mifepristone ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
steroidal compounds acting on progesterone receptors 1805 84371-65-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • mifepristone
  • mifegyne
  • mifeprex
  • mifestone
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.
  • Molecular weight: 429.60
  • Formula: C29H35NO2
  • CLOGP: 4.47
  • LIPINSKI: 0
  • HAC: 3
  • HDO: 1
  • TPSA: 40.54
  • ALOGS: -5.11
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.20 g O
0.20 g O

ADMET properties:

PropertyValueReference
MRTD (Maximum Recommended Therapeutic Daily Dose) 23.28 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Hosey CM, Chan R, Benet LZ
BA (Bioavailability) 69 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.45 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.50 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 16.60 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 0.00 mg/mL Bocci G, Oprea TI, Benet LZ

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 4.146 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 0.966 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 57.677 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 38.194 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.340 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.150 % High 1
herg hERG pIC50 4.592 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 36.308 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 201.837 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.390 % High 1
kinase-safety-class ACVR2B,AKT2,AKT3,AURKA,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,DDR1,DYRK1B,EIF2AK3,EPHB4,ERBB2,GRK2,GSK3B,ITK,JAK2,JAK3,MAP2K6,MAP3K7,MAPK10,MAPK7,MAPK9,MAPKAPK2,MET,NTRK2,PDK1,PDK2,PDK4,PDPK1,PIK3CA,PIK3CB,PIM2,PRKDC,STK33,SYK,TEK,TGFBR1,TTK,ZAP70 43
kinase-selectivity-class GRK2,MAP2K6,MAP3K14 3
mdck-mdr1-bcrp-efflux MDCK-MDR1-BCRP efflux ratio 0.641 Moderate 0.74
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 1.355 High 1
mh-clint Mouse hepatocyte intrinsic clearance 159.956 High 1
mppb Mouse plasma protein binding (% unbound) 0.530 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 16.255 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 1.150 % High 1
rat-kpuu-brain Rat brain Kpuu 0.545 % Moderate 0.74
rh-clint Rat hepatocyte intrinsic clearance 202.768 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 8.750 % High 1
rppb Rat plasma protein binding (% unbound) 0.610 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 17.179 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 28, 2000 FDA DANCO LABS LLC
April 28, 2023 PMDA Linepharma K.K.

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Abortion incomplete 4820.87 48.57 670 5006 2470 90620301
Haemorrhage 2499.81 48.57 621 5055 68748 90554023
Pregnancy 696.47 48.57 225 5451 61822 90560949
Endometritis 457.36 48.57 77 5599 1123 90621648
Anaemia 283.55 48.57 208 5468 352594 90270177
Induced abortion failed 202.79 48.57 30 5646 175 90622596
Retained products of conception 180.49 48.57 26 5650 122 90622649
Drug ineffective for unapproved indication 172.90 48.57 84 5592 66560 90556211
Vaginal haemorrhage 127.31 48.57 54 5622 31217 90591554
Muscle spasms 126.11 48.57 113 5563 251770 90371001
Abortion induced incomplete 125.04 48.57 16 5660 22 90622749
Intermenstrual bleeding 117.61 48.57 37 5639 9186 90613585
Congenital multiplex arthrogryposis 81.39 48.57 12 5664 68 90622703
Uterine haemorrhage 77.33 48.57 23 5653 4729 90618042
Ruptured ectopic pregnancy 76.39 48.57 15 5661 528 90622243
Pelvic inflammatory disease 73.16 48.57 18 5658 1812 90620959
Ectopic pregnancy 72.05 48.57 20 5656 3221 90619550
Uterine rupture 70.29 48.57 16 5660 1153 90621618
Truncus arteriosus persistent 68.28 48.57 13 5663 388 90622383
Congenital cardiovascular anomaly 65.47 48.57 13 5663 485 90622286
Blood potassium decreased 64.28 48.57 39 5637 47688 90575083
Cardiac septal defect 59.57 48.57 13 5663 772 90621999
Syncope 59.36 48.57 56 5620 132607 90490164
Pelvic pain 57.46 48.57 25 5651 15332 90607439
Ventricular septal defect 53.88 48.57 18 5658 5389 90617382
Heart disease congenital 49.98 48.57 13 5663 1636 90621135
Dizziness 49.74 48.57 112 5564 589172 90033599

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Maternal exposure during pregnancy 66.52 52.12 15 394 6963 42613963
Foetal exposure during pregnancy 56.64 52.12 20 389 47291 42573635

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Abortion incomplete 4977.61 43.42 666 4679 2406 110581548
Haemorrhage 2362.01 43.42 614 4731 106078 110477876
Pregnancy 797.51 43.42 225 5120 50842 110533112
Endometritis 441.82 43.42 70 5275 904 110583050
Anaemia 246.41 43.42 206 5139 546880 110037074
Induced abortion failed 201.01 43.42 28 5317 135 110583819
Retained products of conception 196.76 43.42 27 5318 114 110583840
Muscle spasms 135.54 43.42 110 5235 278047 110305907
Vaginal haemorrhage 119.04 43.42 45 5300 25029 110558925
Abortion induced incomplete 104.49 43.42 13 5332 19 110583935
Intermenstrual bleeding 100.77 43.42 29 5316 6905 110577049
Drug ineffective for unapproved indication 94.71 43.42 60 5285 102778 110481176
Uterine haemorrhage 90.24 43.42 23 5322 3471 110580483
Ectopic pregnancy 84.02 43.42 20 5325 2277 110581677
Ruptured ectopic pregnancy 81.96 43.42 15 5330 470 110583484
Pelvic inflammatory disease 80.43 43.42 18 5327 1562 110582392
Pain 75.18 43.42 151 5194 954804 109629150
Uterine rupture 74.64 43.42 15 5330 776 110583178
Blood potassium decreased 61.12 43.42 36 5309 54078 110529876
Pelvic pain 59.35 43.42 24 5321 15918 110568036
Heavy menstrual bleeding 58.74 43.42 24 5321 16341 110567613
Dizziness 53.09 43.42 109 5236 698084 109885870
Syncope 51.66 43.42 56 5289 202480 110381474
Post abortion infection 47.04 43.42 6 5339 12 110583942
Vaginal odour 44.93 43.42 9 5336 458 110583496
Maternal exposure during pregnancy 44.38 43.42 58 5287 254825 110329129

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC G03XB01 GENITO URINARY SYSTEM AND SEX HORMONES
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
Progesterone receptor modulators
ATC G03XB51 GENITO URINARY SYSTEM AND SEX HORMONES
SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
OTHER SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
Progesterone receptor modulators
FDA MoA N0000000115 Progestational Hormone Receptor Antagonists
MeSH PA D000021 Abortifacient Agents, Steroidal
MeSH PA D000080066 Contraceptive Agents, Hormonal
MeSH PA D003271 Contraceptive Agents, Female
MeSH PA D003280 Contraceptives, Oral, Synthetic
MeSH PA D003283 Contraceptives, Postcoital, Synthetic
MeSH PA D006727 Hormone Antagonists
MeSH PA D008186 Luteolytic Agents
MeSH PA D008600 Menstruation-Inducing Agents
MeSH PA D012102 Reproductive Control Agents
FDA EPC N0000175841 Progestin Antagonist
CHEBI has role CHEBI:22587 antiviral agent
CHEBI has role CHEBI:35469 antidepressant
CHEBI has role CHEBI:35474 anxiolytic drug
CHEBI has role CHEBI:35476 antipsychotic agent
CHEBI has role CHEBI:35526 hypoglycemic agent
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:49020 hormone antagonist
CHEBI has role CHEBI:49323 contraceptive drug
CHEBI has role CHEBI:49326 synthetic oral contraceptive
CHEBI has role CHEBI:50691 abortifacient
CHEBI has role CHEBI:64946 anti-HIV agent

Related Drugs by ATC class:

G03XB Progesterone receptor modulators 1 drug

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Pregnancy with abortive outcome indication 363681007
Severe adrenal insufficiency contraindication 24867002
Ectopic pregnancy contraindication 34801009 DOID:0060329
Erythropoietic protoporphyria contraindication 51022005 DOID:13270
Hepatic porphyria contraindication 55056006 DOID:3133
Variegate porphyria contraindication 58275005 DOID:4346
Porphyria cutanea tarda contraindication 61860000 DOID:3132
Blood coagulation disorder contraindication 64779008 DOID:1247
Intermenstrual bleeding - irregular contraindication 64996003
Miscarriage with sepsis contraindication 67465009
Bacterial infectious disease contraindication 87628006
Leukocytosis contraindication 111583006
Incomplete miscarriage contraindication 156072005
Acute intermittent porphyria contraindication 234422006 DOID:3890
Adrenal cortical hypofunction contraindication 386584007 DOID:10493
Postabortal Hemorrhage contraindication
Uterine Adnexal Mass contraindication




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.08 acidic
pKa2 3.7 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 8921348 Aug. 27, 2028 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10842801 Nov. 15, 2032 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10500216 March 5, 2033 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10166242 April 20, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10166243 April 20, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10660904 April 20, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 9943526 April 20, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10006924 Aug. 12, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10495650 Aug. 12, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 9829495 Aug. 15, 2036 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10151763 Jan. 18, 2037 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10195214 June 19, 2037 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10842800 June 19, 2037 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 11969435 June 19, 2037 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 12097210 June 19, 2037 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10231983 Aug. 22, 2038 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10314850 Aug. 22, 2038 TREATING CUSHINGS SYNDROME
300MG KORLYM CORCEPT THERAP N202107 Feb. 17, 2012 RX TABLET ORAL 10780097 Aug. 22, 2038 TREATING CUSHINGS SYNDROME

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Glucocorticoid receptor Nuclear hormone receptor ANTAGONIST IC50 9 WOMBAT-PK CHEMBL
Progesterone receptor Nuclear hormone receptor ANTAGONIST Ki 8.74 WOMBAT-PK CHEMBL
Cytochrome P450 3A4 Enzyme Ki 6.64 WOMBAT-PK
Alpha-2B adrenergic receptor GPCR Ki 4.92 DRUG MATRIX
Nuclear receptor subfamily 1 group I member 2 Nuclear hormone receptor AGONIST EC50 5 IUPHAR
Kappa-type opioid receptor GPCR Ki 5.10 DRUG MATRIX
Mineralocorticoid receptor Nuclear hormone receptor IC50 5.68 WOMBAT-PK
Estrogen receptor Nuclear hormone receptor IC50 5.30 CHEMBL
Androgen receptor Nuclear hormone receptor Ki 8.33 WOMBAT-PK
Estrogen receptor beta Nuclear hormone receptor Ki 5.54 CHEMBL
Tyrosine-protein kinase Fyn Kinase IC50 4.67 DRUG MATRIX
Mitogen-activated protein kinase 14 Kinase IC50 4.08 DRUG MATRIX
Mu-type opioid receptor GPCR Ki 6.00 DRUG MATRIX
Sigma non-opioid intracellular receptor 1 Membrane receptor Ki 4.96 DRUG MATRIX
Androgen receptor Transcription factor Ki 8.26 DRUG MATRIX
Arachidonate 15-lipoxygenase Enzyme IC50 6.26 DRUG MATRIX
Progesterone receptor Transcription factor Ki 9.37 DRUG MATRIX
Glucocorticoid receptor Transcription factor IC50 8.85 CHEMBL
Progesterone receptor Transcription factor IC50 8.46 CHEMBL
P-glycoprotein 3 Transporter Kd 4.70 CHEMBL
Glucocorticoid receptor Nuclear hormone receptor IC50 7.70 CHEMBL
Glucocorticoid receptor Nuclear hormone receptor IC50 7.96 CHEMBL
Glucocorticoid receptor Nuclear hormone receptor IC50 7.70 CHEMBL

External reference:

IDSource
4021235 VUID
N0000148679 NUI
D00585 KEGG_DRUG
4021235 VANDF
C0026088 UMLSCUI
CHEBI:50692 CHEBI
486 PDB_CHEM_ID
CHEMBL1276308 ChEMBL_ID
D015735 MESH_DESCRIPTOR_UI
DB00834 DRUGBANK_ID
55245 PUBCHEM_CID
2805 IUPHAR_LIGAND_ID
5752 INN_ID
320T6RNW1F UNII
284781 RXNORM
15775 MMSL
231857 MMSL
40538 MMSL
d04718 MMSL
004008 NDDF
129483007 SNOMEDCT_US
395796009 SNOMEDCT_US
320T6RNW1F INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Mifepristone HUMAN PRESCRIPTION DRUG LABEL 1 0591-4390 TABLET, FILM COATED 300 mg ORAL ANDA 28 sections
Mifepristone HUMAN PRESCRIPTION DRUG LABEL 1 43393-001 TABLET 200 mg ORAL ANDA 20 sections
MIFEPREX HUMAN PRESCRIPTION DRUG LABEL 1 64875-001 TABLET 200 mg ORAL NDA 28 sections
Korlym HUMAN PRESCRIPTION DRUG LABEL 1 76346-073 TABLET 300 mg ORAL NDA 28 sections
Mifepristone HUMAN PRESCRIPTION DRUG LABEL 1 76346-654 TABLET 300 mg ORAL NDA 28 sections
Mifepristone HUMAN PRESCRIPTION DRUG LABEL 1 84670-014 TABLET 200 mg ORAL ANDA 20 sections