MIFEPRISTONE

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C29H35NO2
Molecular Weight	429.5937
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

[H][C@@]12CC[C@@](O)(C#CC)[C@@]1(C)C[C@H](C3=CC=C(C=C3)N(C)C)C4=C5CCC(=O)C=C5CC[C@@]24[H]

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	429.5937
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	5 / 5
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.drugbank.ca/drugs/DB00834
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Progesterone receptor 61 Target ID: CHEMBL208 Sources: http://www.drugbank.ca/drugs/DB00834	Antagonist 2778	0.35 nM [IC50]
Glucocorticoid receptor 172 Target ID: CHEMBL2034 Sources: http://www.drugbank.ca/drugs/DB00834	Antagonist 2778	0.8 nM [IC50]
Androgen Receptor 167 Target ID: CHEMBL1871 Sources: https://www.ncbi.nlm.nih.gov/pubmed/8627601	Antagonist 2778	5.0 nM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Intrauterine pregnancy through 70 days gestation 1 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf	Curative		Approved 8429	MIFEPREX Approved Use MIFEPREX is indicated, in a regimen with misoprostol, for the medical termination of intrauterine pregnancy through 70 days gestation. Launch Date 2000

C_max

Value	Dose	Co-administered	Analyte	Population
1.77 mg/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf	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

Value	Dose	Co-administered	Analyte	Population
25.8 mg × h/L DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf	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

T_1/2

Value	Dose	Co-administered	Analyte	Population
18 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020687s020lbl.pdf	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

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inhibitor 1587	inhibitor 1767	inhibitor 1852	inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 214 CYP2C8 911 CYP2B6 810 CYP1A2 1524 CYP2A6 707 CYP2C19 1478 CYP2E1 882 P-gp 1461 BCRP 699 OATP1B1 788 OATP1B3 706 OATP2B1 123 OCT1 512 NTCP 34 BSEP 402	CYP2B 10 CYP2C 11 P-gp 1537 BCRP 561	CYP3A 129

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=26 Page: 26.0	inconclusive [IC50 >10 uM]
CYP2D6 1891	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=26 Page: 26.0	inconclusive [IC50 >10 uM]
CYP1A2 1692	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=26 Page: 26.0	no
CYP2E1 970	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=26 Page: 26.0	no
OATP1B3 715	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 1 uM]
P-gp 1650	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=32 Page: 32.0	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). Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=32 Page: 32.0
BSEP 403	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=102 Page: 102.0	yes [IC50 3 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 3 uM]	RU 42698 1	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 3.5 uM]	RU 42633 1	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
OATP2B1 126	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 4.3 uM]
BCRP 773	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=32 Page: 32.0	yes [IC50 5.6 uM]
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 6.7 uM]	RU 42848 1	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
OCT1 543	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 67 uM]
NTCP 35	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 70 uM]
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 8.5 uM]	RU 42698 1
CYP2C19 1553	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 8.5 uM]	RU 42698 1
CYP2C8 965	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=11 Page: 11.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=11 Page: 11.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 8.6 uM]	RU 42633 1	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0	yes [IC50 8.7 uM]	RU 42698 1	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=33 Page: 33.0
OATP1B1 803	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=34 Page: 34.0	yes [IC50 9.1 uM]
CYP2C9 1819	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=11 Page: 11.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=11 Page: 11.0
CYP2A6 739	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=26 Page: 26.0	yes [IC50 >50 uM]
CYP3A4 1925	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=25 Page: 25.0	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. Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=25 Page: 25.0
CYP2B6 1001	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=11 Page: 11.0	yes
CYP3A 298	inducer 1573 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=26 Page: 26.0	yes
CYP3A 298	inhibitor 3277 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=10 Page: 10.0	yes

Drug as victim

Target	Modality	Activity
CYP2B 10	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=25 Page: 25.0	minor
CYP2C 11	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=25 Page: 25.0	minor
BCRP 561	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes
CYP3A4 1737	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202107s008lbl.pdf#page=15 Page: 15.0	yes
P-gp 1537	substrate 3367 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000ClinPharmR.pdf#page=10 Page: 10.0	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=18 Page: 18.0
hERG 1647	inhibitor 1626 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/202107Orig1s000PharmR.pdf#page=18 Page: 18.0		RU42848 1

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:50692	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:50692
ChemicalBook	CB6351940	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB6351940
MolPort	MolPort-003-849-222	https://www.molport.com/shop/molecule-link/MolPort-003-849-222
Selleck Chemicals	Mifepristone(Mifeprex)	http://www.selleckchem.com/products/Mifepristone(Mifeprex).html
ZINC	ZINC000003831128	http://zinc15.docking.org/substances/ZINC000003831128
eMolecules	29563088	https://www.emolecules.com/cgi-bin/more?vid=29563088
eMolecules	30154688	https://www.emolecules.com/cgi-bin/more?vid=30154688
eMolecules	592261	https://www.emolecules.com/cgi-bin/more?vid=592261

PubMed

Title	Date	PubMed
[Study of histopathology of endometrium following termination of early pregnancy using mifepristone].	1999 May	11326931
Timing of pain and bleeding after mifepristone-induced abortion.	2000 Dec	11239617
Glucocorticoids act within minutes to inhibit recruitment of signalling factors to activated EGF receptors through a receptor-dependent, transcription-independent mechanism.	2000 May	10807665
Comparison of abortions induced by methotrexate or mifepristone followed by misoprostol.	2002 May	11978292
Molecular basis of rifampicin-induced inhibition of anti-CD95-induced apoptosis of peripheral blood T lymphocytes: the role of CD95 ligand and FLIPs.	2003 Jan	12645856
Glucocorticoids play a fundamental role in protecting the brain during innate immune response.	2003 Jul 2	12843254
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) stimulates gonadotropin secretion in the immature female Sprague-Dawley rat through a pentobarbital- and estradiol-sensitive mechanism but does not alter gonadotropin-releasing hormone (GnRH) secretion by immortalized GnRH neurons in vitro.	2003 Jun	12606454
Liver-selective glucocorticoid antagonists: a novel treatment for type 2 diabetes.	2004 Aug 12	15293993
Selective glucocorticoid receptor nonsteroidal ligands completely antagonize the dexamethasone mediated induction of enzymes involved in gluconeogenesis and glutamine metabolism.	2004 Dec	15698539
Tibolone and its metabolites induce antimitogenesis in human coronary artery smooth muscle cells: role of estrogen, progesterone, and androgen receptors.	2004 Feb	14764805
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	15001543
Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor.	2004 Nov	15308689
Induction of thymocyte apoptosis by systemic administration of concanavalin A in mice: role of TNF-alpha, IFN-gamma and glucocorticoids.	2005 Aug	16047339
Dissociated glucocorticoids equipotently inhibit cytokine- and cAMP-induced matrix degrading proteases in rat mesangial cells.	2005 Aug 1	15963473
p53-dependent inhibition of progestin-induced VEGF expression in human breast cancer cells.	2005 Feb	15860260
The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice.	2005 Feb	15456840
Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol--United States and Canada, 2001-2005.	2005 Jul 29	16049422
The estrogenic activity of synthetic progestins used in oral contraceptives enhances fatty acid synthase-dependent breast cancer cell proliferation and survival.	2005 Jun	15870863
Mechanism of the anti-inflammatory effect of thiazolidinediones: relationship with the glucocorticoid pathway.	2005 May	15684043

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

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 `Sat Dec 16 17:20:50 GMT 2023` Edited by `admin` on `Sat Dec 16 17:20:50 GMT 2023`
Record UNII	320T6RNW1F
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

MIFEPRISTONE

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

(11β,17β)-11-[4-(Dimethylamino)phenyl]-17-hydroxy-17-(1-propyn-1-yl)estra-4,9-dien-3-one

Systematic Name

English

17β-Hydroxy-11β-[4-(dimethylamino)-phenyl]-17α-(prop-1-ynyl)-estra-4,9-dien-3-one

Systematic Name

English

RU486

Code

English

MIFEPRISTONE [MART.]

Common Name

English

NSC-759862

Code

English

RU 38486

Code

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

Estra-4,9-dien-3-one, 11-[4-(dimethylamino)phenyl]-17-hydroxy-17-(1-propyn-1-yl)-, (11β,17β)-

Systematic Name

English

KORLYM

Brand Name

English

Mifepristone [WHO-DD]

Common Name

English

MIFEPRISTONE [ORANGE BOOK]

Common Name

English

RU-38486

Code

English

Classification Tree Code System Code

NDF-RT

N0000000115