U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C29H35NO2
Molecular Weight 429.5948
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MIFEPRISTONE

SMILES

CC#C[C@@]1(CC[C@@]2([H])[C@]3([H])CCC4=CC(=O)CCC4=C3[C@]([H])(C[C@@]21C)c5ccc(cc5)N(C)C)O

InChI

InChIKey=VKHAHZOOUSRJNA-GCNJZUOMSA-N
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

HIDE SMILES / InChI

Molecular Formula C29H35NO2
Molecular Weight 429.5948
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 5 / 5
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/cdi/mifepristone.html

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. 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. Mifepristone is used 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 and are not candidates for surgery or have had unsuccessful surgery.

CNS Activity

Curator's Comment:: mifepristone does cross the blood-brain barrier

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.35 nM [IC50]
0.8 nM [IC50]
5.0 nM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
MIFEPREX

Approved Use

MIFEPREX is indicated, in a regimen with misoprostol, for the medical termination of intrauterine pregnancy through 70 days gestation.

Launch Date

9.7001282E11
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1.77 mg/L
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIFEPRISTONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
25.8 mg × h/L
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIFEPRISTONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
18 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
MIFEPRISTONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: UNKNOWN
OverviewDrug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
inconclusive [IC50 >10 uM]
inconclusive [IC50 >10 uM]
no
no
yes [IC50 1 uM]
yes [IC50 1.8 uM]
yes (co-administration study)
Comment: The sponsor reported that Cmax values of digoxin were increased when digoxin was administered with the first dose (ratio, 1.68, CI, 1.54-1.84) and the last dose of mifepristone (ratio, 1.64, CI, 1.50-1.79).
Page: 32.0
yes [IC50 3 uM]
yes [IC50 3 uM]
yes (co-administration study)
Comment: The first and last multiple doses of mifepristone 1200 mg/day for 7 days produced 2.67- fold and 3.57 fold increase, respectively, in fluvastatin AUC0-24.
Page: 33.0
yes [IC50 3.5 uM]
yes (co-administration study)
Comment: The first and last multiple doses of mifepristone 1200 mg/day for 7 days produced 2.67- fold and 3.57 fold increase, respectively, in fluvastatin AUC0-24.
Page: 33.0
yes [IC50 4.3 uM]
yes [IC50 5.6 uM]
yes [IC50 6.7 uM]
yes (co-administration study)
Comment: The first and last multiple doses of mifepristone 1200 mg/day for 7 days produced 2.67- fold and 3.57 fold increase, respectively, in fluvastatin AUC0-24.
Page: 33.0
yes [IC50 67 uM]
yes [IC50 70 uM]
yes [IC50 8.5 uM]
yes [IC50 8.5 uM]
yes [IC50 8.6 uM]
yes (co-administration study)
Comment: The first and last multiple doses of mifepristone 1200 mg/day for 7 days produced 2.67- fold and 3.57 fold increase, respectively, in fluvastatin AUC0-24.
Page: 11.0
yes [IC50 8.6 uM]
yes (co-administration study)
Comment: AUC0-72 hr of alprazolam and 4-OH alprazolam following 1 mg of alprazolam increased 80% (n=16) and 76% (n=16) , respectively with concomitant administration of multiple doses of 1200 mg/day mifepristone for 10 days compared to those following 1 mg of alprazolam alone.
Page: 33.0
yes [IC50 8.7 uM]
yes (co-administration study)
Comment: AUC0-72 hr of alprazolam and 4-OH alprazolam following 1 mg of alprazolam increased 80% (n=16) and 76% (n=16) , respectively with concomitant administration of multiple doses of 1200 mg/day mifepristone for 10 days compared to those following 1 mg of alprazolam alone.
Page: 33.0
yes [IC50 9.1 uM]
yes [IC50 >10 uM]
yes (co-administration study)
Comment: The first and last multiple doses of mifepristone 1200 mg/day for 7 days produced 2.67- fold and 3.57 fold increase, respectively, in fluvastatin AUC0-24.
Page: 11.0
yes [IC50 >50 uM]
yes [Ki 4.7 uM]
yes (co-administration study)
Comment: AUC0-72 hr of alprazolam and 4-OH alprazolam following 1 mg of alprazolam increased 80% (n=16) and 76% (n=16) , respectively with concomitant administration of multiple doses of 1200 mg/day mifepristone for 10 days compared to those following 1 mg of alprazolam alone.
Page: 25.0
yes
yes
yes
Drug as victimTox targets
PubMed

PubMed

TitleDatePubMed
[Cardiocirculatory arrest after administration of combined mifepristone (Mifegyne) and sulprostone (Nalador) for induced abortion. Possible role of coronary vasospasm].
1992 Jan
Role of cysteines 640, 656, and 661 in steroid binding to rat glucocorticoid receptors.
1992 Jun 5
Hormone activation of baculovirus expressed progesterone receptors.
1992 Mar 15
Peroxisome proliferator-activated receptor alpha agonists increase nitric oxide synthase expression in vascular endothelial cells.
2004 Apr
Mifepristone induces growth arrest, caspase activation, and apoptosis of estrogen receptor-expressing, antiestrogen-resistant breast cancer cells.
2004 Aug 1
Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.
2004 Aug 12
Glucocorticoid receptor antagonists: new tools to investigate disorders characterized by cortisol hypersecretion.
2004 Dec
Differential signal transduction of progesterone and medroxyprogesterone acetate in human endothelial cells.
2004 Dec
Tibolone and its metabolites induce antimitogenesis in human coronary artery smooth muscle cells: role of estrogen, progesterone, and androgen receptors.
2004 Feb
The unusual binding properties of the third distinct teleost estrogen receptor subtype ERbetaa are accompanied by highly conserved amino acid changes in the ligand binding domain.
2004 Jun
Dexamethasone suppresses antigen-induced activation of phosphatidylinositol 3-kinase and downstream responses in mast cells.
2004 Jun 15
Stress enables synaptic depression in CA1 synapses by acute and chronic morphine: possible mechanisms for corticosterone on opiate addiction.
2004 Mar 10
[Pharmacokinetics of mifepristone and kinetics of chorionic gonadotropin beta-subunit (beta-HCG) and progesterone in plasma of pregnant women during pharmacological interruption of early pregnancy].
2004 Mar-Apr
Short-chain fatty acids enhance nuclear receptor activity through mitogen-activated protein kinase activation and histone deacetylase inhibition.
2004 May 4
Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor.
2004 Nov
Glucocorticoid receptor involvement in pair bonding in female prairie voles: the effects of acute blockade and interactions with central dopamine reward systems.
2005
Characterization of a critical region in the hormone binding domain of sperm progesterone receptor.
2005 Apr
Lack of synergy between estrogen and progesterone on local IGF-I, IGFBP-3 and IGFBP-2 secretion by both hormone-dependent and hormone-independent breast cancer explants in vitro. Effect of tamoxifen and mifepristone (RU 486).
2005 Apr
Serum- and glucocorticoid-inducible kinase 1 (SGK1) mediates glucocorticoid-induced inhibition of insulin secretion.
2005 Apr
Conditional regulation of the human CYP4X1 and CYP4Z1 genes.
2005 Apr 15
Behavioral stress enhances hippocampal CA1 long-term depression through the blockade of the glutamate uptake.
2005 Apr 27
Induction of thymocyte apoptosis by systemic administration of concanavalin A in mice: role of TNF-alpha, IFN-gamma and glucocorticoids.
2005 Aug
Modulation of cytokine production by dydrogesterone in lymphocytes from women with recurrent miscarriage.
2005 Aug
Monoamine oxidase-A is a major target gene for glucocorticoids in human skeletal muscle cells.
2005 Aug
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.
2005 Aug
Proliferation of endothelial and tumor epithelial cells by progestin-induced vascular endothelial growth factor from human breast cancer cells: paracrine and autocrine effects.
2005 Aug
CAR and PXR: xenosensors of endocrine disrupters?
2005 Aug 15
Progestin activation of nongenomic pathways via cross talk of progesterone receptor with estrogen receptor beta induces proliferation of endometrial stromal cells.
2005 Dec
p53-dependent inhibition of progestin-induced VEGF expression in human breast cancer cells.
2005 Feb
Progesterone increases tissue factor gene expression, procoagulant activity, and invasion in the breast cancer cell line ZR-75-1.
2005 Feb
The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice.
2005 Feb
Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids.
2005 Feb 1
Novel progestogenic activity of environmental endocrine disruptors in the upregulation of calbindin-D9k in an immature mouse model.
2005 Jan
High volume bioassays to assess CYP3A4-mediated drug interactions: induction and inhibition in a single cell line.
2005 Jan
A comparison of in vitro and in vivo EDSTAC test battery results for detecting antiandrogenic activity.
2005 Jan 1
Characterization of thymic atrophy and the mechanism of thymocyte depletion after in vivo exposure to a mixture of herbicides.
2005 Jan 22
Effect of mifepristone on proliferation and apoptosis of Ishikawa endometrial adenocarcinoma cells.
2005 Jul
The effects of cortisol administration on social status and brain monoaminergic activity in rainbow trout Oncorhynchus mykiss.
2005 Jul
Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol--United States and Canada, 2001-2005.
2005 Jul 29
Progesterone induces the fibulin-1 expression in human endometrial stromal cells.
2005 Jun
Ligand-selective targeting of the glucocorticoid receptor to nuclear subdomains is associated with decreased receptor mobility.
2005 Jun
Inhibition of tristetraprolin expression by dexamethasone in activated macrophages.
2005 Mar 1
15-Hydroxyprostaglandin dehydrogenase can be induced by dexamethasone and other glucocorticoids at the therapeutic level in A549 human lung adenocarcinoma cells.
2005 Mar 1
Identification of ATF-3, caveolin-1, DLC-1, and NM23-H2 as putative antitumorigenic, progesterone-regulated genes for ovarian cancer cells by gene profiling.
2005 Mar 3
Role of activation function domain-1, DNA binding, and coactivator GRIP1 in the expression of partial agonist activity of glucocorticoid receptor-antagonist complexes.
2005 Mar 8
G-CSF, but not corticosterone, mediates circulating neutrophilia induced by febrile-range hyperthermia.
2005 May
Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications.
2005 May-Jun
Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.
2005 Nov
Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii.
2005 Sep
Aldosterone induces angiotensin converting enzyme gene expression via a JAK2-dependent pathway in rat endothelial cells.
2005 Sep
Patents

Sample Use Guides

Usual Adult Dose for Abortion -Day One: 200 mg mifepristone (MIFEPREX) orally as a single dose -Day Two or Three: 800 mcg misoprostol buccally 24 to 48 hours after the first dose of mifepristone (Two 200 mcg misoprostol tablets should be placed in each cheek pouch [the area between the cheek and gums] for 30 minutes and then swallow any remnants with water or another liquid).
Route of Administration: Oral
Exposure to a low concentration (0.5uM) of mifepristone during the receptive period successfully inhibits human embryo implantation process in vitro.
Substance Class Chemical
Created
by admin
on Fri Jun 25 22:00:24 UTC 2021
Edited
by admin
on Fri Jun 25 22:00:24 UTC 2021
Record UNII
320T6RNW1F
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MIFEPRISTONE
HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
RU 486
Code English
MIFEPRISTONE [JAN]
Common Name English
MIFEPRISTONE [INN]
Common Name English
MIFEGYNE
Common Name English
MIFEPRISTONE [MI]
Common Name English
(11.BETA.,17.BETA.)-11-(4-(DIMETHYLAMINO)PHENYL)-17-HYDROXY-17-(1-PROPYNYL)-ESTRA-4,9-DIEN-3-ONE
Common Name English
11.BETA.-(P-(DIMETHYLAMINO)PHENYL)-17.BETA.-HYDROXY-17-(1-PROPYNYL)ESTRA-4,9-DIEN-3-ONE
Common Name English
RU486
Code English
MIFEPRISTONE [MART.]
Common Name English
NSC-759862
Code English
RU 38486
Code English
MIFEPRISTONE [WHO-DD]
Common Name English
MIFEPRISTONE [USAN]
Common Name English
MIFEPRISTONE [HSDB]
Common Name English
MIFEPRISTONE [VANDF]
Common Name English
MIFEPREX
Brand Name English
RU-486
Code English
MIFEPRISTONE [USP-RS]
Common Name English
KORLYM
Brand Name English
MIFEPRISTONE [ORANGE BOOK]
Common Name English
RU-38486
Code English
Classification Tree Code System Code
NDF-RT N0000000115
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
FDA ORPHAN DRUG 196304
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
WHO-ESSENTIAL MEDICINES LIST 22.1 (MIF/MIS)
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
EU-Orphan Drug EU/3/05/298
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
WHO-ATC G03XB01
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
FDA ORPHAN DRUG 506015
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
LIVERTOX 636
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
NCI_THESAURUS C1891
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
NDF-RT N0000175841
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
WHO-VATC QG03XB01
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
WHO-ATC G03XB51
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
FDA ORPHAN DRUG 239507
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
Code System Code Type Description
WIKIPEDIA
MIFEPRISTONE
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
EVMPD
SUB08956MIG
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
NCI_THESAURUS
C655
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
EPA CompTox
84371-65-3
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
DRUG CENTRAL
1805
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
MERCK INDEX
M7536
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY Merck Index
ChEMBL
CHEMBL1276308
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
USP_CATALOG
1443759
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY USP-RS
IUPHAR
2805
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
LACTMED
Mifepristone
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
INN
5752
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
PUBCHEM
55245
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
DRUG BANK
DB00834
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
MESH
D015735
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
FDA UNII
320T6RNW1F
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
HSDB
6841
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
CAS
84371-65-3
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY
RXCUI
6964
Created by admin on Fri Jun 25 22:00:24 UTC 2021 , Edited by admin on Fri Jun 25 22:00:24 UTC 2021
PRIMARY RxNorm
Related Record Type Details
BINDER->LIGAND
Binding to the latter protein is saturable, and the drug displays nonlinear kinetics with respect to plasma concentration and clearance.
BINDING
TRANSPORTER -> INHIBITOR
TRANSPORTER -> INHIBITOR
METABOLIC ENZYME -> SUBSTRATE
MAJOR
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Tmax PHARMACOKINETIC ORAL ADMINISTRATION

SINGLE DOSE