DrugBank: Etonogestrel (DB00294)

targets (2) enzymes (1)

Identification

Name

Etonogestrel

Accession Number

DB00294 (APRD00766)

Type

small molecule

Groups

approved

Description

Etonogestrel is a molecule used in hormonal contraceptives, most notably the subdermal implant Implanon. [Wikipedia]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

etonogestrel

Brand names

Implanon

Brand name mixtures

Nuvaring (Ethinyl Estradiol + Etonogestrel)

Categories

Contraceptives
Contraceptive Agents, Female

CAS number

54048-10-1

Weight

Average: 324.4565
Monoisotopic: 324.208930140

Chemical Formula

C₂₂H₂₈O₂

InChI Key

InChIKey=GCKFUYQCUCGESZ-KIIRVTSASA-N

InChI

InChI=1S/C22H28O2/c1-4-21-13-14(3)20-17-9-7-16(23)12-15(17)6-8-18(20)19(21)10-11-22(21,24)5-2/h2,12,17-20,24H,3-4,6-11,13H2,1H3/t17?,18?,19?,20?,21?,22-/m0/s1

Plain Text

IUPAC Name

(14R)-15-ethyl-14-ethynyl-14-hydroxy-17-methylidenetetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one

SMILES

CCC12CC(=C)C3C(CCC4=CC(=O)CCC34)C1CC[C@@]2(O)C#C

Plain Text

Mass Spec

Not Available

Taxonomy

Kingdom

Organic

Classes

Steroids and Steroid Derivatives

Substructures

Steroids and Steroid Derivatives
Hydroxy Compounds
Alkanes and Alkenes
Alkynes
Alcohols and Polyols
Cyclohexenes and Derivatives
Ketones

Pharmacology

Indication

For use as a female contraceptive (depot).

Pharmacodynamics

Etonogestrel is used as a female contraceptive. Etonogestrel is a progestin or a synthetic form of the naturally occurring female sex hormone, progesterone. In a woman's normal menstrual cycle, an egg matures and is released from the ovaries (ovulation). The ovary then produces progesterone, preventing the release of further eggs and priming the lining of the womb for a possible pregnancy. If pregnancy occurs, progesterone levels in the body remain high, maintaining the womb lining. If pregnancy does not occur, progesterone levels in the body fall, resulting in a menstrual period. Etonogestrel tricks the body processes into thinking that ovulation has already occurred, by maintaining high levels of the synthetic progesterone. This prevents the release of eggs from the ovaries.

Mechanism of action

Etonogestrel binds to the progesterone and estrogen receptors. Target cells include the female reproductive tract, the mammary gland, the hypothalamus, and the pituitary. Once bound to the receptor, progestins like etonogestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.

Absorption

Not Available

Volume of distribution

201 L

Protein binding

Not Available

Metabolism

Hepatic.

Route of elimination

Excretion of ENG and its metabolites, either as free steroid or as conjugates, is mainly in urine and to a lesser extent in feces.

Half life

25 hours

Clearance

Not Available

Toxicity

Symptoms of overdose include nausea, vomiting, vaginal bleeding, and other menstrual irregularities.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

Organon usa inc

Packagers

Dosage forms

Form	Route	Strength
Implant	Transdermal

Prices

Unit description	Cost	Unit
Implanon 68 mg implant	714.34 USD	each

Patents

Country	Patent Number	Approved	Expires
United States	5150718	1992-09-29	2009-09-29

Properties

State

solid

Melting point

Not Available

Experimental Properties

Property	Value	Source
logP	3.4	PhysProp

Predicted Properties

Property	Value	Source
water solubility	7.37e-03 g/l	ALOGPS
logP	3.19	ALOGPS
logP	3.52	ChemAxon Molconvert
logS	-4.64	ALOGPS
pKa	19.14	ChemAxon Molconvert
hydrogen acceptor count	2	ChemAxon Molconvert
hydrogen donor count	1	ChemAxon Molconvert
polar surface area	37.30	ChemAxon Molconvert
rotatable bond count	1	ChemAxon Molconvert
refractivity	96.35	ChemAxon Molconvert
polarizability	37.76	ChemAxon Molconvert

References

Synthesis Reference

Not Available

General Reference

Not Available

External Links

Resource	Link
PubChem Compound	40976
PubChem Substance	46505321
ChemSpider	37403
ChEBI	50777
ChEMBL	50777
Therapeutic Targets Database	DAP000855
PharmGKB	PA10908
Drug Product Database	2253186
Drugs.com	http://www.drugs.com/mtm/etonogestrel-implant.html
PDRhealth	http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/nuv1624.shtml
Wikipedia	http://en.wikipedia.org/wiki/Etonogestrel

ATC Codes

G03AC08

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

show (753 KB)

MSDS

Not Available

Interactions

Drug Interactions

Not Available

Food Interactions

Avoid alcohol.
Avoid excessive quantities of coffee or tea (Caffeine).
Increase dietary intake of magnesium, folate, vitamin B6, B12, and/or consider taking a multivitamin.
Take at the same time everyday.
Take with food.

Targets
1. Progesterone receptor Pharmacological action: yes Actions: agonist The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues Organism class: human UniProt ID: P06401 Gene: PGR Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Macpherson AM, Archer DF, Leslie S, Charnock-Jones DS, Makkink WK, Smith SK: The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium. Hum Reprod. 1999 Dec;14(12):3080-7. Pubmed Charnock-Jones DS, Macpherson AM, Archer DF, Leslie S, Makkink WK, Sharkey AM, Smith SK: The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium. Hum Reprod. 2000 Aug;15 Suppl 3:85-95. Pubmed Sitruk-Ware R: Pharmacological profile of progestins. Maturitas. 2004 Apr 15;47(4):277-83. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 2. Estrogen receptor Pharmacological action: yes Actions: agonist 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 tissues Organism class: human UniProt ID: P03372 Gene: ESR1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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

Targets

1. Progesterone receptor

Pharmacological action: yes
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out

Gene: PGR

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Macpherson AM, Archer DF, Leslie S, Charnock-Jones DS, Makkink WK, Smith SK: The effect of etonogestrel on VEGF, oestrogen and progesterone receptor immunoreactivity and endothelial cell number in human endometrium. Hum Reprod. 1999 Dec;14(12):3080-7. Pubmed
Charnock-Jones DS, Macpherson AM, Archer DF, Leslie S, Makkink WK, Sharkey AM, Smith SK: The effect of progestins on vascular endothelial growth factor, oestrogen receptor and progesterone receptor immunoreactivity and endothelial cell density in human endometrium. Hum Reprod. 2000 Aug;15 Suppl 3:85-95. Pubmed
Sitruk-Ware R: Pharmacological profile of progestins. Maturitas. 2004 Apr 15;47(4):277-83. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Estrogen receptor

Pharmacological action: yes
Actions: agonist

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 tissues

Organism class: human
UniProt ID: P03372 Link_out

Gene: ESR1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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

Enzymes
1. Cytochrome P450 3A4 Actions: substrate Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Enzymes

1. Cytochrome P450 3A4

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

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