Identification

Name
Prasterone
Accession Number
DB01708  (EXPT00519, DB06593)
Type
Small Molecule
Groups
Approved, Investigational, Nutraceutical
Description

Prasterone, also known as dehydroepiandrosterone (DHEA) is a major C19 steroid produced by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (DHEA) can be converted to testosterone; androstenedione; estradiol; and estrone. Most of DHEA is sulfated (dehydroepiandrosterone sulfate) before secretion.

In the United States, DHEA or DHEAS have been advertised with claims that they may be beneficial for a wide variety of ailments. DHEA and DHEAS are readily available in the United States, where they are marketed as over-the-counter dietary supplements. In November 2016, DHEA was approved (as Intrarosa) to treat women experiencing moderate to severe pain during sexual intercourse (dyspareunia), a symptom of vulvar and vaginal atrophy (VVA), due to menopause.

In Canada, a prescription is required to buy DHEA.

Structure
Thumb
Synonyms
  • 3-beta-hydroxy-5-androsten-17-one
  • 3beta-hydroxyandrost-5-en-17-one
  • 3β-hydroxyandrost-5-en-17-one
  • Dehydroandrosterone
  • Dehydroepiandrosterone
  • Dehydroisoandrosterone
  • DHEA
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
IntrarosaInsert6.5 mg/1VaginalEndoceutics Inc.2017-07-192017-07-19Us
IntrarosaInsert6.5 mg/1VaginalAmag Pharmaceuticals Inc2017-06-06Not applicableUs
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
PrasteraPrasterone (200 mg/1) + Ibuprofen (400 mg/1)KitOralHealth Science Funding, Llc2014-04-04Not applicableUs
International/Other Brands
Biolaif / Fidelin (Paladin) / OVIGYN-D (Alembic Pharmaceuicals Ltd)
Categories
UNII
459AG36T1B
CAS number
53-43-0
Weight
Average: 288.4244
Monoisotopic: 288.20893014
Chemical Formula
C19H28O2
InChI Key
FMGSKLZLMKYGDP-USOAJAOKSA-N
InChI
InChI=1S/C19H28O2/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/h3,13-16,20H,4-11H2,1-2H3/t13-,14-,15-,16-,18-,19-/m0/s1
IUPAC Name
(1S,2R,5S,10R,11S,15S)-5-hydroxy-2,15-dimethyltetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-7-en-14-one
SMILES
[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]1([H])[C@@]2([H])CC=C2C[C@@]([H])(O)CC[C@]12C

Pharmacology

Indication

DHEA is taken as a supplement for a variety of unsubstantiated indications. The following indications have shown promise and are backed up by some scientific evidence: schizophrenia (DHEA may be more effective in women than men); improving the appearance of older people’s skin (taking DHEA by mouth seems to increase skin thickness and moisture, and decrease facial “age spots” in elderly men and women); improving ability to achieve an erection in men with sexual dysfunction. Additionally, DHEA has shown promise in improving symptoms of lupus (SLE). Taking DHEA by mouth along with conventional treatment may help reduce the number of times symptoms flare up and may allow a reduction in the dose of prescription drugs needed. DHEA may also help SLE symptoms such as muscle ache and mouth ulcers. DHEA also seems to strengthen bones in SLE patients being treated with high-dose steroids (corticosteroids). DHEA also shows promise in the treatment of osteoporosis. Taking DHEA by mouth daily seems to improve bone mineral density (BMD) in older women and men with osteoporosis or osteopenia (pre-osteoporosis). DHEA may also increase BMD in young women with the eating disorder called anorexia nervosa. DHEA is often prescribed in India for the induction of ovulation to improve chances of pregnancy.

Pharmacodynamics

DHEA is naturally produced from cholesterol through two cytochrome P450 enzymes. Cholesterol is converted to pregnenolone by the enzyme P450 scc (side chain cleavage); then another enzyme, CYP17A1, converts pregnenolone to 17α-Hydroxypregnenolone and then to DHEA. Regular exercise is known to increase DHEA production in the body. Calorie restriction has also been shown to increase DHEA in primates. Some theorize that the increase in endogenous DHEA brought about by calorie restriction is partially responsible for the longer life expectancy known to be associated with calorie restriction.

Mechanism of action

DHEA can be understood as a prohormone for the sex steroids. DHEAS may be viewed as buffer and reservoir. As most DHEA is produced by the zona reticularis of the adrenal cortex, it is argued that there is a role in the immune and stress response. As almost all DHEA is derived from the adrenal glands, blood measurements of DHEAS/DHEA are useful to detect excess adrenal activity as seen in adrenal cancer or hyperplasia, including certain forms of congenital adrenal hyperplasia. Women with polycystic ovary syndrome tend to have elevated levels of DHEAS.

TargetActionsOrganism
UEstrogen receptor alpha
binder
Human
UEstrogen receptor beta
activator
Human
UGABA-A receptor (anion channel)
antagonist
Human
UNMDA receptor
agonist
Human
UAndrogen receptor
agonist
Human
UEstradiol 17-beta-dehydrogenase 1Not AvailableHuman
UBile salt sulfotransferaseNot AvailableHuman
USulfotransferase family cytosolic 2B member 1Not AvailableHuman
UPeroxisome proliferator-activated receptor alpha
activator
Human
USigma non-opioid intracellular receptor 1
agonist
Human
UNuclear receptor subfamily 1 group I member 2
activator
Human
UNuclear receptor subfamily 1 group I member 3
activator
Human
USteroid Delta-isomeraseNot AvailablePseudomonas putida
UCholesterol oxidaseNot AvailableBrevibacterium sterolicum
Absorption

Following a 50-mg DHEA PO dose in cynomolgus monkeys, systemic availability was only 3.1 +/- 0.4%. [PMID: 12970301]

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic. As shown by their high conversion ratios (in a study involving cynomolgus monkeys), the major circulating metabolites of DHEA are DHEA-S, androsterone glucuronide, and androstane-3 alpha,17 beta-diol-glucuronide. [PMID: 12970301]

Route of elimination
Not Available
Half life

12 hours

Clearance
Not Available
Toxicity

Acute oral toxicity (LD50): >10000 mg/kg [Rat]. Lowest Published Toxic Dose (TDL) [Man] - Route: Oral; Dose: 10 mg/kg/2W intermittent.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(1,2,6,7-3H)TestosteroneThe serum concentration of (1,2,6,7-3H)Testosterone can be increased when it is combined with Prasterone.
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Prasterone.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Prasterone.
1-TestosteroneThe serum concentration of 1-Testosterone can be increased when it is combined with Prasterone.
18-methyl-19-nortestosteroneThe serum concentration of 18-methyl-19-nortestosterone can be increased when it is combined with Prasterone.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Prasterone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Prasterone.
4-HydroxytestosteroneThe serum concentration of 4-Hydroxytestosterone can be increased when it is combined with Prasterone.
5-androstenedioneThe metabolism of Prasterone can be decreased when combined with 5-androstenedione.
5beta-dihydrotestosteroneThe serum concentration of 5beta-dihydrotestosterone can be increased when it is combined with Prasterone.
Food Interactions
Not Available

References

Synthesis Reference

Isao Sugimoto, Yoko Sawase, "Stable preparation of water-soluble salts of dehydroepiandrosterone sulfate for parenteral administration." U.S. Patent US4061744, issued January, 1977.

US4061744
General References
  1. Baker WL, Karan S, Kenny AM: Effect of dehydroepiandrosterone on muscle strength and physical function in older adults: a systematic review. J Am Geriatr Soc. 2011 Jun;59(6):997-1002. doi: 10.1111/j.1532-5415.2011.03410.x. Epub 2011 Jun 7. [PubMed:21649617]
  2. Alkatib AA, Cosma M, Elamin MB, Erickson D, Swiglo BA, Erwin PJ, Montori VM: A systematic review and meta-analysis of randomized placebo-controlled trials of DHEA treatment effects on quality of life in women with adrenal insufficiency. J Clin Endocrinol Metab. 2009 Oct;94(10):3676-81. doi: 10.1210/jc.2009-0672. Epub 2009 Sep 22. [PubMed:19773400]
  3. Arlt W: Dehydroepiandrosterone and ageing. Best Pract Res Clin Endocrinol Metab. 2004 Sep;18(3):363-80. [PubMed:15261843]
  4. Wallace MB, Lim J, Cutler A, Bucci L: Effects of dehydroepiandrosterone vs androstenedione supplementation in men. Med Sci Sports Exerc. 1999 Dec;31(12):1788-92. [PubMed:10613429]
  5. Grimley Evans J, Malouf R, Huppert F, van Niekerk JK: Dehydroepiandrosterone (DHEA) supplementation for cognitive function in healthy elderly people. Cochrane Database Syst Rev. 2006 Oct 18;(4):CD006221. [PubMed:17054283]
  6. Fuller SJ, Tan RS, Martins RN: Androgens in the etiology of Alzheimer's disease in aging men and possible therapeutic interventions. J Alzheimers Dis. 2007 Sep;12(2):129-42. [PubMed:17917157]
  7. Thijs L, Fagard R, Forette F, Nawrot T, Staessen JA: Are low dehydroepiandrosterone sulphate levels predictive for cardiovascular diseases? A review of prospective and retrospective studies. Acta Cardiol. 2003 Oct;58(5):403-10. [PubMed:14609305]
  8. Barrett-Connor E, Khaw KT, Yen SS: A prospective study of dehydroepiandrosterone sulfate, mortality, and cardiovascular disease. N Engl J Med. 1986 Dec 11;315(24):1519-24. [PubMed:2946952]
  9. Arnlov J, Pencina MJ, Amin S, Nam BH, Benjamin EJ, Murabito JM, Wang TJ, Knapp PE, D'Agostino RB Sr, Bhasin S, Vasan RS: Endogenous sex hormones and cardiovascular disease incidence in men. Ann Intern Med. 2006 Aug 1;145(3):176-84. [PubMed:16880459]
  10. Crosbie D, Black C, McIntyre L, Royle PL, Thomas S: Dehydroepiandrosterone for systemic lupus erythematosus. Cochrane Database Syst Rev. 2007 Oct 17;(4):CD005114. [PubMed:17943841]
  11. Mattison JA, Lane MA, Roth GS, Ingram DK: Calorie restriction in rhesus monkeys. Exp Gerontol. 2003 Jan-Feb;38(1-2):35-46. [PubMed:12543259]
  12. Roberts E: The importance of being dehydroepiandrosterone sulfate (in the blood of primates): a longer and healthier life? Biochem Pharmacol. 1999 Feb 15;57(4):329-46. [PubMed:9933021]
  13. Leblanc M, Labrie C, Belanger A, Candas B, Labrie F: Bioavailability and pharmacokinetics of dehydroepiandrosterone in the cynomolgus monkey. J Clin Endocrinol Metab. 2003 Sep;88(9):4293-302. [PubMed:12970301]
  14. Casson PR, Lindsay MS, Pisarska MD, Carson SA, Buster JE: Dehydroepiandrosterone supplementation augments ovarian stimulation in poor responders: a case series. Hum Reprod. 2000 Oct;15(10):2129-32. [PubMed:11006185]
  15. Chang DM, Lan JL, Lin HY, Luo SF: Dehydroepiandrosterone treatment of women with mild-to-moderate systemic lupus erythematosus: a multicenter randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2002 Nov;46(11):2924-7. [PubMed:12428233]
  16. The NIH National Library of Medicine [Link]
External Links
Human Metabolome Database
HMDB0000077
KEGG Drug
D08409
KEGG Compound
C01227
PubChem Compound
5881
PubChem Substance
46508824
ChemSpider
5670
BindingDB
50223368
ChEBI
28689
ChEMBL
CHEMBL90593
Therapeutic Targets Database
DNC001146
PharmGKB
PA451993
IUPHAR
2370
Guide to Pharmacology
GtP Drug Page
HET
AND
Wikipedia
Dehydroepiandrosterone
ATC Codes
A14AA07 — PrasteroneG03EA03 — Prasterone and estrogen
PDB Entries
1coy / 1e3r / 1j99 / 1q22 / 3dhe
MSDS
Download (19.8 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0Active Not RecruitingSupportive CareCognitive Dysfunctions1
0RecruitingOtherDiabetes, Diabetes Mellitus Type 12
0WithdrawnTreatmentPremature Ovarian Failure (POF)1
1CompletedOtherParkinson's Disease (PD)1
1CompletedTreatmentIrregular Menses1
1CompletedTreatmentVulvovaginal Atrophy1
1RecruitingSupportive CareHealthy Women / Women With Ovarian Reserve Diminish1
1TerminatedTreatmentCancer, Breast2
1, 2RecruitingTreatmentSynovial Sarcoma1
2CompletedPreventionMultiple Myeloma and Plasma Cell Neoplasm1
2CompletedTreatmentCrohn's Disease (CD)1
2CompletedTreatmentDepressive Disorders / Moods Disorders1
2CompletedTreatmentErectile Dysfunction (ED)1
2CompletedTreatmentGingival Inflammation / Inflammatory Reaction / Periodontitis1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentLacrimal Apparatus Diseases / Salivary Gland Diseases / Sjögren's Syndrome / Xerostomia1
2CompletedTreatmentLibido1
2CompletedTreatmentLupus Erythematosus, Systemic / Sjögren's Syndrome1
2CompletedTreatmentSystemic Lupus Erythematosus (SLE)1
2Not Yet RecruitingTreatmentPosttraumatic Stress Disorders1
2Not Yet RecruitingTreatmentPulmonary Arterial Hypertension (PAH)1
2TerminatedTreatmentAndrogen Receptor Gene Overexpression / Estrogen Receptor Negative Neoplasm / Estrogen Receptor Positive Breast Cancer / Metastatic Breastcancer / Progesterone Receptor Negative Neoplasm / Progesterone Receptor Positive Tumor1
2Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
2, 3CompletedTreatmentAbstinence Syndrome / Behavior, Addictive1
2, 3CompletedTreatmentAnorexia Nervosa (AN)1
2, 3CompletedTreatmentMenopausal Hot Flushes1
2, 3CompletedTreatmentSystemic Lupus Erythematosus (SLE)2
2, 3Unknown StatusTreatmentChanges in AMH / Diminished Ovarian Reserve (DOR) / Efficacy of DHEA / Pregnancy Rate1
3Active Not RecruitingSupportive CareCancer, Breast / Gynecologic Cancers1
3CompletedTreatmentAddison's Disease1
3CompletedTreatmentAdrenal Insufficiency1
3CompletedTreatmentAnorexia Nervosa (AN)1
3CompletedTreatmentArtificial Reproduction Technology / Dehydroepiandrosterone / DHEAS / Gene Expression of Cumulus Cells / Ovarian Hyper-stimulation Protocol1
3CompletedTreatmentDiminished Ovarian Reserve (DOR) / Infertilities / Ovarian Aging / Predicted Poor-responders1
3CompletedTreatmentHealthy Volunteers1
3CompletedTreatmentLibido Disorder / Menopausal Syndromes / Quality of Life1
3CompletedTreatmentMenopausal Hot Flushes / Vasomotor Symptoms1
3CompletedTreatmentPregnancy2
3CompletedTreatmentQuality of Life / Skin Aging1
3CompletedTreatmentSubfertility1
3CompletedTreatmentSystemic Lupus Erythematosus (SLE)2
3CompletedTreatmentVulvovaginal Atrophy5
3Not Yet RecruitingTreatmentHypoactive Sexual Desire Disorder (HSDD)1
3RecruitingPreventionPremature Births1
3RecruitingTreatmentHypoactive Sexual Desire Disorder (HSDD)1
3RecruitingTreatmentSubfertility2
3Unknown StatusPreventionLupus1
3Unknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD) / Pulmonary Hypertension (PH)1
4Active Not RecruitingTreatmentInfertilities1
4CompletedPreventionMacular Pigment Optical Density1
4CompletedTreatmentInfertilities1
4RecruitingTreatmentPainful Intercourse1
4RecruitingTreatmentSubfertility1
4Unknown StatusTreatmentSjögren's Syndrome1
Not AvailableActive Not RecruitingPreventionType 2 Diabetes Mellitus1
Not AvailableCompletedNot AvailableInfertilities1
Not AvailableCompletedPreventionAging / BMI >30 kg/m2 / Insulin Resistance1
Not AvailableCompletedPreventionHealthy Volunteers1
Not AvailableCompletedTreatmentAdrenal Insufficiency1
Not AvailableCompletedTreatmentAging1
Not AvailableCompletedTreatmentCancer Cachexia1
Not AvailableRecruitingTreatmentSubfertility1
Not AvailableUnknown StatusTreatmentHypoactive Sexual Desire Disorder (HSDD)1
Not AvailableWithdrawnTreatmentInfertilities1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
InsertVaginal6.5 mg/1
KitOral
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8268806No2011-03-192031-03-19Us
US8629129No2008-08-072028-08-07Us
US8957054No2008-08-072028-08-07Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)140-141 °CPhysProp
water solubility63.5 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP3.23HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0438 mg/mLALOGPS
logP3.53ALOGPS
logP3.36ChemAxon
logS-3.8ALOGPS
pKa (Strongest Acidic)18.2ChemAxon
pKa (Strongest Basic)-1.4ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count0ChemAxon
Refractivity84.66 m3·mol-1ChemAxon
Polarizability34.09 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+0.9611
Caco-2 permeable+0.8816
P-glycoprotein substrateSubstrate0.6176
P-glycoprotein inhibitor IInhibitor0.6272
P-glycoprotein inhibitor IINon-inhibitor0.9014
Renal organic cation transporterNon-inhibitor0.7596
CYP450 2C9 substrateNon-substrate0.8415
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.7404
CYP450 1A2 substrateNon-inhibitor0.9313
CYP450 2C9 inhibitorNon-inhibitor0.9672
CYP450 2D6 inhibitorNon-inhibitor0.9476
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8399
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9013
Ames testNon AMES toxic0.9382
CarcinogenicityNon-carcinogens0.947
BiodegradationNot ready biodegradable0.8998
Rat acute toxicity1.5214 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8861
hERG inhibition (predictor II)Non-inhibitor0.7176
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
GC-MS Spectrum - GC-MS (1 MEOX; 1 TMS)GC-MSsplash10-004i-4920000000-9dc14963a290268534b8
GC-MS Spectrum - GC-MS (1 TMS)GC-MSsplash10-004i-3910000000-2bbc760dbeb7f9f1ebfc
GC-MS Spectrum - EI-BGC-MSsplash10-0abi-1790000000-52f5e67bc4d1fab73561
Mass Spectrum (Electron Ionization)MSsplash10-0a4l-6940000000-948ad487c238d48aa9be
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0fk9-0190000000-66ac82624767dc6821e5
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0w90-1690000000-b3a231fc509b7a34e09c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-08gj-1930000000-309dc082cc36ec9dcd8c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-06sj-2910000000-378638f2a861c948f79d
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0536-3900000000-72e80e1a07c4d3a40a7a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0036-4900000000-26c8272483a80d1b5eab
MS/MS Spectrum - , positiveLC-MS/MSsplash10-000i-0290000000-1a3588ca5d5bacb9ad30
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0bta-3920000000-2df257db43df6cc86570
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

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-beta-hydroxysteroids / 3-beta-hydroxy delta-5-steroids / 17-oxosteroids / Delta-5-steroids / Secondary alcohols / Ketones / Cyclic alcohols and derivatives / Organic oxides / Hydrocarbon derivatives
Substituents
Androgen-skeleton / 3-hydroxy-delta-5-steroid / 3-hydroxysteroid / 3-beta-hydroxysteroid / 3-beta-hydroxy-delta-5-steroid / Oxosteroid / 17-oxosteroid / Hydroxysteroid / Delta-5-steroid / Cyclic alcohol
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
3beta-hydroxy steroid, 17-oxo steroid, androstanoid (CHEBI:28689) / C19 steroids (androgens) and derivatives, Androstane and derivatives, Androgens (C01227) / C19 steroids (androgens) and derivatives (LMST02020021)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissu...
Gene Name
ESR1
Uniprot ID
P03372
Uniprot Name
Estrogen receptor
Molecular Weight
66215.45 Da
References
  1. Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, Moreno CT, Schmidt A, Harada S, Freedman LP, Reszka AA: Direct agonist/antagonist functions of dehydroepiandrosterone. Endocrinology. 2005 Nov;146(11):4568-76. Epub 2005 Jun 30. [PubMed:15994348]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Nuclear hormone receptor. Binds estrogens with an affinity similar to that of ESR1, and activates expression of reporter genes containing estrogen response elements (ERE) in an estrogen-dependent m...
Gene Name
ESR2
Uniprot ID
Q92731
Uniprot Name
Estrogen receptor beta
Molecular Weight
59215.765 Da
References
  1. Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, Moreno CT, Schmidt A, Harada S, Freedman LP, Reszka AA: Direct agonist/antagonist functions of dehydroepiandrosterone. Endocrinology. 2005 Nov;146(11):4568-76. Epub 2005 Jun 30. [PubMed:15994348]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Antagonist
General Function
Inhibitory extracellular ligand-gated ion channel activity
Specific Function
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

Components:
References
  1. Sousa A, Ticku MK: Interactions of the neurosteroid dehydroepiandrosterone sulfate with the GABA(A) receptor complex reveals that it may act via the picrotoxin site. J Pharmacol Exp Ther. 1997 Aug;282(2):827-33. [PubMed:9262347]
Kind
Protein group
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Voltage-gated cation channel activity
Specific Function
NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic p...

Components:
References
  1. Compagnone NA, Mellon SH: Dehydroepiandrosterone: a potential signalling molecule for neocortical organization during development. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4678-83. [PubMed:9539798]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Steroid hormone receptors are ligand-activated transcription factors that regulate eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Transcription ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Chen F, Knecht K, Birzin E, Fisher J, Wilkinson H, Mojena M, Moreno CT, Schmidt A, Harada S, Freedman LP, Reszka AA: Direct agonist/antagonist functions of dehydroepiandrosterone. Endocrinology. 2005 Nov;146(11):4568-76. Epub 2005 Jun 30. [PubMed:15994348]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Testosterone dehydrogenase (nad+) activity
Specific Function
Favors the reduction of estrogens and androgens. Also has 20-alpha-HSD activity. Uses preferentially NADH.
Gene Name
HSD17B1
Uniprot ID
P14061
Uniprot Name
Estradiol 17-beta-dehydrogenase 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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfonation of steroids and bile acids in the liver and adrenal glands.
Gene Name
SULT2A1
Uniprot ID
Q06520
Uniprot Name
Bile salt sulfotransferase
Molecular Weight
33779.57 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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Steroid sulfotransferase activity
Specific Function
Sulfotransferase that utilizes 3'-phospho-5'-adenylyl sulfate (PAPS) as sulfonate donor to catalyze the sulfate conjugation of many hormones, neurotransmitters, drugs and xenobiotic compounds. Sulf...
Gene Name
SULT2B1
Uniprot ID
O00204
Uniprot Name
Sulfotransferase family cytosolic 2B member 1
Molecular Weight
41307.32 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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Kohalmy K, Tamasi V, Kobori L, Sarvary E, Pascussi JM, Porrogi P, Rozman D, Prough RA, Meyer UA, Monostory K: Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor. Drug Metab Dispos. 2007 Sep;35(9):1495-501. Epub 2007 Jun 25. [PubMed:17591676]
  2. Tamasi V, Miller KK, Ripp SL, Vila E, Geoghagen TE, Prough RA: Modulation of receptor phosphorylation contributes to activation of peroxisome proliferator activated receptor alpha by dehydroepiandrosterone and other peroxisome proliferators. Mol Pharmacol. 2008 Mar;73(3):968-76. Epub 2007 Dec 13. [PubMed:18079279]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Opioid receptor activity
Specific Function
Functions in lipid transport from the endoplasmic reticulum and is involved in a wide array of cellular functions probably through regulation of the biogenesis of lipid microdomains at the plasma m...
Gene Name
SIGMAR1
Uniprot ID
Q99720
Uniprot Name
Sigma non-opioid intracellular receptor 1
Molecular Weight
25127.52 Da
References
  1. Waterhouse RN, Chang RC, Atuehene N, Collier TL: In vitro and in vivo binding of neuroactive steroids to the sigma-1 receptor as measured with the positron emission tomography radioligand [18F]FPS. Synapse. 2007 Jul;61(7):540-6. [PubMed:17447254]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Kohalmy K, Tamasi V, Kobori L, Sarvary E, Pascussi JM, Porrogi P, Rozman D, Prough RA, Meyer UA, Monostory K: Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor. Drug Metab Dispos. 2007 Sep;35(9):1495-501. Epub 2007 Jun 25. [PubMed:17591676]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Binds and transactivates the retinoic acid response elements that control expression of the retinoic acid receptor beta 2 and alcohol dehydrogenase 3 genes. Transactivates both the phenobarbital re...
Gene Name
NR1I3
Uniprot ID
Q14994
Uniprot Name
Nuclear receptor subfamily 1 group I member 3
Molecular Weight
39942.145 Da
References
  1. Kohalmy K, Tamasi V, Kobori L, Sarvary E, Pascussi JM, Porrogi P, Rozman D, Prough RA, Meyer UA, Monostory K: Dehydroepiandrosterone induces human CYP2B6 through the constitutive androstane receptor. Drug Metab Dispos. 2007 Sep;35(9):1495-501. Epub 2007 Jun 25. [PubMed:17591676]
Kind
Protein
Organism
Pseudomonas putida
Pharmacological action
Unknown
General Function
Steroid delta-isomerase activity
Specific Function
Not Available
Gene Name
ksi
Uniprot ID
P07445
Uniprot Name
Steroid Delta-isomerase
Molecular Weight
14535.48 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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]
Kind
Protein
Organism
Brevibacterium sterolicum
Pharmacological action
Unknown
General Function
Steroid delta-isomerase activity
Specific Function
Catalyzes the oxidation and isomerization of cholesterol to cholestenone (4-cholesten-3-one), which is an initial step in the cholesterol degradation process.
Gene Name
choB
Uniprot ID
P22637
Uniprot Name
Cholesterol oxidase
Molecular Weight
59357.765 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. [PubMed:17139284]
  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. [PubMed:17016423]
  3. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [PubMed:10592235]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
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 performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Maenpaa J, Pelkonen O, Cresteil T, Rane A: The role of cytochrome P450 3A (CYP3A) isoform(s) in oxidative metabolism of testosterone and benzphetamine in human adult and fetal liver. J Steroid Biochem Mol Biol. 1993 Jan;44(1):61-7. [PubMed:8424894]
  3. Maenpaa J, Syngelma T, Honkakoski P, Lang MA, Pelkonen O: Comparative studies on coumarin and testosterone metabolism in mouse and human livers. Differential inhibitions by the anti-P450Coh antibody and metyrapone. Biochem Pharmacol. 1991 Aug 22;42(6):1229-35. [PubMed:1888331]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 05:05