"目錄號: HY-13683
OthersGPCR/G ProteinAutophagy-
Mifepristone 是一種孕激素受體 (progesterone receptor吊奢，PR) 拮抗劑民逼，T47D 細(xì)胞檢測中，IC50為 0.2 nM恋昼，Mifepristone也是一種糖皮質(zhì)激素受體(glucocorticoid receptor顶瞳，GR)拮抗劑玖姑，在 A549 細(xì)胞檢測中愕秫，IC50為 2.6 nM。
Progesterone ReceptorGlucocorticoid ReceptorAutophagy
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生物活性
Description
Mifepristone is aprogesterone receptor(PR) antagonist (IC50=0.2 nM) in a T47D cell-based assay, also is aglucocorticoid receptor(GR) antagonist (IC50=2.6 nM) in an A549 cell-based assay.
IC50& Target
IC50: 0.2 nM (progesterone receptor, in T47D cells), 2.6 nM (glucocorticoid receptor, in A549 cells)[1]
In Vitro
The discovery of the first competitive progesterone antagonist, Mifepristone, has stimulated an intense search for more potent and more selective antiprogestins[1]. Cell growth is evaluated after 4 days of exposure to Mifepristone at 10 μM, a concentration close to the plasma concentration achievable in humans. The antiproliferative effect of Cisplatin is potentiated when administered in combination with Mifepristone in HeLa cells. The IC50of Cisplatin in combination with Mifepristone is lower (14.2 μM) than that of Cisplatin alone (34.2 μM) in HeLa cells with an approximately 2.5-fold difference. After treatment with Mifepristone, the accumulation of intracellular Cisplatin in HeLa cells is 2-fold greater, representing a significant difference (p=0.009), compare with Cisplatin alone from 0.79 to 1.52 μg/mg of protein[2].
In Vivo
The cervix tumor xenograft models are treated with Cisplatin alone, there is a tumor growth inhibition compare with control group. However, the tumor weight loss is even more significant (p<0.05) with the combination of Cisplatin and Mifepristone at the doses used, showing a decrease of ~50% compared with the treatments alone by the end of the study[2]. Adult male Sprague-Dawley rats are subjected to a 4-day binge-like EtOH administration regimen (3 to 5 g/kg/i.g. every 8 hours designed to produce peak blood EtOH levels (BELs) of <300 mg/dL). Subgroups of animals receive s.c. injection of Mifepristone (20 or 40 mg/kg in peanut oil). Although Mifepristone produces no significant changes in behavior of EtOH-na?ve animals, pretreatment with Mifepristone (40 mg/kg) significantly reducesthe severity of EtOH withdrawal. Asignificant interaction between diet and drug, F(5,55)=3.92, p<0.05, such that EtOH-treated animals receiving vehicle or 20 mg/kg of Mifepristone displayssignificantly more signs of EtOH withdrawal than does EtOH-na?ve animals receiving the same drug treatment. Importantly, treatment with 40 mg/kg of Mifepristone significantly reduces the severity of EtOH withdrawal, in a dose-dependent manner[3].
Clinical Trial
Gynuity Health Projects
Termination of Pregnancy
April 2013
New Mexico Cancer Care Alliance-The Feminist Majority Foundation
Cancer
November 2008
University of Southern California
Cervical Prostaglandin EP3 Receptors-Pregnancy
September 2004
Mediterranea Medica S. L.
Uterine Fibroids
January 2007
Phase 2-Phase 3
Corcept Therapeutics
Cushing's Syndrome
July 2009
Phase 3
Icahn School of Medicine at Mount Sinai
Mild Hypercortisolism
November 2013
Phase 4
Dana-Farber Cancer Institute-Beth Israel Deaconess Medical Center-Massachusetts General Hospital-Brigham and Women's Hospital-Georgetown University
Prostate Cancer-Adenocarcinoma of Prostate
February 2005
Phase 2
Check, Jerome H., M.D., Ph.D.-Corcept Therapeutics
Non-Small Cell Lung Cancer (NSCLC)
December 2015
Phase 2
Mediterranea Medica S. L.
Uterine Fibroids
May 2008
Phase 2-Phase 3
Boston University-Society of Family Planning
Induced Abortion-Abortion Techniques-Mifepristone-Misoprostol
June 2012
Mediterranea Medica S. L.
Uterine Fibroids
March 2010
Phase 2-Phase 3
Corcept Therapeutics-Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Cushing's Disease
August 2013
Phase 3
Gynuity Health Projects-Hopital La Rabta
Abortion, 3 Months
July 2014
Phase 4
University of Pittsburgh
Anembryonic Pregnancy-Gestation Abnormality-Intrauterine Fetal Demise Term
January 2005
Phase 4
University of Rochester-Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Leiomyoma
July 2003
Phase 3
Corcept Therapeutics
Psychotic Depression-Severe Major Depression With Psychotic Features-Psychosis
March 2008
Phase 3
Hospital Provincial Magdalena V. de Martínez-Agencia Nacional de Promoción de Ciencia y Tecnología, MINCYT-Instituto de Biología y Medicina Experimental (IBYME-CONICET)
Breast Cancer
April 2016
New York State Psychiatric Institute
Cocaine Dependence
May 2010
Phase 2-Phase 3
M.D. Anderson Cancer Center
Endometrial Cancer
September 2001
Phase 2
Gynuity Health Projects
Menstrual Regulation
November 2012
Phase 4
Corcept Therapeutics
Cushing's Disease-Cushing's Syndrome
November 2010
Phase 3
Montefiore Medical Center
Intrauterine Fetal Demise-Fetal Death
February 2016
Phase 4
Corcept Therapeutics
Breast Cancer-Ovarian Epithelial Cancer Recurrent-Sarcoma-Non-small Cell Lung Cancer-Carcinoma, Transitional Cell-Prostate Cancer-Prostatic Neoplasms
January 2014
Phase 1
Gynuity Health Projects
Abortion, First Trimester
September 2006
Gynuity Health Projects
Termination of Pregnancy
May 2009
BioPro Medical Ltd
Uterine Fibroid-Vaginal Bleeding.
April 2009
Phase 2
China Resources Zizhu Pharmaceutical Co., Ltd.
Uterine Fibroid
June 1, 2017
Phase 4
Stanford University
Depression
January 2003
Charles Drew University of Medicine and Science
Type 2 Diabetes Mellitus-Insulin Resistance
February 3, 2017
Phase 2
Stanford University
Depression
January 2003
Corcept Therapeutics
Healthy Subjects
September 2008
Phase 1
Gynuity Health Projects
Complete Uterine Evacuation After Use of Study Drugs
February 2013
Phase 4
Southwest Oncology Group-National Cancer Institute (NCI)
Meningioma
August 1992
Phase 3
VA Office of Research and Development
Stress Disorders, Post-Traumatic
November 19, 2012
Phase 2
Corcept Therapeutics
Depressive Disorder, Major
May 2005
Phase 3
Corcept Therapeutics
Major Depressive Disorder-Psychotic Disorders
August 2005
Phase 3
Eric Lenze-Washington University School of Medicine
Anxiety Disorders
September 2012
Phase 1-Phase 2
University of Chicago
Advanced HER2-negative Breast Cancer
September 2017
Phase 2
University of British Columbia-Western Economic Diversification Canada-Stanley Medical Research Institute
Bipolar Depression
July 2006
Phase 2
Gynuity Health Projects-University of Puerto Rico
Abortion, Induced
February 2011
Phase 3
Gynuity Health Projects
Abortion, Induced
June 2009
University of California, San Diego
Invasive Breast Cancer-Ductal Carcinoma in Situ
June 2010
Early Phase 1
Gynuity Health Projects
Missed Abortion-Pregnancy
January 2015
Phase 4
