Identification

Name
Mifepristone
Accession Number
DB00834  (APRD00432)
Type
Small Molecule
Groups
Approved, Investigational
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]. The two marketed forms of mifepristone are Mifeprex® (mifepristone 200mg) and Korlym™ (mifepristone 300mg). Currently under investigation for use in psychotic depression (phase 3 trials).

Structure
Thumb
Synonyms
  • 11-(4-DIMETHYLAMINO-phenyl)-17-hydroxy-13-methyl-17-prop-1-ynyl-1,2,6,7,8,11,12,13,14,15,16,17-dodec ahydro-cyclopenta[a]phenanthren-3-one
  • Corlux
  • Mifegyne
  • Mifepriston
  • Mifepristona
  • Mifépristone
  • Mifepristonum
External IDs
RU 38486 / RU 486 / RU-38486 / RU-486 / RU486
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
KorlymTablet300 mg/1OralCorcept Therapeutics2012-02-17Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
MifegymisoMifepristone (200 mg) + Misoprostol (200 mcg)Kit; TabletBuccal; OralLinepharma International Limited2017-01-10Not applicableCanada
International/Other Brands
Corlux (Corcept Therapeutics Incorporated) / Mefipil (Abbott) / Mifegyne (Exelgyn Laboratories) / Mifeprex (Danco Laboratories)
Categories
UNII
320T6RNW1F
CAS number
84371-65-3
Weight
Average: 429.5937
Monoisotopic: 429.266779369
Chemical Formula
C29H35NO2
InChI Key
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
IUPAC Name
(10S,11S,14S,15S,17R)-17-[4-(dimethylamino)phenyl]-14-hydroxy-15-methyl-14-(prop-1-yn-1-yl)tetracyclo[8.7.0.0²,⁷.0¹¹,¹⁵]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]

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 and are not candidates for surgery or have had unsuccessful surgery.

Associated Conditions
Associated Therapies
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.

TargetActionsOrganism
AProgesterone receptor
antagonist
Human
AGlucocorticoid receptor
antagonist
Human
UProstate-specific antigenNot AvailableHuman
UNuclear receptor subfamily 1 group I member 2Not AvailableHuman
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 menstrual period, abdominal pain, uterine cramping, nausea, vomiting, and diarrhea.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Mifepristone.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Mifepristone.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Mifepristone is combined with 2,4-thiazolidinedione.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Mifepristone.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be increased when combined with Mifepristone.
4-MethoxyamphetamineThe metabolism of 4-Methoxyamphetamine can be decreased when combined with Mifepristone.
5-(2-methylpiperazine-1-sulfonyl)isoquinolineThe therapeutic efficacy of Mifepristone can be increased when used in combination with 5-(2-methylpiperazine-1-sulfonyl)isoquinoline.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Mifepristone.
6-Deoxyerythronolide BThe metabolism of Mifepristone can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Mifepristone.
Food Interactions
Not Available

References

Synthesis Reference

Narendra Joshi, Anil Khile, Nitin Pradhan, "Novel polymorph form M of mifepristone and process for its preparation." U.S. Patent US20070105828, issued May 10, 2007.

US20070105828
General References
  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:16781264]
  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:14698071]
  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:15790602]
  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:9562577]
  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:14698075]
External Links
Human Metabolome Database
HMDB0014972
KEGG Drug
D00585
KEGG Compound
C07652
PubChem Compound
55245
PubChem Substance
46505795
ChemSpider
49889
BindingDB
18627
ChEBI
50692
ChEMBL
CHEMBL1276308
Therapeutic Targets Database
DAP000090
PharmGKB
PA450500
IUPHAR
2805
Guide to Pharmacology
GtP Drug Page
HET
486
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Mifepristone
ATC Codes
G03XB01 — MifepristoneG03XB51 — Mifepristone, combinations
PDB Entries
1nhz / 2w8y / 3h52 / 3qt0 / 4ltw / 5uc1 / 5uc3
FDA label
Download (46.5 KB)
MSDS
Download (57.1 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingHealth Services ResearchNicotine Dependence1
0TerminatedTreatmentBreast Cancer Invasive Nos / Ductal Carcinoma In Situ1
1Active Not RecruitingTreatmentAnxiety Disorders1
1CompletedBasic ScienceHealthy Volunteers2
1CompletedOtherDrug Interaction Potentiation / Healthy Volunteers1
1CompletedOtherHealthy Volunteers1
1CompletedTreatmentCancer, Breast / Lung Cancer Non-Small Cell Cancer (NSCLC) / Prostate Cancer / Prostatic Neoplasms / Recurrent Ovarian Epithelial Cancer / Sarcomas / Transitional Cell Carcinoma1
1CompletedTreatmentDepression1
1CompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Recurrent Fallopian Tube Cancer / Recurrent Ovarian Epithelial Cancer / Recurrent Primary Peritoneal Cavity Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
1CompletedTreatmentMale Breast Cancer / Recurrent Breast Cancer / Stage IIIA Breast Cancer / Stage IIIB Breast Cancer / Stage IIIC Breast Cancer / Stage IV Breast Cancer1
1CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
1CompletedTreatmentUterine Leiomyomas1
1WithdrawnTreatmentSecond Trimester Labor Induction1
1, 2CompletedTreatmentAnxiety Disorders1
1, 2CompletedTreatmentDiabetes Mellitus (DM) / Endocrine Diseases1
1, 2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
1, 2CompletedTreatmentSubclinical Cushing's1
1, 2RecruitingTreatmentHormone-Resistant Prostate Cancer / Recurrent Prostate Cancer / Stage IV Prostate Cancer1
2CompletedNot AvailableAlcohol Dependence1
2CompletedNot AvailableWeight-Gain Prevention1
2CompletedPreventionHealthy Volunteers1
2CompletedTreatmentACTH / Cortisol Resistance / Glucocorticoid therapy / Mineralcorticoid / Negative Feedback1
2CompletedTreatmentAdenocarcinoma, Prostate / Prostate Cancer1
2CompletedTreatmentBipolar Disorder (BD)1
2CompletedTreatmentCancer of the Ovary / Fallopian Tube Cancer / Primary Peritoneal Cavity Cancer1
2CompletedTreatmentCentral Serous Chorioretinopathy (CSC)1
2CompletedTreatmentEndometrial Cancers1
2CompletedTreatmentHepatitis C Virus Infection1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections1
2CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
2CompletedTreatmentPregnancy Termination1
2CompletedTreatmentUterine Leiomyomas / Vaginal haemorrhage1
2CompletedTreatmentWomen in Need of Long Acting Reversibel Cntraception With the Intrauterine Levonorgestrel Releasing System, Mirena1
2Not Yet RecruitingTreatmentAbortion in Second Trimester1
2RecruitingNot AvailablePosttraumatic Stress Disorders1
2RecruitingDiagnosticCushing's Syndrome1
2RecruitingPreventionWomen With Mutations in the Breast Cancer Susceptibility Genes BRCA-1 and -2 / Women With Mutations in the Breast Cancer Susceptibility Genes BRCA1,21
2RecruitingTreatmentAdvanced HER2-negative Breast Cancer1
2RecruitingTreatmentAlcohol Abuse / Alcohol Dependence / Alcohol Use Disorders (AUD)1
2RecruitingTreatmentBorderline Personality Disorder (BPD)1
2RecruitingTreatmentCancer, Breast1
2RecruitingTreatmentInsulin Resistance / Type 2 Diabetes Mellitus1
2RecruitingTreatmentLung Cancer Non-Small Cell Cancer (NSCLC)1
2RecruitingTreatmentPost Traumatic Stress Disorder (PTSD)1
2TerminatedTreatmentAlzheimer's Disease (AD)1
2TerminatedTreatmentCushing's Syndrome1
2TerminatedTreatmentLeiomyomas1
2Unknown StatusNot AvailablePregnancy Termination1
2WithdrawnTreatmentDepression, Bipolar1
2, 3CompletedTreatmentDependence, Cocaine1
2, 3CompletedTreatmentEndometriosis1
2, 3CompletedTreatmentUterine Leiomyomas2
2, 3RecruitingTreatmentEndometriosis of Uterus1
2, 3TerminatedTreatmentDepressive Disorders / Major Depressive Disorder (MDD) / Psychotic Disorder NOS1
3Active Not RecruitingTreatmentSpontaneous Abortions1
3Active Not RecruitingTreatmentFetal mortality1
3CompletedTreatmentCervical Preparation1
3CompletedTreatmentCushing's Disease / Cushing's Syndrome1
3CompletedTreatmentCushing's Syndrome2
3CompletedTreatmentLeiomyomas1
3CompletedTreatmentMajor Depressive Disorder (MDD)2
3CompletedTreatmentMajor Depressive Disorder (MDD) / Psychotic Disorder NOS3
3CompletedTreatmentMedical Abortion1
3CompletedTreatmentMeningiomas1
3RecruitingTreatmentMedical; Abortion, Fetus1
3RecruitingTreatmentMissed Miscarriage1
3TerminatedTreatmentAffective Disorders, Psychotic / Depressive Disorders1
3TerminatedTreatmentMajor Depression With Psychotic Features / Psychosis / Psychotic Depression / Severe Major Depression With Psychotic Features1
3TerminatedTreatmentPregnancy Termination1
3Unknown StatusTreatmentDepression / Major Depressive Disorder (MDD)1
3Unknown StatusTreatmentMedical Abortion1
3Unknown StatusTreatmentSurgical Abortion1
3WithdrawnTreatmentCushing's Disease1
4Active Not RecruitingTreatmentAbortion Failure1
4Active Not RecruitingTreatmentMissed Abortion / Pregnancy1
4CompletedNot AvailableAnxiety Disorders / Posttraumatic Stress Disorders / Reconsolidation1
4CompletedHealth Services ResearchAbortion, Therapeutic1
4CompletedHealth Services ResearchMenstrual Regulation1
4CompletedPreventionEarly Pregnancy Termination / Medical Abortion / Postabortion Contraception1
4CompletedTreatmentAbortion Seekers1
4CompletedTreatmentAbortion, 3 Months1
4CompletedTreatmentAnembryonic Pregnancy / Gestation Abnormality / Intrauterine Fetal Demise Term1
4CompletedTreatmentChronic Multisymptom Illness in Gulf War Veterans1
4CompletedTreatmentComplete Uterine Evacuation After Use of Study Drugs1
4CompletedTreatmentComplications, Pregnancy1
4CompletedTreatmentMedical Abortion2
4CompletedTreatmentMild Hypercortisolism1
4CompletedTreatmentMissed Abortion2
4CompletedTreatmentPost Traumatic Stress Disorder (PTSD)1
4CompletedTreatmentPregnancy Termination1
4Not Yet RecruitingTreatmentAbortion in Second Trimester1
4Not Yet RecruitingTreatmentMedical Abortion1
4RecruitingHealth Services ResearchAbortion Early / Pregnancy Related1
4RecruitingTreatmentEarly Pregnancy Failure1
4RecruitingTreatmentFetal mortality / Intrauterine Fetal Demise1
4RecruitingTreatmentLegally Induced Abortion Without Mention of Complication1
4RecruitingTreatmentSecond Trimester Abortions1
4RecruitingTreatmentUterine Leiomyomas1
Not AvailableCompletedNot AvailableComplete Abortion1
Not AvailableCompletedNot AvailablePost Traumatic Stress Disorder (PTSD)1
Not AvailableCompletedHealth Services ResearchPregnancy Termination1
Not AvailableCompletedHealth Services ResearchTermination of Pregnancy2
Not AvailableCompletedTreatmentDepression1
Not AvailableCompletedTreatmentLegally Induced Abortion Without Mention of Complication1
Not AvailableCompletedTreatmentPregnancy Termination7
Not AvailableCompletedTreatmentPregnancy termination therapy1
Not AvailableCompletedTreatmentTermination of Pregnancy Second Trimester1
Not AvailableRecruitingBasic ScienceAlcohol Use Disorder (AUD)1
Not AvailableRecruitingTreatmentCancer, Breast1
Not AvailableSuspendedTreatmentLegally Induced Abortion Without Mention of Complication1
Not AvailableTerminatedBasic ScienceCervical Prostaglandin EP3 Receptors / Pregnancy1
Not AvailableTerminatedPreventionMalignancies1
Not AvailableTerminatedTreatmentAbortions spontaneous / Anembryonic Pregnancy / Early Pregnancy Failure / Fetal mortality1
Not AvailableUnknown StatusTreatmentAbortion Techniques / Mifepristone / Misoprostol / Pregnancy Termination1
Not AvailableUnknown StatusTreatmentComplete Abortion1

Pharmacoeconomics

Manufacturers
  • Danco laboratories llc
Packagers
  • Danco Labs LLC
Dosage forms
FormRouteStrength
TabletOral300 mg/1
Kit; tabletBuccal; Oral
Prices
Unit descriptionCostUnit
Mifeprex 200 mg tablet90.0USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8921348No2014-12-302028-08-27Us
US9829495No2017-11-282036-08-15Us
US9943526No2018-04-172036-04-20Us
US10006924No2016-08-122036-08-12Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)191-196 °CFDA Label
water solubilityPoorly solubleFDA Label
logP4.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00336 mg/mLALOGPS
logP5.33ALOGPS
logP5.13ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)12.87ChemAxon
pKa (Strongest Basic)4.89ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area40.54 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity132.58 m3·mol-1ChemAxon
Polarizability50.71 Å3ChemAxon
Number of Rings5ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.7135
Caco-2 permeable+0.6716
P-glycoprotein substrateSubstrate0.643
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IIInhibitor0.8387
Renal organic cation transporterNon-inhibitor0.8177
CYP450 2C9 substrateNon-substrate0.7606
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.8334
CYP450 1A2 substrateInhibitor0.9106
CYP450 2C9 inhibitorNon-inhibitor0.6293
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorInhibitor0.796
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6129
Ames testNon AMES toxic0.856
CarcinogenicityNon-carcinogens0.825
BiodegradationNot ready biodegradable0.9971
Rat acute toxicity2.7705 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9177
hERG inhibition (predictor II)Non-inhibitor0.6879
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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
MS/MS Spectrum - , positiveLC-MS/MSsplash10-001i-0332900000-9cbfa7fe6866f246577a
1H NMR Spectrum1D NMRNot Applicable
13C NMR Spectrum1D NMRNot Applicable

Taxonomy

Description
This compound belongs to the class of organic compounds known as oxosteroids. These are steroid derivatives carrying a C=O group attached to steroid skeleton.
Kingdom
Organic compounds
Super Class
Lipids and lipid-like molecules
Class
Steroids and steroid derivatives
Sub Class
Oxosteroids
Direct Parent
Oxosteroids
Alternative Parents
3-oxosteroids / 17-hydroxysteroids / Dialkylarylamines / Aniline and substituted anilines / Cyclohexenones / Ynones / Tertiary alcohols / Cyclic alcohols and derivatives / Organopnictogen compounds / Organic oxides
show 1 more
Substituents
3-oxosteroid / Hydroxysteroid / Oxosteroid / 17-hydroxysteroid / Tertiary aliphatic/aromatic amine / Dialkylarylamine / Aniline or substituted anilines / Cyclohexenone / Benzenoid / Monocyclic benzene moiety
show 17 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
3-oxo steroid (CHEBI:50692) / Estrane and derivatives (C07652)

Targets

Details
1. Progesterone receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
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. 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:10374120]
  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:10682471]
  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:10699595]
  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:10806733]
  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:11783365]
  6. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
Details
2. Glucocorticoid receptor
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Zinc ion binding
Specific Function
Receptor for glucocorticoids (GC). Has a dual mode of action: as a transcription factor that binds to glucocorticoid response elements (GRE), both for nuclear and mitochondrial DNA, and as a modula...
Gene Name
NR3C1
Uniprot ID
P04150
Uniprot Name
Glucocorticoid receptor
Molecular Weight
85658.57 Da
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:10796070]
  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:15120421]
  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:15336699]
  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:15909120]
  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:16723527]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.
Specific Function
Endopeptidase activity
Gene Name
KLK3
Uniprot ID
P07288
Uniprot Name
Prostate-specific antigen
Molecular Weight
28741.1 Da
References
  1. Kang Z, Janne OA, Palvimo JJ: Coregulator recruitment and histone modifications in transcriptional regulation by the androgen receptor. Mol Endocrinol. 2004 Nov;18(11):2633-48. Epub 2004 Aug 12. [PubMed:15308689]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Kretschmer XC, Baldwin WS: CAR and PXR: xenosensors of endocrine disrupters? Chem Biol Interact. 2005 Aug 15;155(3):111-28. [PubMed:16054614]

Enzymes

Details
1. Cytochrome P450 3A4
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Inducer
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
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Yueh MF, Kawahara M, Raucy J: High volume bioassays to assess CYP3A4-mediated drug interactions: induction and inhibition in a single cell line. Drug Metab Dispos. 2005 Jan;33(1):38-48. Epub 2004 Oct 1. [PubMed:15466163]
  3. Jang GR, Benet LZ: Antiprogestin pharmacodynamics, pharmacokinetics, and metabolism: implications for their long-term use. J Pharmacokinet Biopharm. 1997 Dec;25(6):647-72. [PubMed:9697076]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Soars MG, Grime K, Riley RJ: Comparative analysis of substrate and inhibitor interactions with CYP3A4 and CYP3A5. Xenobiotica. 2006 Apr;36(4):287-99. doi: 10.1080/00498250500446208 . [PubMed:16684709]
  3. Khan KK, He YQ, Correia MA, Halpert JR: Differential oxidation of mifepristone by cytochromes P450 3A4 and 3A5: selective inactivation of P450 3A4. Drug Metab Dispos. 2002 Sep;30(9):985-90. [PubMed:12167563]
  4. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxygen binding
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 oxidizes a variety of structurally un...
Gene Name
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
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...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  2. He K, Woolf TF, Hollenberg PF: Mechanism-based inactivation of cytochrome P-450-3A4 by mifepristone (RU486). J Pharmacol Exp Ther. 1999 Feb;288(2):791-7. [PubMed:9918590]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Mifepristone FDA Label [File]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Inhibitor
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. PDR [Link]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
Inducer
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
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:11297522]
  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:7982498]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Transporter activity
Specific Function
Mediates export of organic anions and drugs from the cytoplasm. Mediates ATP-dependent transport of glutathione and glutathione conjugates, leukotriene C4, estradiol-17-beta-o-glucuronide, methotre...
Gene Name
ABCC1
Uniprot ID
P33527
Uniprot Name
Multidrug resistance-associated protein 1
Molecular Weight
171589.5 Da
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:10329417]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Transporter activity
Specific Function
Involved in the ATP-dependent secretion of bile salts into the canaliculus of hepatocytes.
Gene Name
ABCB11
Uniprot ID
O95342
Uniprot Name
Bile salt export pump
Molecular Weight
146405.83 Da
References
  1. Pedersen JM, Matsson P, Bergstrom CA, Hoogstraate J, Noren A, LeCluyse EL, Artursson P: Early identification of clinically relevant drug interactions with the human bile salt export pump (BSEP/ABCB11). Toxicol Sci. 2013 Dec;136(2):328-43. doi: 10.1093/toxsci/kft197. Epub 2013 Sep 6. [PubMed:24014644]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 04:51