PRASTERONE

First approved in 2014

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C19H28O2
Molecular Weight	288.4244
Optical Activity	UNSPECIFIED
Defined Stereocenters	6 / 6
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CCC(=O)[C@@]1(C)CC[C@@]3([H])[C@@]2([H])CC=C4C[C@@H](O)CC[C@]34C

InChI

InChIKey=FMGSKLZLMKYGDP-USOAJAOKSA-N

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

HIDE SMILES / InChI

Description
Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208470s000lbl.pdf
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/mesh/68003687 | http://www.hmdb.ca/metabolites/HMDB00077

Dehydroepiandrosterone (INTRAROSA™, prasterone) is a major C19 steroid produced from cholesterol by the adrenal cortex. It is also produced in small quantities in the testis and the ovary. Dehydroepiandrosterone (INTRAROSA, prasterone) is structurally similar to, and is a precursor of, androstenedione, testosterone, estradiol, estrone and estrogen. It indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. The mechanism of action of dehydroepiandrosterone (INTRAROSA, prasterone) in postmenopausal women with vulvar and vaginal atrophy is not fully established.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Estrogen receptor beta 110 Target ID: CHEMBL242 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15994348	Agonist 2678	514.55 nM [Ki]
Estrogen receptor alpha 127 Target ID: CHEMBL206 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15994348	Partial Agonist 290	1053.17 nM [Ki]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15994348	Antagonist 2778	1177.02 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Dyspareunia 7 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/208470s000lbl.pdf	Primary		Approved 8429	INTRAROSA Approved Use INTRAROSA™ is a steroid indicated for the treatment of moderate to severe dyspareunia, a symptom of vulvar and vaginal atrophy, due to menopause. Launch Date 2016

C_max

Value	Dose	Co-administered	Analyte	Population
36.7 nM EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10372727	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		PRASTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
176.1 nM × h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10372727	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		PRASTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Co-administered	Analyte	Population
5.35 h EXPERIMENT https://www.ncbi.nlm.nih.gov/pubmed/10372727	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:		PRASTERONE serum	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

Doses

Dose	Population	Adverse events
1600 mg 1 times / day multiple, oral Highest studied dose Dose: 1600 mg, 1 times / day Route: oral Route: multiple Dose: 1600 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/2961787	healthy, 22-25 years n = 5 Health Status: healthy Age Group: 22-25 years Sex: M Population Size: 5 Sources: https://pubmed.ncbi.nlm.nih.gov/2961787	Sources: https://pubmed.ncbi.nlm.nih.gov/2961787
400 mg 1 times / day multiple, oral Dose: 400 mg, 1 times / day Route: oral Route: multiple Dose: 400 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/16784956	unhealthy, 44.9 years n = 29 Health Status: unhealthy Condition: HIV infection Age Group: 44.9 years Sex: M Population Size: 29 Sources: https://pubmed.ncbi.nlm.nih.gov/16784956	Sources: https://pubmed.ncbi.nlm.nih.gov/16784956

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 1587	inhibitor 1767	inhibitor 1852

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 1524 CYP2A6 707 CYP2B6 810 CYP2C8 911 CYP2C19 1478 CYP2E1 882	17-beta-HSD1 6 5-alpha-reductase 1 6 CYP19A1 23 UGT 192 sulfotransferases 38 17-beta-HSD3 6 17-beta-HSD5 6 17-beta-HSD2 10 17-beta-HSD13 6 5-alpha-reductase 2 6 3-beta-HSD1 6 3-alpha-HSD1 6 3-alpha-HSD3 10 UGT2B28 63 UGT2B15 203 UGT2B17 213 UGT1A1 418

Drug as perpetrator

Target	Modality	Activity
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	no

Drug as victim

Target	Modality	Activity
17-beta-HSD1 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
17-beta-HSD13 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
17-beta-HSD2 10	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
17-beta-HSD3 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
17-beta-HSD5 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
3-alpha-HSD1 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
3-alpha-HSD3 10	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
3-beta-HSD1 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
5-alpha-reductase 1 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	yes
5-alpha-reductase 2 6	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=8 Page: 8.0	yes
CYP19A1 23	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=4 Page: 4.0	yes
UGT 192	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes
UGT1A1 418	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
UGT2B15 203	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
UGT2B17 213	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
UGT2B28 63	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000PharmR.pdf#page=8 Page: 8.0	yes
sulfotransferases 38	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2016/208470Orig1s000ClinPharmR.pdf#page=9 Page: 9.0	yes

Sourcing

Vendor/Aggregator	ID	URL
AEchem Scientific Corp., USA	AE1-000705	http://www.aechemsc.com/info_products/AE1-000705.php
AHH Chemical co.,ltd	MT-00368	http://www.ahhchemical.com/product/MT-00368.html
AHH Chemical co.,ltd	MT-07566	http://www.ahhchemical.com/product/MT-07566.html
AK Scientific, Inc. (AKSCI)	70793	http://www.aksci.com/item_detail.php?cat=70793
AK Scientific, Inc. (AKSCI)	J10065	http://www.aksci.com/item_detail.php?cat=J10065
Aaron Chemicals	AR0039QK	http://www.aaronchem.com/53-43-0
AbMole Bioscience	M9061	http://www.abmole.com/products/dehydroepiandrosterone.html
Acadechem	ACDS-064086	http://www.acadechemical.com/product/138785
Achemo Scientific Limited	AC-15211	http://www.achemo.com/product_view.asp?ID=5101
Achemtek	0104-014342	http://www.achemtek.com/53-43-0
Acorn PharmaTech	ACN-036240	http://www.acornpharmatech.com/
Acros Organics	AC154980025	https://www.fishersci.com/shop/products/dehydroisoandrosterone-99-acros-organics-1/AC154980025
Acros Organics	AC154980100	https://www.fishersci.com/shop/products/dehydroisoandrosterone-99-acros-organics-1/AC154980100
Acros Organics	AC154980500	https://www.fishersci.com/shop/products/dehydroisoandrosterone-99-acros-organics/AC154980500
Alfa Chemistry	53-43-0	https://www.alfa-chemistry.com/dehydroepiandrosterone-cas-53-43-0-item-79560.htm
Alsachim	3710	http://www.alsachim.com/product-C5001-glo.bal-view.html
Ansion Pharma	53-43-0	http://www.ansionpharma.com/English/Product/0974815742.html
ApexBio Technology	B1375	http://www.apexbt.com/dehydroepiandrosterone-dhea.html
Aurora Fine Chemicals LLC	A17.877.349	http://online.aurorafinechemicals.com/info?ID=A17.877.349
Aurum Pharmatech LLC	M-1336	http://www.Aurumpharmatech.com/Product/ProductDetails/M_1336
AvaChem Scientific	3973	http://www.avachem.com/productSearch.asp?3973
BioChemPartner	BCP02453	http://www.biochempartner.com/53-43-0-BCP02453
BioSynth	D-0340	https://www.biosynth.com/en/products/life-science/other-biochemicals/products/D-0340.html
Chem Scene	CS-1667	http://www.chemscene.com/53-43-0.html
ChemFaces	CFN90043	http://www.chemfaces.com/natural/Dehydroepiandrosterone-CFN90043.html
ChemMol	30100413	http://www.chemmol.com/chemmol/30100413.html
Chemspace	CSSS00000029485	https://chem-space.com/CSSS00000029485
DC Chemicals	DC5201	http://www.dcchemicals.com/product_show-Dehydroepiandrosterone_DHEA_.html
Enamine	Z2213891300	https://www.enaminestore.com/catalog/Z2213891300
Glentham Life Sciences	GP0612	http://www.glentham.com/products/product/GP0612/
LGC Standards	DRE-C16286250	https://www.lgcstandards.com/US/en/p/DRE-C16286250
LGC Standards	LGCAMP0651.00-11	https://www.lgcstandards.com/US/en/p/LGCAMP0651.00-11
LGC Standards	LGCFOR0651.00	https://www.lgcstandards.com/US/en/p/LGCFOR0651.00
LGC Standards	MM0651.00-0250	https://www.lgcstandards.com/US/en/p/MM0651.00-0250
Matrix Scientific	89314	https://www.matrixscientific.com/089314.html
MedChem Express	HY-14650	https://www.medchemexpress.com/DHEA.html
MuseChem	A000700	https://www.musechem.com/product/A000700.html
Octagon Chemicals	API Dehydroepiandrosterone 53-43-0	https://octagonchem.com/
Parchem	18496	http://www.parchem.com/chemical-supplier-distributor/DHEA-008496.aspx
Parchem	10897	http://www.parchem.com/chemical-supplier-distributor/Dehydroepiandrosterone-000897.aspx
Sigma-Aldrich	D-063_CERILLIAN	https://www.sigmaaldrich.com/catalog/product/cerillian/d063?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sigma-Aldrich	D4000_SIGMA	https://www.sigmaaldrich.com/catalog/product/sigma/d4000?utm_source=pubchem&utm_campaign=pubchem_2017&utm_medium=referral
Sinfoo Biotech	S048429	http://www.sinfoobiotech.com/product/1051827
Smolecule	S525573	http://www.smolecule.com/products/s525573
THE BioTek	bt-266623	https://www.thebiotek.com/product/inhibitors/bt-266623
VladaChem	VL162585	https://www.vladachem.com/product.php?products=53-43-0
VladaChem	VL277861-1G	https://www.vladachem.com/product.php?products=53-43-0
W&J PharmaChem	100968	http://www.wjpharmachem.com/new/100968.html
eNovation Chemicals	K39145	https://www.enovationchem.com/ProductDetails.asp?ProductID=K39145
iChemical	EBD1328208	http://www.ichemical.com/products/53-43-0.html?utm_source=PubChem&utm_medium=website&utm_campaign=product%20catalogs

PubMed

Title	Date	PubMed
The steroid hormone dehydroepiandrosterone inhibits CYP1A1 expression in vitro by a post-transcriptional mechanism.	1999 Dec 3	10575002
Dehydroepiandrosterone suppresses elevated hepatic glucose-6-phosphatase mRNA level in C57BL/KsJ-db/db mice: comparison with troglitazone.	2000 Dec	11228057
Differential estrogen receptor binding of estrogenic substances: a species comparison.	2000 Nov 15	11162928
Inhibition of human immunodeficiency virus type-1 (HIV-1) replication by immunor (IM28), a new analog of dehydroepiandrosterone.	2000 Oct-Dec	11200288
The use of estrogen, DHEA, and diosgenin in a sustained delivery setting as a novel treatment approach for osteoporosis in the ovariectomized adult rat model.	2001	11347403
Intraadrenal mechanisms of DHEA regulation: a hypothesis for adrenopause.	2001	11341302
Effects of transdermal application of 7-oxo-DHEA on the levels of steroid hormones, gonadotropins and lipids in healthy men.	2001	11300231
Dehydroepiandrosterone sulphate prevents oxygen-glucose deprivation-induced injury in cerebellar granule cell culture.	2001	11166128
Therapeutic strategies in adrenal insufficiency.	2001 Apr	11353897
High-grade prostate cancer is associated with low serum testosterone levels.	2001 Apr	11304729
Sarcopenia.	2001 Apr	11283518
cyp7b1 catalyses the 7alpha-hydroxylation of dehydroepiandrosterone and 25-hydroxycholesterol in rat prostate.	2001 Apr 15	11284740
Dehydroepiandrosterone decreases mortality rate and improves cellular immune function during polymicrobial sepsis.	2001 Feb	11246320
Hormone replacement therapy and fractures in older adults.	2001 Feb	11207873
Corticotrophin-releasing hormone and ACTH levels in maternal and fetal blood during spontaneous and oxytocin-induced labour.	2001 Feb	11182747
Long-term dehydroepiandrosterone and 16alpha-fluoro-5-androsten-17-one administration enhances DNA synthesis and induces expression of c-fos and c-Ha-ras in a selected population of preneoplastic lesions in liver of diethylnitrosamine-initiated rats.	2001 Feb	11181452
Bacterial expression, purification, and characterization of rat hydroxysteroid sulfotransferase STa.	2001 Feb	11162411
Enhanced induction of the IgA response in pigs by calcitriol after intramuscular immunization.	2001 Feb 28	11228356
Differentially expressed genes in zona reticularis cells of the human adrenal cortex.	2001 Feb 28	11223184
Dehydroepiandrosterone stimulates proliferation and gene expression in MCF-7 cells after conversion to estradiol.	2001 Feb 28	11223173
Composite effects of group drumming music therapy on modulation of neuroendocrine-immune parameters in normal subjects.	2001 Jan	11191041
Preliminary studies on the effect of dehydroepiandrosterone (DHEA) on both constitutive and phytohaemagglutinin (PHA)-inducible IL-6 and IL-2 mRNA expression and cytokine production in human spleen mononuclear cell suspensions in vitro.	2001 Jan	11167994
Effects of long-term alpha-tocopherol supplementation on serum hormones in older men.	2001 Jan 1	11170129
Low dehydroepiandrosterone and ischemic heart disease in middle-aged men: prospective results from the Massachusetts Male Aging Study.	2001 Jan 1	11159150
Steroidogenic response of adrenal tissues after administration of ACTH to dogs with hypercortisolemia.	2001 Jan 15	11195825
Crucial role of cytokines in sex steroid formation in normal and tumoral tissues.	2001 Jan 22	11165008
[Precocious puberty caused by a testicular Leydig cell tumor].	2001 Jan 28	11232155
Receptor selectivity, enzymes and tissue specificity.	2001 Jan 31	11173175
Chalcones are potent inhibitors of aromatase and 17beta-hydroxysteroid dehydrogenase activities.	2001 Jan 5	11205867
Hormonal decline in elderly men and male menopause.	2001 Jan-Feb	11223793
Plasma levels of neuroactive steroids are increased in untreated women with anorexia nervosa or bulimia nervosa.	2001 Jan-Feb	11211066
Circulating plasma leptin and IGF-1 levels in girls with premature adrenarche: potential implications of a preliminary study.	2001 Mar	11355746
Exploratory biochemical data analysis: a comparison of two sample means and diagnostic displays.	2001 Mar	11350023
Sex hormone-binding globulin as a marker of the effect of hormonal treatment in Turner's syndrome.	2001 Mar	11308992
Association of vitamin D receptor and 17 hydroxylase gene polymorphisms with benign prostatic hyperplasia and benign prostatic enlargement.	2001 Mar	11248649
Enhanced dehydroepiandrosterone synthesis by amnion compared to chorion: a comparative study using the reverse-isotope dilution technique.	2001 Mar	11170268
Ergogenic aids: counseling the athlete.	2001 Mar 1	11261867
Dehydroepiandrosterone replacement in women with adrenal insufficiency: effects on body composition, serum leptin, bone turnover, and exercise capacity.	2001 May	11344193
Identification and characterization of human organic anion transporter 3 expressing predominantly in the kidney.	2001 May	11306713
Dehydroepiandrosterone restores hepatocellular function and prevents liver damage in estrogen-deficient females following trauma and hemorrhage.	2001 May 15	11341799
Serum hormones and the alcohol-breast cancer association in postmenopausal women.	2001 May 2	11333294
Anorectic effect of dehydroepiandrosterone combined with dexfenfluramine or thionisoxetine.	2001 May 4	11348631

Patents

Sample Use Guides

In Vivo Use Guide

Administer one INTRAROSA vaginal insert once daily at bedtime, using the provided applicator.

Route of Administration: Vaginal

In Vitro Use Guide

Dehydroepiandrosterone (DHEA) bound to AR with a Ki of 1 microM, which was associated with AR transcriptional antagonism on both the mouse mammary tumor virus and prostate-specific antigen promoters. DHEA bound to ERalpha and ERbeta, with Ki values of 1.1 and 0.5 microM, respectively. Despite the similar binding affinities, DHEA showed preferential agonism of ERbeta with an EC50 of approximately 200 nm and maximal activation at 1 microM. With ERalpha 30-70% agonism at 5 microM was found.

Name

Type

Language

PRASTERONE

Official Name

English

DEHYDROEPIANDROSTERONE [MI]

Common Name

English

EM-760

Code

English

BIOLAIF

Brand Name

English

PRASTERONE [MART.]

Common Name

English

DEHYDROEPIANDROSTERONE

Common Name

English

PRASTERONE [INCI]

Common Name

English

3β-Hydroxyandrost-5-en-17-one

Systematic Name

English

DHEA

Common Name

English

PRASTERONE [ORANGE BOOK]

Common Name

English

INTRAROSA

Brand Name

English

ANDROST-5-EN-17-ONE, 3-HYDROXY-, (3.BETA.)-

Systematic Name

English

NSC-9896

Code

English

DEHYDROANDROSTERONE

Common Name

English

DEHYDROISOANDROSTERONE

Common Name

English

DEHYDROEPIANDROSTERONE [VANDF]

Common Name

English

Prasterone [WHO-DD]

Common Name

English

PRASTERONE [USAN]

Common Name

English

prasterone [INN]

Common Name

English

VAGINORM

Brand Name

English

Classification Tree Code System Code

LOINC

35206-2