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Identification
NameNorelgestromin
Accession NumberDB06713
TypeSmall Molecule
GroupsApproved
Description

Norelgestromin 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
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
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.
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.
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
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 release)transdermal
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
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
Interactions
Drug InteractionsNot Available
Food InteractionsNot 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 August 30, 2016 02:11