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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:47 UTC
HMDB IDHMDB14511
Secondary Accession NumbersNone
Metabolite Identification
Common NameLevonorgestrel
DescriptionA synthetic progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. It is usually supplied in a racemic mixture (Norgestrel, 6533-00-2). Only the levonorgestrel isomer is active.
Structure
Thumb
Synonyms
ValueSource
(-)-13-Ethyl-17-hydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-oneChEBI
13-beta-Ethyl-17alpha-ethynyl-17beta-hydroxygon-4-en-3-oneChEBI
13-Ethyl-17-alpha-ethynyl-17-beta-hydroxy-4-gonen-3-oneChEBI
13-Ethyl-17-alpha-ethynylgon-4-en-17-beta-ol-3-oneChEBI
17-alpha-Ethinyl-13-beta-ethyl-17-beta-hydroxy-4-estren-3-oneChEBI
17-alpha-Ethynyl-13-ethyl-19-nortestosteroneChEBI
17-Ethynyl-18-methyl-19-nortestosteroneChEBI
17alpha-Ethynyl-13beta-ethyl-3-oxo-4-estren-17beta-olChEBI
17alpha-Ethynyl-17-hydroxy-18-methylestr-4-en-3-oneChEBI
17alpha-Ethynyl-18-homo-19-nortestosteroneChEBI
18-Methyl-17-alpha-ethynyl-19-nortestosteroneChEBI
18-MethylnorethisteroneChEBI
D(-)-NorgestrelChEBI
JadelleChEBI
LevonelleChEBI
LevonorgestrelumChEBI
LevonovaChEBI
MicrolutChEBI
MicrolutonChEBI
MicrovalChEBI
MirenaChEBI
NorLevoChEBI
Plan bChEBI
PostinorChEBI
(-)-13-Ethyl-17-hydroxy-18,19-dinor-17a-pregn-4-en-20-yn-3-oneGenerator
(-)-13-Ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-oneGenerator
13-b-Ethyl-17a-ethynyl-17b-hydroxygon-4-en-3-oneGenerator
13-β-ethyl-17α-ethynyl-17β-hydroxygon-4-en-3-oneGenerator
13-Ethyl-17-a-ethynyl-17-b-hydroxy-4-gonen-3-oneGenerator
13-Ethyl-17-α-ethynyl-17-β-hydroxy-4-gonen-3-oneGenerator
13-Ethyl-17-a-ethynylgon-4-en-17-b-ol-3-oneGenerator
13-Ethyl-17-α-ethynylgon-4-en-17-β-ol-3-oneGenerator
17-a-Ethinyl-13-b-ethyl-17-b-hydroxy-4-estren-3-oneGenerator
17-α-ethinyl-13-β-ethyl-17-β-hydroxy-4-estren-3-oneGenerator
17-a-Ethynyl-13-ethyl-19-nortestosteroneGenerator
17-α-ethynyl-13-ethyl-19-nortestosteroneGenerator
17a-Ethynyl-13b-ethyl-3-oxo-4-estren-17b-olGenerator
17α-ethynyl-13β-ethyl-3-oxo-4-estren-17β-olGenerator
17a-Ethynyl-17-hydroxy-18-methylestr-4-en-3-oneGenerator
17α-ethynyl-17-hydroxy-18-methylestr-4-en-3-oneGenerator
17a-Ethynyl-18-homo-19-nortestosteroneGenerator
17α-ethynyl-18-homo-19-nortestosteroneGenerator
18-Methyl-17-a-ethynyl-19-nortestosteroneGenerator
18-Methyl-17-α-ethynyl-19-nortestosteroneGenerator
Chemical FormulaC21H28O2
Average Molecular Weight312.4458
Monoisotopic Molecular Weight312.20893014
IUPAC Name(1S,2R,10R,11S,14R,15S)-15-ethyl-14-ethynyl-14-hydroxytetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-5-one
Traditional Nameplan b
CAS Registry Number797-63-7
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CCC(=O)C=C3CC[C@@]21[H]
InChI Identifier
InChI=1S/C21H28O2/c1-3-20-11-9-17-16-8-6-15(22)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1
InChI KeyInChIKey=WWYNJERNGUHSAO-XUDSTZEESA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as estrogens and derivatives. These are steroids with a structure containing a 3-hydroxylated estrane.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrogens and derivatives
Alternative Parents
Substituents
  • Estrogen-skeleton
  • 17-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • 3-oxosteroid
  • 3-oxo-delta-4-steroid
  • Delta-4-steroid
  • Ynone
  • Tertiary alcohol
  • Cyclic alcohol
  • Cyclic ketone
  • Ketone
  • Hydrocarbon derivative
  • Organooxygen compound
  • Carbonyl group
  • Alcohol
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External Descriptors
  • terminal acetylenic compound (CHEBI:6443 )
  • 3-oxo Delta(4)-steroid (CHEBI:6443 )
  • 17beta-hydroxy steroid (CHEBI:6443 )
  • C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C08153 )
  • Pregnane and derivatives [Fig] (C08153 )
  • C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030119 )
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Cell signaling
  • Contraceptive Agents, Female
  • Contraceptives
  • Contraceptives, Oral, Synthetic
  • Fuel and energy storage
  • Fuel or energy source
  • Membrane integrity/stability
Application
  • Nutrients
  • Pharmaceutical
  • Stabilizers
  • Surfactants and Emulsifiers
Cellular locations
  • Cytoplasm
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting Point240 °CNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.83e-03 g/LNot Available
LogP3.8Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0058 mg/mLALOGPS
logP3.25ALOGPS
logP3.66ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)17.91ChemAxon
pKa (Strongest Basic)-1.5ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area37.3 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity92.03 m3·mol-1ChemAxon
Polarizability36.73 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
1D NMR13C NMR SpectrumNot Available
Biological Properties
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00367
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00367
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-3 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00367
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID12560
KEGG Compound IDC08149
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevonorgestrel
NuGOwiki LinkHMDB14511
Metagene LinkHMDB14511
METLIN IDNot Available
PubChem Compound13109
PDB IDNOG
ChEBI ID6443
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Sitruk-Ware R: New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. Epub 2005 Nov 16. [16291771 ]
  2. Edgren RA, Stanczyk FZ: Nomenclature of the gonane progestins. Contraception. 1999 Dec;60(6):313. [10715364 ]
  3. FDA label.

Enzymes

General function:
Involved in 3-oxo-5-alpha-steroid 4-dehydrogenase activity
Specific function:
Converts testosterone into 5-alpha-dihydrotestosterone and progesterone or corticosterone into their corresponding 5-alpha-3-oxosteroids. It plays a central role in sexual differentiation and androgen physiology.
Gene Name:
SRD5A1
Uniprot ID:
P18405
Molecular weight:
29458.18
References
  1. Hammond GL, Rabe T, Wagner JD: Preclinical profiles of progestins used in formulations of oral contraceptives and hormone replacement therapy. Am J Obstet Gynecol. 2001 Aug;185(2 Suppl):S24-31. [11521119 ]
  2. Rabe T, Kowald A, Ortmann J, Rehberger-Schneider S: Inhibition of skin 5 alpha-reductase by oral contraceptive progestins in vitro. Gynecol Endocrinol. 2000 Aug;14(4):223-30. [11075290 ]
General function:
Involved in monooxygenase 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 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. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular weight:
57255.585
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. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in monooxygenase activity
Specific function:
Catalyzes the formation of aromatic C18 estrogens from C19 androgens.
Gene Name:
CYP19A1
Uniprot ID:
P11511
Molecular weight:
57882.48
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. Epub 2009 Nov 24. [19934256 ]
General function:
Involved in DNA 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 factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3
Gene Name:
AR
Uniprot ID:
P10275
Molecular weight:
98987.9
References
  1. Shields-Botella J, Duc I, Duranti E, Puccio F, Bonnet P, Delansorne R, Paris J: An overview of nomegestrol acetate selective receptor binding and lack of estrogenic action on hormone-dependent cancer cells. J Steroid Biochem Mol Biol. 2003 Nov;87(2-3):111-22. [14672731 ]
  2. Freyberger A, Witters H, Weimer M, Lofink W, Berckmans P, Ahr HJ: Screening for (anti)androgenic properties using a standard operation protocol based on the human stably transfected androgen sensitive PALM cell line. First steps towards validation. Reprod Toxicol. 2010 Aug;30(1):9-17. Epub 2009 Oct 27. [19836445 ]
  3. Freyberger A, Weimer M, Tran HS, Ahr HJ: Assessment of a recombinant androgen receptor binding assay: initial steps towards validation. Reprod Toxicol. 2010 Aug;30(1):2-8. Epub 2009 Oct 13. [19833195 ]
  4. Kloosterboer HJ, Vonk-Noordegraaf CA, Turpijn EW: Selectivity in progesterone and androgen receptor binding of progestagens used in oral contraceptives. Contraception. 1988 Sep;38(3):325-32. [3139361 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
Specific function:
Isoform A is inactive in stimulating c-Src/MAPK signaling on hormone stimulation
Gene Name:
PGR
Uniprot ID:
P06401
Molecular weight:
98980.0
References
  1. Maruo T, Ohara N, Matsuo H, Xu Q, Chen W, Sitruk-Ware R, Johansson ED: Effects of levonorgestrel-releasing IUS and progesterone receptor modulator PRM CDB-2914 on uterine leiomyomas. Contraception. 2007 Jun;75(6 Suppl):S99-103. Epub 2007 Mar 21. [17531625 ]
  2. Mirkin S, Wong BC, Archer DF: Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells. Fertil Steril. 2005 Aug;84(2):485-91. [16084894 ]
  3. Hompes PG, Mijatovic V: Endometriosis: the way forward. Gynecol Endocrinol. 2007 Jan;23(1):5-12. [17484506 ]
  4. Creinin MD, Schlaff W, Archer DF, Wan L, Frezieres R, Thomas M, Rosenberg M, Higgins J: Progesterone receptor modulator for emergency contraception: a randomized controlled trial. Obstet Gynecol. 2006 Nov;108(5):1089-97. [17077229 ]
  5. Bray JD, Jelinsky S, Ghatge R, Bray JA, Tunkey C, Saraf K, Jacobsen BM, Richer JK, Brown EL, Winneker RC, Horwitz KB, Lyttle CR: Quantitative analysis of gene regulation by seven clinically relevant progestins suggests a highly similar mechanism of action through progesterone receptors in T47D breast cancer cells. J Steroid Biochem Mol Biol. 2005 Dec;97(4):328-41. Epub 2005 Sep 12. [16157482 ]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
General function:
Involved in sequence-specific DNA binding transcription factor activity
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 tissues. Can activate the transcriptional activity of TFF1
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular weight:
66215.4
References
  1. Vereide AB, Kaino T, Sager G, Arnes M, Orbo A: Effect of levonorgestrel IUD and oral medroxyprogesterone acetate on glandular and stromal progesterone receptors (PRA and PRB), and estrogen receptors (ER-alpha and ER-beta) in human endometrial hyperplasia. Gynecol Oncol. 2006 May;101(2):214-23. Epub 2005 Dec 1. [16325240 ]
  2. Mirkin S, Wong BC, Archer DF: Effect of 17 beta-estradiol, progesterone, synthetic progestins, tibolone, and tibolone metabolites on vascular endothelial growth factor mRNA in breast cancer cells. Fertil Steril. 2005 Aug;84(2):485-91. [16084894 ]
  3. Abdel-Aleem H, Shaaban OM, Amin AF, Abdel-Aleem AM: Tamoxifen treatment of bleeding irregularities associated with Norplant use. Contraception. 2005 Dec;72(6):432-7. Epub 2005 Aug 9. [16307966 ]
  4. Sun D, Yan C, Jacobson A, Jiang H, Carroll MA, Huang A: Contribution of epoxyeicosatrienoic acids to flow-induced dilation in arteries of male ERalpha knockout mice: role of aromatase. Am J Physiol Regul Integr Comp Physiol. 2007 Sep;293(3):R1239-46. Epub 2007 Jul 18. [17634204 ]
  5. Vijayanathan V, Venkiteswaran S, Nair SK, Verma A, Thomas TJ, Zhu BT, Thomas T: Physiologic levels of 2-methoxyestradiol interfere with nongenomic signaling of 17beta-estradiol in human breast cancer cells. Clin Cancer Res. 2006 Apr 1;12(7 Pt 1):2038-48. [16609013 ]