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Identification
NameNorelgestromin
Accession NumberDB06713
TypeSmall Molecule
GroupsApproved
DescriptionNorelgestromin is a drug used in contraception. Norelgestromin is the active progestin responsible for the progestational activity that occurs in women after application of ORTHO EVRA patch.
Structure
Thumb
Synonyms
17-Deacetylnorgestimate
17-Deacylnorgestimate
18-Methylnorethindrone oxime
D-Norgestrel 3-oxime
Deacetylnorgestimate
Levonorgestrel 3-oxime
Levonorgestrel oxime
Norplant 3-oxime
External Identifiers
  • BRN 4202099
  • RWJ 10553
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International BrandsNot Available
Brand mixtures
NameLabellerIngredients
Evra -(6/0.60)Janssen Inc
Evra -(6/0.75)Janssen Inc
Ortho EvraJanssen Pharmaceutical, Inc.
XulaneMylan Pharmaceuticals Inc.
SaltsNot Available
Categories
UNIIR0TAY3X631
CAS number53016-31-2
WeightAverage: 327.468
Monoisotopic: 327.219829178
Chemical FormulaC21H29NO2
InChI KeyISHXLNHNDMZNMC-XUDSTZEESA-N
InChI
InChI=1S/C21H29NO2/c1-3-20-11-9-17-16-8-6-15(22-24)13-14(16)5-7-18(17)19(20)10-12-21(20,23)4-2/h2,13,16-19,23-24H,3,5-12H2,1H3/t16-,17+,18+,19-,20-,21-/m0/s1
IUPAC Name
(1S,2R,10R,11S,14R,15S)-15-ethyl-14-ethynyl-5-(hydroxyimino)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]heptadec-6-en-14-ol
SMILES
[H][C@@]12CC[C@@](O)(C#C)[C@@]1(CC)CC[C@]1([H])[C@@]3([H])CCC(C=C3CC[C@@]21[H])=NO
Pharmacology
IndicationNorelgestromin is used for contraception and menopausal hormonal therapy. Norelgestromin may potentially be used in breast cancer treatment due to its inhibitory effect on estrone sulfatase . They convert sulfated steroid precursors to estrogen during pregnancy.
Structured Indications
PharmacodynamicsNorelgestromin is used for contraception and menopausal hormonal therapy transdermally or in combination with ethinyl estradiol as a vaginal ring. Norelgestromin, in combination with ethinyl estradiol inhibits ovulation by suppressing gonadotropins.
Mechanism of actionNorelgestromin inhibits estrone sulfatase, which converts sulfated steroid precursors to estrogen during pregnancy. Norgelgestromin/ethinylestradiol suppresses follicular development, induces changes to the endometrium, which decreases chances of implantation and thickens the cervical mucus, impeding sperm swimming into the uterus. It also has similar agonisting binding affinities as its parent compound, Norgestimate, for progesterone and estrogen receptors.
TargetKindPharmacological actionActionsOrganismUniProt ID
Progesterone receptorProteinyes
agonist
HumanP06401 details
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organismsNot Available
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
Interactions
Drug Interactions
DrugInteractionDrug group
AcenocoumarolNorelgestromin may decrease the anticoagulant activities of Acenocoumarol.Approved
AcitretinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Acitretin.Approved
AdapaleneThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Adapalene.Approved
AlitretinoinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Alitretinoin.Approved, Investigational
AmobarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Amobarbital.Approved, Illicit
AprepitantThe serum concentration of Norelgestromin can be decreased when it is combined with Aprepitant.Approved, Investigational
ArtemetherThe serum concentration of Norelgestromin can be decreased when it is combined with Artemether.Approved
AtazanavirThe serum concentration of Norelgestromin can be increased when it is combined with Atazanavir.Approved, Investigational
BarbexacloneThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Barbexaclone.Experimental
BarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Barbital.Illicit
BexaroteneThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Bexarotene.Approved, Investigational
BexaroteneThe serum concentration of Norelgestromin can be decreased when it is combined with Bexarotene.Approved, Investigational
BoceprevirThe serum concentration of Norelgestromin can be increased when it is combined with Boceprevir.Approved
BosentanThe serum concentration of Norelgestromin can be decreased when it is combined with Bosentan.Approved, Investigational
CarbamazepineThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Carbamazepine.Approved, Investigational
CholestyramineThe serum concentration of Norelgestromin can be decreased when it is combined with Cholestyramine.Approved
ClobazamThe serum concentration of Norelgestromin can be decreased when it is combined with Clobazam.Approved, Illicit
CobicistatThe serum concentration of Norelgestromin can be increased when it is combined with Cobicistat.Approved
ColesevelamThe serum concentration of Norelgestromin can be decreased when it is combined with Colesevelam.Approved
ColestipolThe serum concentration of Norelgestromin can be decreased when it is combined with Colestipol.Approved
DabrafenibThe serum concentration of Norelgestromin can be decreased when it is combined with Dabrafenib.Approved
DarunavirThe serum concentration of Norelgestromin can be decreased when it is combined with Darunavir.Approved
DicoumarolNorelgestromin may decrease the anticoagulant activities of Dicoumarol.Approved
EfavirenzThe serum concentration of Norelgestromin can be decreased when it is combined with Efavirenz.Approved, Investigational
Eslicarbazepine acetateThe serum concentration of Norelgestromin can be decreased when it is combined with Eslicarbazepine acetate.Approved
Ethyl biscoumacetateNorelgestromin may decrease the anticoagulant activities of Ethyl biscoumacetate.Withdrawn
ExenatideThe serum concentration of Norelgestromin can be decreased when it is combined with Exenatide.Approved, Investigational
FelbamateThe serum concentration of Norelgestromin can be decreased when it is combined with Felbamate.Approved
FlibanserinThe serum concentration of Flibanserin can be increased when it is combined with Norelgestromin.Approved
FluindioneNorelgestromin may decrease the anticoagulant activities of Fluindione.Investigational
FosamprenavirThe serum concentration of the active metabolites of Fosamprenavir can be reduced when Fosamprenavir is used in combination with Norelgestromin resulting in a loss in efficacy.Approved
FosaprepitantThe serum concentration of Norelgestromin can be decreased when it is combined with Fosaprepitant.Approved
FosphenytoinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Fosphenytoin.Approved
GriseofulvinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Griseofulvin.Approved, Vet Approved
HexobarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Hexobarbital.Approved
IsotretinoinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Isotretinoin.Approved
LamotrigineThe serum concentration of Norelgestromin can be decreased when it is combined with Lamotrigine.Approved, Investigational
LopinavirThe serum concentration of Norelgestromin can be decreased when it is combined with Lopinavir.Approved
LumacaftorThe serum concentration of Norelgestromin can be decreased when it is combined with Lumacaftor.Approved
MethohexitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Methohexital.Approved
MethylphenobarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Methylphenobarbital.Approved
MetreleptinThe serum concentration of Norelgestromin can be decreased when it is combined with Metreleptin.Approved
MifepristoneThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Mifepristone.Approved, Investigational
Mycophenolic acidThe serum concentration of Norelgestromin can be decreased when it is combined with Mycophenolic acid.Approved
NelfinavirThe serum concentration of Norelgestromin can be decreased when it is combined with Nelfinavir.Approved
NevirapineThe serum concentration of Norelgestromin can be decreased when it is combined with Nevirapine.Approved
OxcarbazepineThe serum concentration of Norelgestromin can be decreased when it is combined with Oxcarbazepine.Approved
PentobarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Pentobarbital.Approved, Vet Approved
PerampanelThe serum concentration of Norelgestromin can be decreased when it is combined with Perampanel.Approved
PhenindioneNorelgestromin may decrease the anticoagulant activities of Phenindione.Approved
PhenobarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Phenobarbital.Approved
PhenprocoumonNorelgestromin may decrease the anticoagulant activities of Phenprocoumon.Approved
PhenytoinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Phenytoin.Approved, Vet Approved
PrimidoneThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Primidone.Approved, Vet Approved
PrucaloprideThe serum concentration of Norelgestromin can be decreased when it is combined with Prucalopride.Approved
RifabutinThe serum concentration of Norelgestromin can be decreased when it is combined with Rifabutin.Approved
RifampicinThe serum concentration of Norelgestromin can be decreased when it is combined with Rifampicin.Approved
RifapentineThe serum concentration of Norelgestromin can be decreased when it is combined with Rifapentine.Approved
SaquinavirThe serum concentration of Norelgestromin can be decreased when it is combined with Saquinavir.Approved, Investigational
SecobarbitalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Secobarbital.Approved, Vet Approved
SelegilineThe serum concentration of Selegiline can be increased when it is combined with Norelgestromin.Approved, Investigational, Vet Approved
St. John's WortThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with St. John's Wort.Nutraceutical
SugammadexThe serum concentration of Norelgestromin can be decreased when it is combined with Sugammadex.Approved
TelaprevirThe serum concentration of Norelgestromin can be decreased when it is combined with Telaprevir.Approved
ThalidomideNorelgestromin may increase the thrombogenic activities of Thalidomide.Approved, Investigational, Withdrawn
ThiamylalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Thiamylal.Approved, Vet Approved
ThiopentalThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Thiopental.Approved, Vet Approved
TipranavirThe serum concentration of Norelgestromin can be increased when it is combined with Tipranavir.Approved, Investigational
TopiramateThe serum concentration of Norelgestromin can be decreased when it is combined with Topiramate.Approved
Tranexamic AcidNorelgestromin may increase the thrombogenic activities of Tranexamic Acid.Approved
TretinoinThe therapeutic efficacy of Norelgestromin can be decreased when used in combination with Tretinoin.Approved, Investigational, Nutraceutical
VoriconazoleThe serum concentration of Norelgestromin can be increased when it is combined with Voriconazole.Approved, Investigational
WarfarinNorelgestromin may decrease the anticoagulant activities of Warfarin.Approved
Food InteractionsNot Available
References
Synthesis Reference

Zoltan Tuba, Sandor Maho, Gyorgy Keseru, Jozsef Kozma, Janos Horvath, Gabor Balogh, “Process of making isomers of norelgestromin and methods using the same.” U.S. Patent US20050032764, issued February 10, 2005.

US20050032764
General References
  1. Goa KL, Warner GT, Easthope SE: Transdermal ethinylestradiol/norelgestromin: a review of its use in hormonal contraception. Treat Endocrinol. 2003;2(3):191-206. [PubMed:15966567 ]
  2. Henzl MR: Norgestimate. From the laboratory to three clinical indications. J Reprod Med. 2001 Jul;46(7):647-61. [PubMed:11499185 ]
  3. Abrams LS, Skee DM, Wong FA, Anderson NJ, Leese PT: Pharmacokinetics of norelgestromin and ethinyl estradiol from two consecutive contraceptive patches. J Clin Pharmacol. 2001 Nov;41(11):1232-7. [PubMed:11697756 ]
External Links
ATC CodesG03AA13
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9958
Blood Brain Barrier+0.9436
Caco-2 permeable+0.5219
P-glycoprotein substrateSubstrate0.6364
P-glycoprotein inhibitor INon-inhibitor0.5618
P-glycoprotein inhibitor IINon-inhibitor0.8348
Renal organic cation transporterNon-inhibitor0.6802
CYP450 2C9 substrateNon-substrate0.7663
CYP450 2D6 substrateNon-substrate0.8257
CYP450 3A4 substrateSubstrate0.6965
CYP450 1A2 substrateNon-inhibitor0.7341
CYP450 2C9 inhibitorNon-inhibitor0.6798
CYP450 2D6 inhibitorNon-inhibitor0.8528
CYP450 2C19 inhibitorNon-inhibitor0.529
CYP450 3A4 inhibitorNon-inhibitor0.5718
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.846
Ames testNon AMES toxic0.5162
CarcinogenicityNon-carcinogens0.8087
BiodegradationNot ready biodegradable0.9948
Rat acute toxicity2.4050 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7294
hERG inhibition (predictor II)Non-inhibitor0.7284
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage forms
FormRouteStrength
Patch, extended releaseTransdermal
PatchTransdermal
PricesNot Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5876746 No1995-11-202015-11-20Us
Properties
StateSolid
Experimental PropertiesNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.00605 mg/mLALOGPS
logP3.18ALOGPS
logP3.67ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)11.47ChemAxon
pKa (Strongest Basic)3.12ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area52.82 Å2ChemAxon
Rotatable Bond Count1ChemAxon
Refractivity95.85 m3·mol-1ChemAxon
Polarizability38.4 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as estrane steroids. These are steroids with a structure based on the estrane skeleton.
KingdomOrganic compounds
Super ClassLipids and lipid-like molecules
ClassSteroids and steroid derivatives
Sub ClassEstrane steroids
Direct ParentEstrane steroids
Alternative Parents
Substituents
  • Estrane-skeleton
  • Hydroxysteroid
  • 17-hydroxysteroid
  • Delta-4-steroid
  • Ynone
  • Cyclic alcohol
  • Tertiary alcohol
  • Acetylide
  • Oxime
  • Organonitrogen compound
  • Hydrocarbon derivative
  • Alcohol
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organooxygen compound
  • Aliphatic homopolycyclic compound
Molecular FrameworkAliphatic homopolycyclic compounds
External DescriptorsNot Available

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 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 ...
Gene Name:
PGR
Uniprot ID:
P06401
Molecular Weight:
98979.96 Da
References
  1. Pasqualini JR: Breast cancer and steroid metabolizing enzymes: the role of progestogens. Maturitas. 2009 Dec;65 Suppl 1:S17-21. doi: 10.1016/j.maturitas.2009.11.006. Epub 2009 Dec 3. [PubMed:19962254 ]
  2. London RS, Chapdelaine A, Upmalis D, Olson W, Smith J: Comparative contraceptive efficacy and mechanism of action of the norgestimate-containing triphasic oral contraceptive. Acta Obstet Gynecol Scand Suppl. 1992;156:9-14. [PubMed:1324557 ]
  3. Graziottin A: A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65. [PubMed:17107221 ]
  4. Kuhnz W, Fritzemeier KH, Hegele-Hartung C, Krattenmacher R: Comparative progestational activity of norgestimate, levonorgestrel-oxime and levonorgestrel in the rat and binding of these compounds to the progesterone receptor. Contraception. 1995 Feb;51(2):131-9. [PubMed:7750291 ]
  5. Juchem M, Pollow K, Elger W, Hoffmann G, Mobus V: Receptor binding of norgestimate--a new orally active synthetic progestational compound. Contraception. 1993 Mar;47(3):283-94. [PubMed:8384965 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sulfuric ester hydrolase activity
Specific Function:
Conversion of sulfated steroid precursors to estrogens during pregnancy.
Gene Name:
STS
Uniprot ID:
P08842
Molecular Weight:
65491.72 Da
References
  1. Pasqualini JR, Chetrite GS: Recent insight on the control of enzymes involved in estrogen formation and transformation in human breast cancer. J Steroid Biochem Mol Biol. 2005 Feb;93(2-5):221-36. [PubMed:15860265 ]
  2. Pasqualini JR, Caubel P, Friedman AJ, Philippe JC, Chetrite GS: Norelgestromin as selective estrogen enzyme modulator in human breast cancer cell lines. Effect on sulfatase activity in comparison to medroxyprogesterone acetate. J Steroid Biochem Mol Biol. 2003 Feb;84(2-3):193-8. [PubMed:12711003 ]
  3. Pasqualini JR: The selective estrogen enzyme modulators in breast cancer: a review. Biochim Biophys Acta. 2004 Jun 7;1654(2):123-43. [PubMed:15172700 ]
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Drug created on May 16, 2010 11:47 / Updated on December 07, 2016 02:38