Banner
targets (2) enzymes (1)
for drugs
Identification
Name Norelgestromin
Accession Number DB06713
Type small molecule
Groups approved
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
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Synonyms Not Available
Salts Not Available
Brand names Not Available
Brand mixtures
Brand Name Ingredients
Ortho Evra Norelgestromin + ethinyl estradiol
Categories
  • Contraceptives
  • Contraceptive Agents, Female
CAS number 53016-31-2
Weight Average: 327.4605
Monoisotopic: 327.219829177
Chemical Formula C21H29NO2
InChI Key InChIKey=ISHXLNHNDMZNMC-JCMHNJIXSA-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/b22-15-
Plain Text
IUPAC Name
15-ethyl-14-ethynyl-5-(hydroxyimino)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadec-6-en-14-ol
SMILES
CCC12CCC3C(CCC4=CC(CCC34)=NO)C1CCC2(O)C#C
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Steroids and Steroid Derivatives
Substructures
  • Steroids and Steroid Derivatives
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alkynes
  • Alcohols and Polyols
  • Imines
  • Cyclohexenes and Derivatives
  • Oximes and Derivatives
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.
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.
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
Pharmacoeconomics
Manufacturers Not Available
Packagers Not Available
Dosage forms Not Available
Prices Not Available
Patents Not Available
Properties
State solid
Melting point Not Available
Experimental Properties Not Available
Predicted Properties
Property Value Source
water solubility ALOGPS
logP 0 ALOGPS
logP 3.67 ChemAxon Molconvert
logS 0 ALOGPS
pKa 17.91 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 52.82 ChemAxon Molconvert
rotatable bond count 1 ChemAxon Molconvert
refractivity 95.85 ChemAxon Molconvert
polarizability 38.53 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference
  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
  2. Henzl MR: Norgestimate. From the laboratory to three clinical indications. J Reprod Med. 2001 Jul;46(7):647-61. Pubmed
  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
External Links
Resource Link
KEGG Drug D05205 Link_out
PubChem Compound 13752005 Link_out
PubChem Substance 99443265 Link_out
Wikipedia http://en.wikipedia.org/wiki/Norelgestromin Link_out
ATC Codes
  • G03AA13
AHFS Codes Not Available
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Artemether Artemether may decrease the effectiveness of norelgestromin by increasing its metabolism via CYP3A4. Consider an alternate non-hormonal means of contraception during artemether therapy.
Bexarotene Bexarotene may decrease the serum concentration of Contraceptives (Progestins). Since bexarotene is teratogenic and can lower serum concentrations of norelgestromin, it is advised that women of childbearing potential use two forms of contraception (including at least one non-hormonal form).
Colesevelam Bile Acid Sequestrants may decrease the serum concentration of Contraceptives (Progestins). Administer oral progestin-containing contraceptives at least 1-4 hours prior to or 4-6 hours after administration of a bile acid sequestrant. Consider alternatives in order to avoid this combination when possible, due to the risk for impaired contraceptive effectiveness.
Food Interactions Not Available
Targets

1. Progesterone receptor

Pharmacological action: yes
Actions: agonist

The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues

Organism class: human
UniProt ID: P06401 Link_out
Gene: PGR Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Henzl MR: Norgestimate. From the laboratory to three clinical indications. J Reprod Med. 2001 Jul;46(7):647-61. Pubmed
  2. Pasqualini JR: Breast cancer and steroid metabolizing enzymes: the role of progestogens. Maturitas. 2009 Dec;65 Suppl 1:S17-21. Epub 2009 Dec 3. Pubmed
  3. 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
  4. Graziottin A: A review of transdermal hormonal contraception : focus on the ethinylestradiol/norelgestromin contraceptive patch. Treat Endocrinol. 2006;5(6):359-65. Pubmed
  5. 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
  6. 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

2. Estrogen receptor

Pharmacological action: yes
Actions: agonist

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

Organism class: human
UniProt ID: P03372 Link_out
Gene: ESR1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Pasqualini JR: Differential effects of progestins on breast tissue enzymes. Maturitas. 2003 Dec 10;46 Suppl 1:S45-54. Pubmed
  2. Juchem M, Pollow K: Binding of oral contraceptive progestogens to serum proteins and cytoplasmic receptor. Am J Obstet Gynecol. 1990 Dec;163(6 Pt 2):2171-83. Pubmed
  3. 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. Pubmed
Enzymes

1. Steryl-sulfatase

Actions: inhibitor

Conversion of sulfated steroid precursors to estrogens during pregnancy

UniProt ID: P08842 Link_out
Gene: STS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Pasqualini JR: The selective estrogen enzyme modulators in breast cancer: a review. Biochim Biophys Acta. 2004 Jun 7;1654(2):123-43. Pubmed
Comments
Drug created on May 16, 2010 11:47 / Updated on February 14, 2012 12:18