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Compound Detail

CHEMBL1276308

MIFEPRISTONE
💊 Approved Drug
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💊 Approved Drug
CC#C[C@]1(O)CC[C@H]2[C@@H]3CCC4=CC(=O)CCC4=C3[C@@H](c3ccc(N(C)C)cc3)C[C@@]21C

Basic Information

ChEMBL ID CHEMBL1276308
Name MIFEPRISTONE
Phase Approved
Structure Type MOL
InChI Key VKHAHZOOUSRJNA-GCNJZUOMSA-N
Therapeutic ✓ Yes

Known Names

Korlym Mifegyne Mifeprex Mifepristona Mifepristone NSC-759862 RU 38486 RU 486 RU-38486 RU-486 RU486
32
Targets
231
Activities
4
Assay Types
30
PK Parameters
20
Publications
11
Known Names
20
Indications
2
Mechanisms

Molecular Properties

429.6
MW (Da)
5.41
ALogP
3
HBA
1
HBD
40.5
PSA (Ų)
0.64
QED
1
Ro5 Violations
2
Rot. Bonds

Drug Information

Molecule Type Small molecule
First Approval 2000
Availability Prescription
Chirality Single Enantiomer

Routes of Administration

Oral

Flags

Black Box Warning Natural Product
USAN Stem -pris-; -pristone
USAN Year 1998

Extended Properties

Molecular Formula C29H35NO2
MW 429.60
Aromatic Rings 1
Heavy Atoms 32
NP-Likeness 1.23

Mechanism of Action

Mechanism Action Type Target Direct Efficacy
Glucocorticoid receptor antagonist ANTAGONIST Glucocorticoid receptor
Progesterone receptor antagonist ANTAGONIST Progesterone receptor

Indications

Cushing Syndrome Abortion, Spontaneous Abortion, Spontaneous Breast Neoplasms Breast Neoplasms Depressive Disorder Depressive Disorder, Major Leiomyoma Leiomyoma Meningioma Mental Disorders Pituitary ACTH Hypersecretion Adenomyosis Alcoholism Alcoholism Alzheimer Disease Bipolar Disorder Borderline Personality Disorder Carcinoma, Non-Small-Cell Lung Central Serous Chorioretinopathy

ATC Classification

G03XB01
mifepristone
Level 1: GENITO URINARY SYSTEM AND SEX HORMONES
Level 2: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM
G03XB51
mifepristone, combinations
Level 1: GENITO URINARY SYSTEM AND SEX HORMONES
Level 2: SEX HORMONES AND MODULATORS OF THE GENITAL SYSTEM

Drug Warnings

Black Box Warning
General Warning
Country: United States
Black Box Warning
gastrointestinal toxicity
Country: United States
Black Box Warning
infectious disease
Country: United States
Black Box Warning
cardiotoxicity
Country: United States
Black Box Warning
hematological toxicity
Country: United States

Activity Summary

IC50 164 meas. best 10.68
Ki 55 meas. best 10.05
EC50 10 meas. best 9.52
Kd 2 meas. best 7.82

Target Activity Profile

Target Type Best pChEMBL Mean pChEMBL Best (nM) # Data
Progesterone receptor
CHEMBL208
IC50 10.68 9.425 0.0 42
Glucocorticoid receptor
CHEMBL2034
Ki 10.05 8.9443 0.1 21
Progesterone receptor
CHEMBL208
Ki 9.6 8.7285 0.3 13
Glucocorticoid receptor
CHEMBL2034
IC50 9.53 8.5435 0.3 49
Progesterone receptor
CHEMBL208
EC50 9.52 9.52 0.3 1
Progesterone receptor
CHEMBL1909044
Ki 9.37 9.37 0.4 1
Glucocorticoid receptor
CHEMBL2034
EC50 9.22 7.9933 0.6 3
Androgen receptor
CHEMBL1871
Ki 9.19 8.2433 0.7 6
Unchecked
CHEMBL612545
IC50 9.15 6.54 0.7 6
Tegument protein VP16
CHEMBL4218
EC50 9.15 9.15 0.7 1
Androgen receptor
CHEMBL1871
IC50 9.0 8.0783 1.0 18
Glucocorticoid receptor
CHEMBL3368
IC50 8.85 7.418 1.4 5
Glucocorticoid receptor
CHEMBL3144
IC50 8.66 8.66 2.2 1
Glucocorticoid receptor
CHEMBL3368
EC50 8.6 8.6 2.5 1
Progesterone receptor
CHEMBL1909044
IC50 8.49 8.49 3.2 1
Progesterone receptor
CHEMBL2596
IC50 8.46 8.46 3.5 1
Androgen receptor
CHEMBL3072
Ki 8.26 8.26 5.6 1
Androgen receptor
CHEMBL3072
IC50 8.08 8.08 8.3 1
Androgen receptor
CHEMBL1871
EC50 8.0 7.9467 10.0 3
Glucocorticoid receptor
CHEMBL4295956
IC50 7.96 7.835 10.9 2
Glucocorticoid receptor
CHEMBL2034
Kd 7.82 7.82 15.0 1
Progesterone receptor
CHEMBL2596
EC50 7.8 7.8 15.8 1
Glucocorticoid receptor
CHEMBL4105966
IC50 7.7 7.595 20.2 2
Polyunsaturated fatty acid lipoxygenase ALOX15
CHEMBL4358
IC50 6.26 6.26 555.0 1
Mineralocorticoid receptor
CHEMBL1994
IC50 6.23 5.845 590.0 6
Mineralocorticoid receptor
CHEMBL1994
Ki 6.19 6.13 640.0 2
Estrogen receptor beta
CHEMBL242
IC50 6.09 6.09 812.0 1
NON-PROTEIN TARGET
CHEMBL3879801
IC50 6.05 6.05 900.0 1
Mu-type opioid receptor
CHEMBL233
Ki 6.0 6.0 997.0 1
Cytochrome P450 2C8
CHEMBL3721
IC50 5.82 5.82 1500.0 2
Bile salt export pump
CHEMBL6020
IC50 5.7 5.7 2020.0 1
Estrogen receptor
CHEMBL2093866
IC50 5.65 5.65 2244.0 1
Mu-type opioid receptor
CHEMBL233
IC50 5.61 5.61 2457.0 1
Estrogen receptor beta
CHEMBL242
Ki 5.54 5.54 2876.0 1
Plasmodium falciparum
CHEMBL364
IC50 5.4 5.0571 3981.1 7
Cytochrome P450 3A4
CHEMBL340
Ki 5.33 5.33 4700.0 2
Cytochrome P450 2C9
CHEMBL3397
IC50 5.31 5.31 4900.0 1
Estrogen receptor
CHEMBL206
IC50 5.3 5.1325 5000.0 4
Unchecked
CHEMBL612545
Ki 5.28 4.8933 5310.0 3
Estrogen receptor
CHEMBL206
Ki 5.17 5.17 6754.0 1
Kappa-type opioid receptor
CHEMBL237
Ki 5.09 5.09 8038.0 1
Cytochrome P450 3A4
CHEMBL340
IC50 5.02 5.02 9500.0 2
Sigma non-opioid intracellular receptor 1
CHEMBL287
Ki 4.96 4.96 11047.0 1
Alpha-2B adrenergic receptor
CHEMBL1942
Ki 4.92 4.92 12082.0 1
SUM149PT
CHEMBL4296497
IC50 4.82 4.82 15000.0 1
ATP-dependent translocase ABCB1
CHEMBL2573
Kd 4.7 4.7 20000.0 1
Kappa-type opioid receptor
CHEMBL237
IC50 4.7 4.7 20096.0 1
Tyrosine-protein kinase Fyn
CHEMBL1841
IC50 4.67 4.67 21357.0 1
MCF7
CHEMBL387
IC50 4.62 4.62 24030.0 1
Sigma non-opioid intracellular receptor 1
CHEMBL287
IC50 4.58 4.58 26280.0 1

Pharmacokinetic Data

Parameter Value Units Species
AUC 1.863 - Mus musculus
AUC 1.371 - Mus musculus
AUC 446.0 ng.hr.mL-1 Rattus norvegicus
AUC 3571.0 ng.hr.mL-1 Rattus norvegicus
AUC 77955.22 ng.hr.mL-1 Homo sapiens
AUC - - Rattus norvegicus
AUC 85.0 ng.hr.mL-1 Rattus norvegicus
AUC 2420.0 ng.hr.mL-1 Rattus norvegicus
AUC 1970.0 ng.hr.mL-1 Rattus norvegicus
AUC 85.0 ng.hr.mL-1 Rattus norvegicus
CL 115.0 mL.min-1.kg-1 Mus musculus
CL 50.0 mL.min-1.kg-1 Rattus norvegicus
CL 0.33 mL.min-1.kg-1 Homo sapiens
CL 15.6 mL.min-1.kg-1 Canis lupus familiaris
CL 24.2 mL.min-1.kg-1 Macaca
CL 92.5 mL.min-1.g-1 -
CL 26.92 uL.min-1.(10^6cells)-1 Homo sapiens
CL 79.0 mL.min-1.g-1 Homo sapiens
CL 61.67 mL.min-1.kg-1 Rattus norvegicus
CL 61.67 mL.min-1.kg-1 Rattus norvegicus
Cmax 6510.71 nM Mus musculus
Cmax 69.83 nM Mus musculus
Cmax 125.23 nM Rattus norvegicus
Cmax 5819.37 nM Homo sapiens
Cmax - - Rattus norvegicus
Cmax 55.87 nM Rattus norvegicus
Cmax 837.99 nM Rattus norvegicus
Cmax 55.87 nM Rattus norvegicus
F 31.0 % Mus musculus
F 6.4 % Rattus norvegicus

Activity Data Samples

Top measurements by pChEMBL value

Target Type Rel. Value Units pChEMBL Assay PubMed
Progesterone receptor IC50 = 0.021 nM 10.68 Antagonist activity at progesterone receptor in human T47D-C124 cells transfecte... 19216549
Progesterone receptor IC50 = 0.025 nM 10.6 In vitro antagonist potency in transactivation assay in neuroblastoma cells expr... 11150172
Progesterone receptor IC50 = 0.028 nM 10.55 In vitro antagonist potency in transactivation assay in neuroblastoma cells expr... 11150172
Progesterone receptor IC50 = 0.045 nM 10.35 Antagonist activity at progesterone receptor in human T47D cells assessed as inh... 19216549
Progesterone receptor IC50 = 0.05 nM 10.3 Antiprogestagenic activity at progesterone receptor in human T47D cells assessed... 20149664
Progesterone receptor IC50 = 0.054 nM 10.27 Antagonist activity at progesterone receptor expressed in human T47D cells asses... 17855092
Progesterone receptor IC50 = 0.073 nM 10.14 Antagonist activity at PR in human T47D cells assessed as inhibition of progeste... 30034593
Glucocorticoid receptor Ki = 0.09 nM 10.05 Displacement of fluormone GS Red from human glucocorticoid receptor after 4 hrs ... 28368581
Glucocorticoid receptor Ki = 0.1 nM 10.0 Inhibition of human glucocorticoid receptor 15293993
Progesterone receptor IC50 = 0.1 nM 10.0 Progesterone receptor antagonist activity based on its ability to block progeste... 12419390
Progesterone receptor IC50 = 0.13 nM 9.89 Antagonist activity against progesterone receptor (PR) in an alkaline phosphatas... 12238914
Progesterone receptor IC50 = 0.18 nM 9.74 Antagonistic activity against human progesterone receptor B (hPR-B) in co-transf... 9484511
Progesterone receptor IC50 = 0.18 nM 9.74 Concentration required to give half-maximal inhibition against human Progesteron... 8627601
Progesterone receptor IC50 = 0.2 nM 9.7 Antagonistic activity against Progesterone receptor (PR) in transcriptional acti... 11859003
Progesterone receptor IC50 = 0.2 nM 9.7 Antagonist activity at progesterone receptor in human T47D cells assessed as inh... 20638844
Progesterone receptor IC50 = 0.2 nM 9.7 Inhibition of progesterone receptor mediated progesterone-induced alkaline phosp... 18504132
Progesterone receptor IC50 = 0.2 nM 9.7 Antagonist activity at progesterone receptor assessed as progesterone-induced al... 18722119
Progesterone receptor IC50 = 0.2 nM 9.7 Antagonist activity at human PR expressed in human T47D cells assessed as inhibi... 18318463
Progesterone receptor IC50 = 0.2 nM 9.7 Inhibitory concentration against progesterone stimulated alkaline phosphatase ac... 11591515
Glucocorticoid receptor Ki = 0.24 nM 9.62 Displacement of [3H]DEX from human glucocorticoid receptor 20334371

Literature References

PubMed DOI Target Context # Activities
- 10.6019/CHEMBL3885881 Rattus norvegicus 550
- 10.5281/zenodo.13943903 ADMET 89
16078847 10.1021/jm050205o ADMET 15
22194678 10.1371/journal.pcbi.1002310 Hepatotoxicity 14
30091920 10.1021/acs.jmedchem.8b00743 Glucocorticoid receptor 12
17258455 10.1016/j.bmcl.2006.10.003 Mus musculus 11
15646539 10.1016/s0399-8320(04)95062-2 Unchecked 11
18347111 10.1128/aac.01416-07 Chlamydia pneumoniae 11
30091920 10.1021/acs.jmedchem.8b00743 Androgen receptor 9
29424542 10.1021/acs.jmedchem.7b01690 Glucocorticoid receptor 8
18539027 10.1016/j.bmcl.2008.05.070 Rattus norvegicus 8
15646539 10.1016/s0399-8320(04)95062-2 NON-PROTEIN TARGET 8
16621936 10.1124/dmd.105.006619 ADMET 8
12781198 10.1016/s0960-894x(03)00256-7 Progesterone receptor 7
19734910 10.1038/nchembio.215 Plasmodium falciparum 7
34935393 10.1021/acs.jnatprod.1c01008 Unchecked 6
31274313 10.1021/acs.jmedchem.9b00711 ADMET 6
39240657 10.1021/acs.jmedchem.4c01007 Glucocorticoid receptor 6
17616395 10.1016/j.bmcl.2007.06.066 Glucocorticoid receptor 6
8627601 10.1021/jm950747d Progesterone receptor 6

Data from ChEMBL 36 via Core Engine