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Identification
Name Mifepristone
Accession Number DB00834 (APRD00432)
Type small molecule
Groups approved
Description

A progestational and glucocorticoid hormone antagonist. Its inhibition of progesterone induces bleeding during the luteal phase and in early pregnancy by releasing endogenous prostaglandins from the endometrium or decidua. As a glucocorticoid receptor antagonist, the drug has been used to treat hypercortisolism in patients with nonpituitary cushing syndrome. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Mifepriston
Mifepristona [Spanish]
Mifepristonum [Latin]
RU486
Salts Not Available
Brand names
Name Company
Corlux
Korlym Corcept Therapeutics
Mifegyne
Mifeprex Danco Laboratories
Brand mixtures Not Available
Categories
  • Contraceptives, Oral, Synthetic
  • Menstruation-Inducing Agents
  • Luteolytic Agents
  • Contraceptives, Postcoital, Synthetic
  • Hormone Antagonists
  • Abortifacient Agents, Steroidal
CAS number 84371-65-3
Weight Average: 429.5937
Monoisotopic: 429.266779369
Chemical Formula C29H35NO2
InChI Key InChIKey=VKHAHZOOUSRJNA-GCNJZUOMSA-N
InChI
InChI=1S/C29H35NO2/c1-5-15-29(32)16-14-26-24-12-8-20-17-22(31)11-13-23(20)27(24)25(18-28(26,29)2)19-6-9-21(10-7-19)30(3)4/h6-7,9-10,17,24-26,32H,8,11-14,16,18H2,1-4H3/t24-,25+,26-,28-,29-/m0/s1
Plain Text
IUPAC Name
(10S,11S,14S,15S,17R)-17-[4-(dimethylamino)phenyl]-14-hydroxy-15-methyl-14-(prop-1-yn-1-yl)tetracyclo[8.7.0.0^{2,7}.0^{11,15}]heptadeca-1,6-dien-5-one
SMILES
[H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C1=CC=C(C=C1)N(C)C)C1=C3CCC(=O)C=C3CC[C@@]21[H]
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Benzene and Derivatives
  • Cyclohexenes and Derivatives
  • Anilines
Substructures
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Alkynes
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Alcohols and Polyols
  • Isoprenes
  • Aromatic compounds
  • Cyclohexenes and Derivatives
  • Anilines
  • Ketones
Pharmacology
Indication For the medical termination of intrauterine pregnancy through 49 days' pregnancy. Also indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes mellitus or glucose intolerance.
Pharmacodynamics Mifepristone is a synthetic steroid with antiprogestational effects indicated for the medical termination of intrauterine pregnancy through 49 days' pregnancy. Doses of 1 mg/kg or greater of mifepristone have been shown to antagonize the endometrial and myometrial effects of progesterone in women. During pregnancy, the compound sensitizes the myometrium to the contraction-inducing activity of prostaglandins. Mifepristone also exhibits antiglucocorticoid and weak antiandrogenic activity. The activity of the glucocorticoid dexamethasone in rats was inhibited following doses of 10 to 25 mg/kg of mifepristone. Doses of 4.5 mg/kg or greater in human beings resulted in a compensatory elevation of adrenocorticotropic hormone (ACTH) and cortisol.
Mechanism of action The anti-progestational activity of mifepristone results from competitive interaction with progesterone at progesterone-receptor sites. Based on studies with various oral doses in several animal species (mouse, rat, rabbit and monkey), the compound inhibits the activity of endogenous or exogenous progesterone. The termination of pregnancy results. In the treatment of Cushing's syndrome, Mifepristone blocks the binding of cortisol to its receptor. It does not decrease cortisol production but reduces the effects of excess cortisol, such as high blood sugar levels.
Absorption The absolute bioavailability of a 20 mg oral dose is 69%
Volume of distribution Not Available
Protein binding 98% (bound to plasma proteins, albumin and a 1-acid glycoprotein)
Metabolism Hepatic. Hepatic, by Cytochrome P450 3A4 isoenzyme to the N-monodemethylated metabolite (RU 42 633); RU 42 698, which results from the loss of two methyl groups from position 11 beta; and RU 42 698, which results from terminal hydroxylation of the 17–propynyl chain.
Route of elimination Fecal: 83%; Renal: 9%.
Half life 18 hours
Clearance Not Available
Toxicity Nearly all of the women who receive mifepristone will report adverse reactions, and many can be expected to report more than one such reaction. About 90% of patients report adverse reactions following administration of misoprostol on day three of the treatment procedure. Side effects include more heavy bleeding than a heavy manstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Danco laboratories llc
Packagers
  • Danco Labs LLC
Dosage forms
Form Route Strength
Tablet Oral 200mg
Prices
Unit description Cost Unit
Mifeprex 200 mg tablet 90.0 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 191-196 °C FDA Label
water solubility Poorly soluble FDA Label
logP 4.5 Not Available
Predicted Properties
Property Value Source
water solubility 3.36e-03 g/l ALOGPS
logP 5.33 ALOGPS
logP 5.13 ChemAxon
logS -5.1 ALOGPS
pKa (strongest acidic) 12.87 ChemAxon
pKa (strongest basic) 4.89 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 3 ChemAxon
hydrogen donor count 1 ChemAxon
polar surface area 40.54 ChemAxon
rotatable bond count 3 ChemAxon
refractivity 132.58 ChemAxon
polarizability 50.71 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Fiala C, Gemzel-Danielsson K: Review of medical abortion using mifepristone in combination with a prostaglandin analogue. Contraception. 2006 Jul;74(1):66-86. Epub 2006 May 19. Pubmed
  2. Heikinheimo O, Kekkonen R, Lahteenmaki P: The pharmacokinetics of mifepristone in humans reveal insights into differential mechanisms of antiprogestin action. Contraception. 2003 Dec;68(6):421-6. Pubmed
  3. Chabbert-Buffet N, Meduri G, Bouchard P, Spitz IM: Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005 May-Jun;11(3):293-307. Epub 2005 Mar 24. Pubmed
  4. Spitz IM, Bardin CW, Benton L, Robbins A: Early pregnancy termination with mifepristone and misoprostol in the United States. N Engl J Med. 1998 Apr 30;338(18):1241-7. Pubmed
  5. Piaggio G, von Hertzen H, Heng Z, Bilian X, Cheng L: Meta-analyses of randomized trials comparing different doses of mifepristone in emergency contraception. Contraception. 2003 Dec;68(6):447-52. Pubmed
External Links
Resource Link
KEGG Drug D00585 Link_out
KEGG Compound C07652 Link_out
PubChem Compound 55245 Link_out
PubChem Substance 46505795 Link_out
ChemSpider 49889 Link_out
BindingDB 18627 Link_out
ChEBI 50692 Link_out
ChEMBL 50692 Link_out
Therapeutic Targets Database DAP000090 Link_out
PharmGKB PA450500 Link_out
IUPHAR 2805 Link_out
Guide to Pharmacology 2805 Link_out
HET 486 Link_out
RxList http://www.rxlist.com/cgi/generic3/mifeprist.htm Link_out
Drugs.com http://www.drugs.com/cdi/mifepristone.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Mifepristone Link_out
ATC Codes
  • G03XB01
AHFS Codes Not Available
PDB Entries Not Available
FDA label show (46.5 KB)
MSDS show (57.1 KB)
Interactions
Drug Interactions
Drug Interaction
Dabigatran etexilate May lead to excessive post-abortion bleeding in patients on anticoagulant therapy. Concomitant therapy is contraindicated.
Degarelix Enhance QTc-prolonging effect
Food Interactions Not Available
Targets

1. Progesterone receptor

Pharmacological action: yes
Actions: antagonist

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. Greb RR, Kiesel L, Selbmann AK, Wehrmann M, Hodgen GD, Goodman AL, Wallwiener D: Disparate actions of mifepristone (RU 486) on glands and stroma in the primate endometrium. Hum Reprod. 1999 Jan;14(1):198-206. Pubmed
  2. Sun M, Zhu G, Zhou L: [Effect of mifepristone on the expression of progesterone receptor messenger RNA and protein in uterine leiomyomata] Zhonghua Fu Chan Ke Za Zhi. 1998 Apr;33(4):227-31. Pubmed
  3. Hazra BG, Basu S, Pore VS, Joshi PL, Pal D, Chakrabarti P: Synthesis of 11beta-(4-dimethylaminophenyl)-17beta-hydroxy-17alpha- (3-methyl-1-butynyl)-4, 9-estradien-3-one and 11beta-(4-acetophenyl)- 17beta-hydroxy-17alpha-(3-methyl-1-butynyl)-4, 9-estradien-3-one: two new analogs of mifepristone (RU-486). Steroids. 2000 Mar;65(3):157-62. Pubmed
  4. Gao Y, Cheng L, Liu Y: [Failure of mifepristone induced interruption of pregnancy: point mutation at genetic codon 722 in human progesterone receptor gene] Zhonghua Fu Chan Ke Za Zhi. 1998 Sep;33(9):549-52. Pubmed
  5. Jiang J, Wu R, Wang Z: [Effects of mifepristone on expression of estrogen receptor and progesterone receptor in cultured human eutopic and ectopic endometria] Zhonghua Fu Chan Ke Za Zhi. 2001 Apr;36(4):218-21. Pubmed
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

2. Glucocorticoid receptor

Pharmacological action: yes
Actions: antagonist

Receptor for glucocorticoids (GC). Has a dual mode of action:as a transcription factor that binds to glucocorticoid response elements (GRE) 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

Organism class: human
UniProt ID: P04150 Link_out
Gene: NR3C1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. LeVan TD, Babin EA, Yamamura HI, Bloom JW: Pharmacological characterization of glucocorticoid receptors in primary human bronchial epithelial cells. Biochem Pharmacol. 1999 May 1;57(9):1003-9. Pubmed
  2. Attardi BJ, Burgenson J, Hild SA, Reel JR: In vitro antiprogestational/antiglucocorticoid activity and progestin and glucocorticoid receptor binding of the putative metabolites and synthetic derivatives of CDB-2914, CDB-4124, and mifepristone. J Steroid Biochem Mol Biol. 2004 Mar;88(3):277-88. Pubmed
  3. Aida K, Shi Q, Wang J, VandeBerg JL, McDonald T, Nathanielsz P, Wang XL: The effects of betamethasone (BM) on endothelial nitric oxide synthase (eNOS) expression in adult baboon femoral arterial endothelial cells. J Steroid Biochem Mol Biol. 2004 Aug;91(4-5):219-24. Pubmed
  4. Gu G, Hentunen TA, Nars M, Harkonen PL, Vaananen HK: Estrogen protects primary osteocytes against glucocorticoid-induced apoptosis. Apoptosis. 2005 May;10(3):583-95. Pubmed
  5. de Pablos RM, Villaran RF, Arguelles S, Herrera AJ, Venero JL, Ayala A, Cano J, Machado A: Stress increases vulnerability to inflammation in the rat prefrontal cortex. J Neurosci. 2006 May 24;26(21):5709-19. Pubmed
Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor, inducer

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out
Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 3A5

Actions: substrate, inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P20815 Link_out
Gene: CYP3A5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

3. Cytochrome P450 3A7

Actions: inhibitor

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics

UniProt ID: P24462 Link_out
Gene: CYP3A7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Flockhart DA. Drug Interactions: Cytochrome P450 Drug Interaction Table. Indiana University School of Medicine (2007). Accessed May 28, 2010.
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

4. Cytochrome P450 2D6

Actions: inhibitor

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants

UniProt ID: P10635 Link_out
Gene: CYP2D6 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor, inducer

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Geick A, Eichelbaum M, Burk O: Nuclear receptor response elements mediate induction of intestinal MDR1 by rifampin. J Biol Chem. 2001 May 4;276(18):14581-7. Epub 2001 Jan 31. Pubmed
  2. Lecureur V, Fardel O, Guillouzo A: The antiprogestatin drug RU 486 potentiates doxorubicin cytotoxicity in multidrug resistant cells through inhibition of P-glycoprotein function. FEBS Lett. 1994 Nov 28;355(2):187-91. Pubmed

2. Multidrug resistance-associated protein 1

Actions: inhibitor

May participate directly in the active transport of drugs into subcellular organelles or influence drug distribution indirectly. Confers resistance to anticancer drugs. Transports LTC4. May protect milk against xenobiotics

UniProt ID: P33527 Link_out
Gene: ABCC1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Payen L, Delugin L, Courtois A, Trinquart Y, Guillouzo A, Fardel O: Reversal of MRP-mediated multidrug resistance in human lung cancer cells by the antiprogestatin drug RU486. Biochem Biophys Res Commun. 1999 May 19;258(3):513-8. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19