Identification

Logo pink
Are you a
new drug developer?
Contact us to learn more about our customized products and solutions.
Logo pink
Stay in the know!
As part of our commitment to providing the most up-to-date drug information, we will be releasing #DrugBankUpdates with our newly added curated drug pages.
#DrugBankUpdates
Name
Norelgestromin
Accession Number
DB06713
Type
Small Molecule
Groups
Approved, Investigational
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
  • Norelgestromin
  • Norelgestromina
  • Norplant 3-oxime
External IDs
BRN 4202099 / RWJ 10553
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
EvraNorelgestromin (200 mcg) + Ethinylestradiol (35 mcg)Patch, extended releaseTransdermalJanssen Pharmaceuticals2003-12-24Not applicableCanada
Evra -(6/0.75)Norelgestromin (6 mg) + Ethinylestradiol (0.75 mg)Patch, extended releaseTransdermalJanssen Pharmaceuticals2002-10-242006-02-22Canada
Ortho EvraNorelgestromin (150 ug/1d) + Ethinylestradiol (35 ug/1d)Patch, extended releaseTransdermalJanssen Pharmaceuticals2001-11-202018-07-12Us
Ortho EvraNorelgestromin (6 mg/7d) + Ethinylestradiol (0.75 mg/7d)Patch, extended releaseTransdermalOrtho-McNeil-Janssen Pharmaceutical, Inc.2001-11-202012-07-31Us
Ortho EvraNorelgestromin (6 mg/7[USP'U]) + Ethinylestradiol (0.75 mg/7[USP'U])Patch, extended releaseTransdermalPhysicians Total Care, Inc.2002-09-132011-02-28Us
XulaneNorelgestromin (150 ug/1d) + Ethinylestradiol (35 ug/1d)PatchTransdermalA-S Medication Solutions2014-04-16Not applicableUs
XulaneNorelgestromin (150 ug/1d) + Ethinylestradiol (35 ug/1d)PatchTransdermalMylan Pharmaceuticals Inc.2014-04-16Not applicableUs
Categories
UNII
R0TAY3X631
CAS number
53016-31-2
Weight
Average: 327.468
Monoisotopic: 327.219829178
Chemical Formula
C21H29NO2
InChI Key
ISHXLNHNDMZNMC-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

Indication

Norelgestromin 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.

Associated Conditions
Associated Therapies
Pharmacodynamics

Norelgestromin 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 action

Norelgestromin 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.

TargetActionsOrganism
AProgesterone receptor
agonist
Humans
USerum albuminNot AvailableHumans
UAndrogen receptor
partial agonist
Humans
Additional Data Available
Adverse Effects

Comprehensive structured data on known drug adverse effects with statistical prevalence. MedDRA and ICD10 ids are provided for adverse effect conditions and symptoms.

Learn more
Additional Data Available
Contraindications

Structured data covering drug contraindications. Each contraindication describes a scenario in which the drug is not to be used. Includes restrictions on co-administration, contraindicated populations, and more.

Learn more
Additional Data Available
Blackbox Warnings

Structured data representing warnings from the black box section of drug labels. These warnings cover important and dangerous risks, contraindications, or adverse effects.

Learn more
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
(R)-warfarinNorelgestromin may decrease the anticoagulant activities of (R)-warfarin.
(S)-WarfarinNorelgestromin may decrease the anticoagulant activities of (S)-Warfarin.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be decreased when used in combination with Norelgestromin.
7-NitroindazoleThe metabolism of Norelgestromin can be increased when combined with 7-Nitroindazole.
AbciximabNorelgestromin may decrease the anticoagulant activities of Abciximab.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be decreased when used in combination with Norelgestromin.
AcetaminophenThe metabolism of Norelgestromin can be increased when combined with Acetaminophen.
AcetazolamideThe metabolism of Norelgestromin can be increased when combined with Acetazolamide.
AcetohexamideThe therapeutic efficacy of Acetohexamide can be decreased when used in combination with Norelgestromin.
Acetylsalicylic acidNorelgestromin may decrease the anticoagulant activities of Acetylsalicylic acid.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

    Learn more
  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

    Learn more
  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

    Learn more
  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

    Learn more
Food Interactions
Not 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
KEGG Drug
D05205
PubChem Compound
62930
PubChem Substance
99443265
ChemSpider
56648
ChEBI
135398
ChEMBL
CHEMBL1200807
Wikipedia
Norelgestromin
ATC Codes
G03AA13 — Norelgestromin and ethinylestradiol

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedHealth Services ResearchFemale Contraception1
1CompletedTreatmentContraception / Female Contraception2
1CompletedTreatmentHealthy Volunteers1
1RecruitingOtherHealthy Volunteers1
2CompletedPreventionHuman Immunodeficiency Virus (HIV) Infections / Pregnancy1
2CompletedTreatmentMetrorrhagia1
2Unknown StatusTreatmentContraception1
3CompletedPreventionContraception1
3CompletedTreatmentContraception1
3CompletedTreatmentContraception / Female Contraception2
4Active Not RecruitingNot AvailableContraception1
4CompletedBasic ScienceBone; Disorder, Development and Growth1
4CompletedOtherHealthy Volunteers1
4CompletedTreatmentContraception1
4CompletedTreatmentContraception / Female Contraception1
4CompletedTreatmentFemale Contraception1
Not AvailableCompletedNot AvailableContraception / Female Contraception1
Not AvailableCompletedTreatmentContraception1
Not AvailableCompletedTreatmentThrombosis, Venous1
Not AvailableWithdrawnTreatmentMenstrual Cramps / Menstruation Disorders / Menstruation Disturbances1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Patch, extended releaseTransdermal
PatchTransdermal
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5876746No1999-03-022015-11-20Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
Not 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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
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)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
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 estrane steroids. These are steroids with a structure based on the estrane skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Estrane steroids
Direct Parent
Estrane steroids
Alternative Parents
17-hydroxysteroids / Delta-4-steroids / Ynones / Tertiary alcohols / Ketoximes / Cyclic alcohols and derivatives / Acetylides / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Estrane-skeleton / Hydroxysteroid / 17-hydroxysteroid / Delta-4-steroid / Ynone / Cyclic alcohol / Ketoxime / Tertiary alcohol / Oxime / Acetylide
Molecular Framework
Aliphatic homopolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
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. 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]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Hammond GL, Abrams LS, Creasy GW, Natarajan J, Allen JG, Siiteri PK: Serum distribution of the major metabolites of norgestimate in relation to its pharmacological properties. Contraception. 2003 Feb;67(2):93-9. [PubMed:12586319]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Partial agonist
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 ...
Gene Name
AR
Uniprot ID
P10275
Uniprot Name
Androgen receptor
Molecular Weight
98987.9 Da
References
  1. Prifti S, Lelle I, Strowitzki T, Rabe T: Induction of androgen receptor activity by norgestimate and norelgestromin in MDA-MB 231 breast cancer cells. Gynecol Endocrinol. 2004 Jul;19(1):18-21. [PubMed:15625768]

Enzymes

Kind
Protein
Organism
Humans
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
Uniprot Name
Steryl-sulfatase
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]
Kind
Protein
Organism
Humans
Pharmacological action
No
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

Drug created on May 16, 2010 11:47 / Updated on November 02, 2019 01:59