Identification

Name
Etonogestrel
Accession Number
DB00294  (APRD00766)
Type
Small Molecule
Groups
Approved, Investigational
Description

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

Structure
Thumb
Synonyms
  • 3-Ketodesogestrel
  • 3-Oxodesogestrel
  • Etonogestrel
  • étonogestrel
  • Etonogestrelum
External IDs
ORG 3236 / ORG-3236
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
ImplanonImplant68 mg/1SubcutaneousOrganon2011-09-06Not applicableUs
NexplanonImplant68 mg/1SubcutaneousOrganon Pharmaceuticals USA2011-05-092011-05-09Us
NexplanonImplant68 mg/1SubcutaneousOrganon USA Inc.2013-09-27Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
NuvaringEtonogestrel (11.4 mg) + Ethinylestradiol (2.6 mg)RingVaginalMerck Ltd.2004-12-02Not applicableCanada
NuvaRingEtonogestrel (0.12 mg/1d) + Ethinylestradiol (0.015 mg/1d)Insert, extended releaseVaginalCentral Texas Community Health Centers2001-10-03Not applicableUs
NuvaRingEtonogestrel (0.12 mg/1d) + Ethinylestradiol (0.015 mg/1d)Insert, extended releaseVaginalOrganon2001-10-03Not applicableUs
NuvaRingEtonogestrel (11.7 mg/1) + Ethinylestradiol (2.7 mg/1)Insert, extended releaseVaginalPhysicians Total Care, Inc.2011-11-04Not applicableUs
NuvaringEtonogestrel (0.12 mg/1d) + Ethinylestradiol (0.015 mg/1d)Insert, extended releaseVaginalA-S Medication Solutions2001-10-03Not applicableUs
Categories
UNII
304GTH6RNH
CAS number
54048-10-1
Weight
Average: 324.4565
Monoisotopic: 324.20893014
Chemical Formula
C22H28O2
InChI Key
GCKFUYQCUCGESZ-BPIQYHPVSA-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
IUPAC Name
(1S,2R,10S,11S,14R,15S)-15-ethyl-14-ethynyl-14-hydroxy-17-methylidenetetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-5-one
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC(=C)[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]

Pharmacology

Indication

For use as a female contraceptive (depot).

Associated Therapies
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.

TargetActionsOrganism
AProgesterone receptor
agonist
Human
AEstrogen receptor alpha
agonist
Human
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
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinEtonogestrel may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinEtonogestrel may decrease the anticoagulant activities of (S)-Warfarin.
2,4-thiazolidinedioneThe therapeutic efficacy of 2,4-thiazolidinedione can be decreased when used in combination with Etonogestrel.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Etonogestrel.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Etonogestrel.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Etonogestrel.
6-Deoxyerythronolide BThe metabolism of Etonogestrel can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Etonogestrel.
9-aminocamptothecinThe metabolism of 9-aminocamptothecin can be decreased when combined with Etonogestrel.
AbacavirEtonogestrel may decrease the excretion rate of Abacavir which could result in a higher serum level.
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.

References

Synthesis Reference

Klaus Nickisch, "METHODS FOR THE PREPARATION OF ETONOGESTREL AND DESOGESTREL." U.S. Patent US20130123523, issued May 16, 2013.

US20130123523
General References
Not Available
External Links
Human Metabolome Database
HMDB0014439
PubChem Compound
6917715
PubChem Substance
46505321
ChemSpider
5292944
BindingDB
50423516
ChEBI
50777
ChEMBL
CHEMBL1531
Therapeutic Targets Database
DAP000855
PharmGKB
PA164771231
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Etonogestrel
ATC Codes
G03AC08 — Etonogestrel
FDA label
Download (753 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1Not Yet RecruitingPreventionContraception1
2CompletedTreatmentContraception1
2Not Yet RecruitingTreatmentContraception / Human Immunodeficiency Virus (HIV)1
2Not Yet RecruitingTreatmentContraception / Human Immunodeficiency Virus Infection(HIV)/Acquired Immunodeficiency Syndrome (AIDS)1
2TerminatedTreatmentBenign Prostatic Hyperplasia (BPH)1
3CompletedPreventionContraception3
3CompletedTreatmentContraception: Optional Applicator for Insertion of Vaginal Ring1
3RecruitingPreventionFamily Planning / Postpartum Contraception1
4Active Not RecruitingTreatmentBreastfeeding / Post Partum1
4Active Not RecruitingTreatmentSickle Cell Disorders1
4CompletedBasic ScienceContraception1
4CompletedPreventionBacterial Vaginosis (BV) / Human Immunodeficiency Virus (HIV)1
4CompletedPreventionContinuation Rate of Contraceptive Implant1
4CompletedPreventionContraception3
4CompletedTreatmentContraception2
4CompletedTreatmentContraception / Human Immunodeficiency Virus (HIV)1
4CompletedTreatmentEndometriosis1
4Not Yet RecruitingPreventionEmergency Contraception / Healthy, Reproductive Age Women1
4RecruitingBasic ScienceHormonal Contraception1
4RecruitingPreventionBacterial Vaginosis (BV)1
4TerminatedNot AvailableInfertilities1
4Unknown StatusDiagnosticHaemorrhage1
4Unknown StatusTreatmentBacterial Vaginosis (BV)1
4Unknown StatusTreatmentMenstrual Problem1
Not AvailableCompletedNot AvailableAbortion; Induced / Medical Abortion, Complete or Unspecified, Without Complication1
Not AvailableCompletedNot AvailableContraception1
Not AvailableCompletedNot AvailableContraceptive Behavior / Opiate Addiction / Pregnancy / Sexual Behavior1
Not AvailableCompletedNot AvailableContraceptive Usage / Vaginal Epithelial Disruption1
Not AvailableCompletedNot AvailableHormonal Contraception1
Not AvailableCompletedNot AvailablePharmacokinetics1
Not AvailableCompletedNot AvailablePregnancy1
Not AvailableCompletedHealth Services ResearchOvarian Follicle1
Not AvailableCompletedTreatmentContraception1
Not AvailableCompletedTreatmentHealthy Volunteers1
Not AvailableCompletedTreatmentHypermenorrhea1
Not AvailableRecruitingNot AvailableFemale Sexual Function1
Not AvailableRecruitingPreventionContraception1
Not AvailableTerminatedPreventionAdolescents Seeking Contraception / Contraception Desired1
Not AvailableTerminatedTreatmentIn-Vitro Fertilization / Infertilities1

Pharmacoeconomics

Manufacturers
  • Organon usa inc
Packagers
  • Diversified Healthcare Services Inc.
  • NV Organon
  • Organon Pharmaceuticals
Dosage forms
FormRouteStrength
ImplantSubcutaneous68 mg/1
Insert, extended releaseVaginal
RingVaginal
Prices
Unit descriptionCostUnit
Implanon 68 mg implant714.34USD each
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5150718No1992-09-292009-09-29Us
US5989581No1999-11-232018-04-08Us
US8722037No2014-05-132027-09-28Us
US8888745No2014-11-182026-08-28Us
US9757552No2017-09-122030-07-28Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP3.4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00737 mg/mLALOGPS
logP3.19ALOGPS
logP3.6ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)17.99ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity96.35 m3·mol-1ChemAxon
Polarizability37.77 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+0.9437
Caco-2 permeable+0.8167
P-glycoprotein substrateSubstrate0.6699
P-glycoprotein inhibitor IInhibitor0.6143
P-glycoprotein inhibitor IINon-inhibitor0.8387
Renal organic cation transporterNon-inhibitor0.7587
CYP450 2C9 substrateNon-substrate0.8195
CYP450 2D6 substrateNon-substrate0.9147
CYP450 3A4 substrateSubstrate0.7187
CYP450 1A2 substrateNon-inhibitor0.8898
CYP450 2C9 inhibitorNon-inhibitor0.8939
CYP450 2D6 inhibitorNon-inhibitor0.9224
CYP450 2C19 inhibitorInhibitor0.8755
CYP450 3A4 inhibitorNon-inhibitor0.7496
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5624
Ames testNon AMES toxic0.9091
CarcinogenicityNon-carcinogens0.9281
BiodegradationNot ready biodegradable0.9864
Rat acute toxicity2.1164 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8206
hERG inhibition (predictor II)Non-inhibitor0.7741
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
Predicted GC-MS Spectrum - GC-MSPredicted GC-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

Taxonomy

Description
This compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrogens and derivatives
Alternative Parents
3-oxo delta-4-steroids / 17-hydroxysteroids / Delta-4-steroids / Cyclohexenones / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Acetylides / Organic oxides / Hydrocarbon derivatives
Substituents
Estrogen-skeleton / 3-oxo-delta-4-steroid / 3-oxosteroid / 17-hydroxysteroid / Oxosteroid / Hydroxysteroid / Delta-4-steroid / Cyclohexenone / Ynone / Cyclic alcohol
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
terminal acetylenic compound, 3-oxo steroid, 3-oxo Delta(4)-steroid, 17beta-hydroxy steroid (CHEBI:50777)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Progesterone receptor ...
Gene Name
PGR
Uniprot ID
P06401
Uniprot Name
Progesterone receptor
Molecular Weight
98979.96 Da
References
  1. 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:10601100]
  2. 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:11041225]
  3. Sitruk-Ware R: Pharmacological profile of progestins. Maturitas. 2004 Apr 15;47(4):277-83. [PubMed:15063480]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
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. 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]

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]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:40