ac21e46afb2829a
MS/MS Spectrum - Quattro_QQQ 10V, PositiveLC-MS/MSsplash10-000i-0090000000-36e848ba16b141eef47b
MS/MS Spectrum - Quattro_QQQ 25V, PositiveLC-MS/MSsplash10-052b-9600000000-712954fc35a84c8217de
MS/MS Spectrum - Quattro_QQQ 40V, PositiveLC-MS/MSsplash10-052b-9300000000-f8e9aa16b4b208b69f7b
MS/MS Spectrum - EI-B (HITACHI M-80) , PositiveLC-MS/MSsplash10-000f-8940000000-e12025ea2b7808c64b9c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-052b-6910000000-b616785c86a92f46158e
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-052b-9800000000-73e545a1eb2232d55371
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00kb-5790000000-735473bc44dd70e29259
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-00kb-5790000000-114675a4457063901f2b
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-00kr-0190000000-cb415566097f2a80e5e8
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-3c35cfabb8fb0492a166
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-01b9-1950000000-72bcdcaaed06bc1b5f5c
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-000i-0090000000-aa7218b5a955c34f0b68
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0gbl-0090000000-78b5142964aaa61bcb76
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0729-0900000000-2789dadf184fc699ffdf
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-176.5431327
predicted
DarkChem Lite v0.1.0
[M-H]-176.2939327
predicted
DarkChem Lite v0.1.0
[M-H]-176.7669327
predicted
DarkChem Lite v0.1.0
[M-H]-176.5377327
predicted
DarkChem Lite v0.1.0
[M-H]-176.3020327
predicted
DarkChem Lite v0.1.0
[M-H]-169.07628
predicted
DeepCCS 1.0 (2019)
[M+H]+176.9598327
predicted
DarkChem Lite v0.1.0
[M+H]+167.4900336
predicted
DarkChem Standard v0.1.0
[M+H]+177.4454327
predicted
DarkChem Lite v0.1.0
[M+H]+177.2297327
predicted
DarkChem Lite v0.1.0
[M+H]+177.1565327
predicted
DarkChem Lite v0.1.0
[M+H]+171.34334
predicted
DeepCCS 1.0 (2019)
[M+Na]+177.1647327
predicted
DarkChem Lite v0.1.0
[M+Na]+187.5575738
predicted
DarkChem Standard v0.1.0
[M+Na]+176.9993327
predicted
DarkChem Lite v0.1.0
[M+Na]+176.9557327
predicted
DarkChem Lite v0.1.0
[M+Na]+177.56035
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
A cytochrome P450 monooxygenase that catalyzes the conversion of C19 androgens, androst-4-ene-3,17-dione (androstenedione) and testosterone to the C18 estrogens, estrone and estradiol, respectively (PubMed:27702664, PubMed:2848247). Catalyzes three successive oxidations of C19 androgens: two conventional oxidations at C19 yielding 19-hydroxy and 19-oxo/19-aldehyde derivatives, followed by a third oxidative aromatization step that involves C1-beta hydrogen abstraction combined with cleavage of the C10-C19 bond to yield a phenolic A ring and formic acid (PubMed:20385561). Alternatively, the third oxidative reaction yields a 19-norsteroid and formic acid. Converts dihydrotestosterone to delta1,10-dehydro 19-nordihydrotestosterone and may play a role in homeostasis of this potent androgen (PubMed:22773874). Also displays 2-hydroxylase activity toward estrone (PubMed:22773874). 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 (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20385561, PubMed:22773874)
Specific Function
aromatase activity
Gene Name
CYP19A1
Uniprot ID
P11511
Uniprot Name
Aromatase
Molecular Weight
57882.48 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
Inducer
General Function
Favors the reduction of estrogens and androgens. Converts estrone (E1) to a more potent estrogen, 17beta-estradiol (E2) (PubMed:8994190). Also has 20-alpha-HSD activity. Uses preferentially NADH
Specific Function
17-beta-hydroxysteroid dehydrogenase (NADP+) activity
Gene Name
HSD17B1
Uniprot ID
P14061
Uniprot Name
17-beta-hydroxysteroid dehydrogenase type 1
Molecular Weight
34949.715 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Positive allosteric modulator
General Function
A bifunctional enzyme responsible for the oxidation and isomerization of 3beta-hydroxy-Delta(5)-steroid precursors to 3-oxo-Delta(4)-steroids, an essential step in steroid hormone biosynthesis. Specifically catalyzes the conversion of pregnenolone to progesterone, 17alpha-hydroxypregnenolone to 17alpha-hydroxyprogesterone, dehydroepiandrosterone (DHEA) to 4-androstenedione, and androstenediol to testosterone. Additionally, catalyzes the interconversion between 3beta-hydroxy and 3-oxo-5alpha-androstane steroids controlling the bioavalability of the active forms. Specifically converts dihydrotestosterone to its inactive form 5alpha-androstanediol, that does not bind androgen receptor/AR. Also converts androstanedione, a precursor of testosterone and estrone, to epiandrosterone (PubMed:1401999, PubMed:2139411). Expected to use NAD(+) as preferred electron donor for the 3beta-hydroxy-steroid dehydrogenase activity and NADPH for the 3-ketosteroid reductase activity (Probable)
Specific Function
3-beta-hydroxy-delta5-steroid dehydrogenase (NAD+) activity
Gene Name
HSD3B1
Uniprot ID
P14060
Uniprot Name
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 1
Molecular Weight
42251.25 Da
References
  1. Ishii-Ohba H, Inano H, Tamaoki B: Purification and properties of testicular 3 beta-hydroxy-5-ene-steroid dehydrogenase and 5-ene-4-ene isomerase. J Steroid Biochem. 1986 Oct;25(4):555-60. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Substrate
Inducer
General Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone (PubMed:10622721, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:9927279). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:11165022, PubMed:14672942). Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol (PubMed:10622721, PubMed:10998348, PubMed:11165022, PubMed:15047184, PubMed:19010934, PubMed:20036328). Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:10557352, PubMed:10998348, PubMed:11165022, PubMed:14672942, PubMed:7650035, PubMed:9415401). Also displays retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338)
Specific Function
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]
  3. Adeniji A, Uddin MJ, Zang T, Tamae D, Wangtrakuldee P, Marnett LJ, Penning TM: Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor. J Med Chem. 2016 Aug 25;59(16):7431-44. doi: 10.1021/acs.jmedchem.6b00160. Epub 2016 Aug 12. [Article]
Kind
Protein
Organism
Saccharopolyspora erythraea (strain NRRL 23338)
Pharmacological action
Unknown
Actions
Inducer
General Function
Catalyzes the conversion of 6-deoxyerythronolide B (6-DEB) to erythronolide B (EB) by the insertion of an oxygen at the 6S position of 6-DEB. Requires the participation of a ferredoxin and a ferredoxin reductase for the transfer of electrons from NADPH to the monooxygenase.
Specific Function
cholest-4-en-3-one 26-monooxygenase activity
Gene Name
eryF
Uniprot ID
Q00441
Uniprot Name
6-deoxyerythronolide B hydroxylase
Molecular Weight
45098.685 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
No
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. Sevrioukova IF, Poulos TL: Structure and mechanism of the complex between cytochrome P4503A4 and ritonavir. Proc Natl Acad Sci U S A. 2010 Oct 26;107(43):18422-7. doi: 10.1073/pnas.1010693107. Epub 2010 Oct 11. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Cytosolic aldo-keto reductase that catalyzes the NADH and NADPH-dependent reduction of ketosteroids to hydroxysteroids. Acts as a NAD(P)(H)-dependent 3-, 17- and 20-ketosteroid reductase on the steroid nucleus and side chain and regulates the metabolism of androgens, estrogens and progesterone (PubMed:10622721, PubMed:11165022, PubMed:7650035, PubMed:9415401, PubMed:9927279). Displays the ability to catalyze both oxidation and reduction in vitro, but most probably acts as a reductase in vivo since the oxidase activity measured in vitro is inhibited by physiological concentration of NADPH (PubMed:11165022, PubMed:14672942). Acts preferentially as a 17-ketosteroid reductase and has the highest catalytic efficiency of the AKR1C enzyme for the reduction of delta4-androstenedione to form testosterone (PubMed:20036328). Reduces prostaglandin (PG) D2 to 11beta-prostaglandin F2, progesterone to 20alpha-hydroxyprogesterone and estrone to 17beta-estradiol (PubMed:10622721, PubMed:10998348, PubMed:11165022, PubMed:15047184, PubMed:19010934, PubMed:20036328). Catalyzes the transformation of the potent androgen dihydrotestosterone (DHT) into the less active form, 5-alpha-androstan-3-alpha,17-beta-diol (3-alpha-diol) (PubMed:10557352, PubMed:10998348, PubMed:11165022, PubMed:14672942, PubMed:7650035, PubMed:9415401). Also displays retinaldehyde reductase activity toward 9-cis-retinal (PubMed:21851338)
Specific Function
15-hydroxyprostaglandin-D dehydrogenase (NADP+) activity
Gene Name
AKR1C3
Uniprot ID
P42330
Uniprot Name
Aldo-keto reductase family 1 member C3
Molecular Weight
36852.89 Da
References
  1. Adeniji A, Uddin MJ, Zang T, Tamae D, Wangtrakuldee P, Marnett LJ, Penning TM: Discovery of (R)-2-(6-Methoxynaphthalen-2-yl)butanoic Acid as a Potent and Selective Aldo-keto Reductase 1C3 Inhibitor. J Med Chem. 2016 Aug 25;59(16):7431-44. doi: 10.1021/acs.jmedchem.6b00160. Epub 2016 Aug 12. [Article]

Drug created at June 13, 2005 13:24 / Updated at August 26, 2024 19:22