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Record Information
Version2.0
Creation Date2014-09-11 05:14:42 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4749
Identification
Common NameLevonorgestrel
ClassSmall Molecule
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. Levonorgestrel is marketed mostly as a combination oral contraceptive under several brand names such as Alesse, Triphasil, and Min-Ovral.
Compound Type
  • Contraceptive Agent
  • Contraceptive Agent, Female
  • Contraceptive, Oral, Synthetic
  • Drug
  • Ester
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
Synonyms
Synonym
(-)-13-Ethyl-17-hydroxy-18,19-dinor-17alpha-pregn-4-en-20-yn-3-one
(8R,9S,10R,13S,14S,17R)-13-ethyl-17-ethynyl-17-hydroxy- 1,2,6,7,8,9,10,11,12,13,14,15,16, 17- tetradecahydrocyclopenta[a] phenanthren-3-one
13-beta-Ethyl-17alpha-ethynyl-17beta-hydroxygon-4-en-3-one
13-Ethyl-17-alpha-ethynyl-17-beta-hydroxy-4-gonen-3-one
13-Ethyl-17-alpha-ethynylgon-4-en-17-beta-ol-3-one
17-alpha-Ethinyl-13-beta-ethyl-17-beta-hydroxy-4-estren-3-one
17-alpha-Ethynyl-13-ethyl-19-nortestosterone
17-Ethynyl-18-methyl-19-nortestosterone
17alpha-Ethynyl-13beta-ethyl-3-oxo-4-estren-17beta-ol
17alpha-Ethynyl-17-hydroxy-18-methylestr-4-en-3-one
17alpha-Ethynyl-18-homo-19-nortestosterone
18-Methyl-17-alpha-ethynyl-19-nortestosterone
18-Methylnorethisterone
D(-)-Norgestrel
Jadelle
Levonelle
Levonorgestrelum
Levonova
Medonor
Microlut
Microluton
Microval
Mirena
Neogest
Next Choice
Norgeston
NorLevo
Norplant
Plan b
Postinor
Skyla
Chemical FormulaC21H28O2
Average Molecular Mass312.446 g/mol
Monoisotopic Mass312.209 g/mol
CAS Registry Number797-63-7
IUPAC Name(1S,2R,10R,11S,14R,15S)-15-ethyl-14-ethynyl-14-hydroxytetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
Traditional Name(1S,2R,10R,11S,14R,15S)-15-ethyl-14-ethynyl-14-hydroxytetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-5-one
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 IdentifierInChI=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
Description 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
  • 3-oxo-delta-4-steroid
  • 3-oxosteroid
  • 17-hydroxysteroid
  • Oxosteroid
  • Hydroxysteroid
  • Delta-4-steroid
  • Cyclohexenone
  • Ynone
  • Cyclic alcohol
  • Tertiary alcohol
  • Cyclic ketone
  • Ketone
  • Acetylide
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Carbonyl group
  • Alcohol
  • Organooxygen compound
  • 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 )
  • Pregnane and derivatives [Fig] (C08153 )
  • C21 steroids (gluco/mineralocorticoids, progestogens) and derivatives (C08153 )
  • C21 steroids (gluco/mineralocorticoids, progestogins) and derivatives (LMST02030119 )
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cytoplasm
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point240°C
Boiling PointNot Available
Solubility2.05 mg/L
LogP3.8
Predicted Properties
PropertyValueSource
Water Solubility0.0058 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity92.03 m³·mol⁻¹ChemAxon
Polarizability36.75 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-001i-0490000000-497c4ebd506c0b9c8ec3JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-0a4l-1259000000-2a7acf9f8fd01faadc86JSpectraViewer
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-066r-0931000000-4a863e895a5edd6cebebJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-03di-0439000000-bcbc7c657a115dced40aJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a5a-3920000000-edbd3785e7d20d9e81beJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0a4i-2920000000-a08b14b6d762cf4c42b1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-0002-0900000000-ccbe00eb6d33f44bf13eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-03dj-0809000000-3b4f03aa1582c55a88a4JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 45V, Positivesplash10-0a59-2910000000-2e210ea979850c3d19acJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-0002-0900000000-87a5333787ffe2461b52JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 30V, Positivesplash10-03dj-1943000000-e4eeb86036aa8456827fJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-06r2-0932000000-542d94c4f65730336be8JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-0002-0900000000-d9c9cc75f7d652292590JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-0002-0900000000-a5a5bd10465f22e61a65JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Positivesplash10-03di-0009000000-0d184562b2bcf62fab5cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-055f-7900000000-2c2242a1883d4b23fb14JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-0a5c-4900000000-64d2115a1e9554b15780JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-05po-9700000000-f172af0f505e7230dfccJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-03di-0009000000-73765d8e0531c2c94251JSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-03di-0179000000-09f92950350c9411f4dcJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0btj-0191000000-7bd7256abde150b22d9fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0f76-2390000000-84a923da67ade6ef90a8JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0019000000-3f0cb0e2e76214741c6fJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0059000000-f6e5c83ac4c0da584cb2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-053v-0090000000-6bb0ea8f0fc81b4c6fe2JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-03di-0009000000-152b659b4891e36b54f3JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-03di-0019000000-51b6ec5de157050ca35eJSpectraViewer
1D NMR13C NMR SpectrumNot AvailableJSpectraViewer
Toxicity Profile
Route of ExposureLevonorgestrel is not subjected to a "first-pass" effect and is virtually 100% bioavailable.
Mechanism of ToxicityBinds 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 levonorgestrel will slow the frequency of release of gonadotropin releasing hormone (GnRH) from the hypothalamus and blunt the pre-ovulatory LH (luteinizing hormone) surge.
MetabolismHepatic. Route of Elimination: About 45% of levonorgestrel and its metabolites are excreted in the urine and about 32% are excreted in feces, mostly as glucuronide conjugates.
Toxicity ValuesLD50 >5000 mg/kg (orally in rats)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)Norgestrel: Group 2B, possibly carcinogenic to humans. (4)
Uses/SourcesFor the treatment of menopausal and postmenopausal disorders and alone or in combination with other hormones as an oral contraceptive.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00367
HMDB IDHMDB14511
PubChem Compound ID13109
ChEMBL IDCHEMBL1389
ChemSpider ID12560
KEGG IDC08149
UniProt IDNot Available
OMIM ID
ChEBI ID6443
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNOG
ACToR IDNot Available
Wikipedia LinkLevonorgestrel
References
Synthesis Reference

Yu-Sheng Chang, Shu-Ping Chen, “Levonorgestrel Crystallization.” U.S. Patent US20090069584, issued March 12, 2009.

MSDSLink
General References
  1. Edgren RA, Stanczyk FZ: Nomenclature of the gonane progestins. Contraception. 1999 Dec;60(6):313. [10715364 ]
  2. Sitruk-Ware R: New progestagens for contraceptive use. Hum Reprod Update. 2006 Mar-Apr;12(2):169-78. Epub 2005 Nov 16. [16291771 ]
  3. FDA label.
  4. International Agency for Research on Cancer (2014). IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Electron carrier 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 Da
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:
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 factor activity is modulated by bound coactivator and corepressor proteins. Transcription activation is down-regulated by NR0B2. Activated, but not phosphorylated, by HIPK3 and ZIPK/DAPK3.
Gene Name:
AR
Uniprot ID:
P10275
Molecular Weight:
98987.9 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0507 uMATG_AR_TRANSAttagene
AC500.00131 uMNVS_NR_hARNovascreen
AC500.00356 uMOT_AR_ARSRC1_0480Odyssey Thera
AC500.0034 uMOT_AR_ARSRC1_0960Odyssey Thera
AC500.0225 uMTox21_AR_BLA_Antagonist_ratioTox21/NCGC
AC500.00118 uMTox21_AR_LUC_MDAKB2_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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 isoform B (PRB) is involved activation of c-SRC/MAPK signaling on hormone stimulation.Isoform A: inactive in stimulating c-Src/MAPK signaling on hormone stimulation.Isoform 4: Increases mitochondrial membrane potential and cellular respiration upon stimulation by progesterone.
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0229 uMNVS_NR_hPRNovascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Zinc ion binding
Specific Function:
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modulator of other transcription factors. Affects inflammatory responses, cellular proliferation and differentiation in target tissues. Could act as a coactivator for STAT5-dependent transcription upon growth hormone (GH) stimulation and could reveal an essential role of hepatic GR in the control of body growth. Involved in chromatin remodeling. May play a negative role in adipogenesis through the regulation of lipolytic and antilipogenic genes expression.
Gene Name:
NR3C1
Uniprot ID:
P04150
Molecular Weight:
85658.57 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.0238 uMNVS_NR_hGRNovascreen
AC500.108 uMTox21_GR_BLA_Antagonist_ratioTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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 tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of the CCL2 and IL8 promoters and can displace CREBBP. Present with NF-kappa-B components RELA/p65 and NFKB1/p50 on ERE sequences. Can also act synergistically with NF-kappa-B to activate transcription involving respective recruitment adjacent response elements; the function involves CREBBP. Can activate the transcriptional activity of TFF1. Also mediates membrane-initiated estrogen signaling involving various kinase cascades. Isoform 3 is involved in activation of NOS3 and endothelial nitric oxide production. Isoforms lacking one or several functional domains are thought to modulate transcriptional activity by competitive ligand or DNA binding and/or heterodimerization with the full length receptor. Essential for MTA1-mediated transcriptional regulation of BRCA1 and BCAS3. Isoform 3 can bind to ERE and inhibit isoform 1.
Gene Name:
ESR1
Uniprot ID:
P03372
Molecular Weight:
66215.45 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.101 uMACEA_T47D_80hr_PositiveACEA Biosciences
AC500.708 uMATG_ERa_TRANSAttagene
AC500.542 uMATG_ERE_CISAttagene
AC500.751 uMNVS_NR_hERNovascreen
AC500.908 uMTox21_ERa_BLA_Agonist_ratioTox21/NCGC
AC500.0587 uMTox21_ERa_LUC_BG1_AgonistTox21/NCGC
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC500.481 uMNVS_ADME_hCYP2C19Novascreen
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]
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 and secretion of potentially harmful xenobiotics, drugs and endogenous compounds. Activated by the antibiotic rifampicin and various plant metabolites, such as hyperforin, guggulipid, colupulone, and isoflavones. Response to specific ligands is species-specific. Activated by naturally occurring steroids, such as pregnenolone and progesterone. Binds to a response element in the promoters of the CYP3A4 and ABCB1/MDR1 genes.
Gene Name:
NR1I2
Uniprot ID:
O75469
Molecular Weight:
49761.245 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
AC502.14 uMATG_PXR_TRANSAttagene
AC504.84 uMATG_PXRE_CISAttagene
References
  1. Sipes NS, Martin MT, Kothiya P, Reif DM, Judson RS, Richard AM, Houck KA, Dix DJ, Kavlock RJ, Knudsen TB: Profiling 976 ToxCast chemicals across 331 enzymatic and receptor signaling assays. Chem Res Toxicol. 2013 Jun 17;26(6):878-95. doi: 10.1021/tx400021f. Epub 2013 May 16. [23611293 ]