ChemInform Abstract: Discovery and Preliminary SAR Studies of a Novel, Nonsteroidal Progesterone Receptor Antagonist Pharmacophore.

ChemInform ◽  
2010 ◽  
Vol 29 (51) ◽  
pp. no-no
Author(s):  
C. L. F. POOLEY ◽  
J. P. EDWARDS ◽  
M. E. GOLDMAN ◽  
M.-W. WANG ◽  
K. B. MARSCHKE ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Sar Studies

Discovery and Preliminary SAR Studies of a Novel, Nonsteroidal Progesterone Receptor Antagonist Pharmacophore

1998 ◽  
Vol 41 (18) ◽  
pp. 3461-3466 ◽  
Author(s):  
Charlotte L. F. Pooley ◽  
James P. Edwards ◽  
Mark E. Goldman ◽  
Ming-Wei Wang ◽  
Keith B. Marschke ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Sar Studies

scholarly journals Progesterone receptor antagonist provides palliative effects for uterine leiomyoma through a Bcl-2/Beclin1-dependent mechanism

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Lindong Zhang ◽  
Quanling Feng ◽  
Zhiting Wang ◽  
Pingping Liu ◽  
Shihong Cui
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Uterine Leiomyoma ◽  
Lentiviral Vector ◽  
Smooth Muscle Tumor ◽  
Reproductive Age ◽  
M Cells ◽  
Promising Therapeutic Target ◽  
Dependent Mechanism

Abstract Uterine leiomyoma is the most common benign smooth muscle tumor of uterus in women of reproductive age, with a high lifetime incidence. Nowadays, the exploration on the pharmacotherapies, such as progesterone receptor antagonist (PRA) requires more attention. Hence, the current study aimed to examine whether mifepristone, a PRA, influences the autophagy and apoptosis of uterine leiomyoma cells. Primary uterine leiomyoma cells were collected from 36 patients diagnosed with uterine leiomyoma to establish PR-M-positive (PR-M[+]) cells. The lentiviral vector overexpressing or silencing PR-M was subsequently delivered into one part of PR-M(+) cells in order to evaluate the role of PR-M in PR-M(+) cells. The results obtained revealed that cell viability was increased, while cell autophagy and apoptosis were diminished in the PR-M(+) cells treated with overexpressed PR-M, whereby the Bcl-2 level was elevated and the level of Beclin1 was reduced. An opposite trends were identified following treatment with knockdown of PR-M. Mifepristone at different concentrations (low, moderate, or high) was then applied to treat another part of the PR-M(+) cells. Mifepristone was identified to promote cell autophagy and apoptosis, decrease Bcl-2 level and increase Beclin1 level, accompanied by weakened interaction between Bcl-2 and Beclin1. Moreover, these effects of mifepristone on PR-M(+) cells were enhanced with increasing of the concentration. Taken together, the present study present evidence indicates the ability of PRA to regulate the Bcl-2/Beclin1 axis, ultimately promoting the autophagy and apoptosis of uterine leiomyoma cells, highlighting that PRA serves as a promising therapeutic target for the treatment of uterine leiomyoma.

Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer

1999 ◽  
Vol 35 (2) ◽  
pp. 214-218 ◽  
Author(s):  
J.F.R Robertson ◽  
P.C Willsher ◽  
L Winterbottom ◽  
R.W Blamey ◽  
S Thorpe
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Primary Breast Cancer ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy

Nuclear progesterone receptor isoforms and their functions in the female reproductive tract

2011 ◽  
Vol 14 (1) ◽  
pp. 149-158 ◽  
Author(s):  
R. Rękawiecki ◽  
M. Kowalik ◽  
J. Kotwica
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Reproductive System ◽  
Reproductive Tract ◽  
Physiological Effect ◽  
Female Reproductive Tract ◽  
Target Cells ◽  
Progesterone Receptor Isoforms ◽  
Receptor Isoforms ◽  
Nuclear Progesterone Receptor

Nuclear progesterone receptor isoforms and their functions in the female reproductive tract Progesterone (P4), which is produced by the corpus luteum (CL), creates proper conditions for the embryo implantation, its development, and ensures proper conditions for the duration of pregnancy. Besides the non-genomic activity of P4 on target cells, its main physiological effect is caused through genomic action by the progesterone nuclear receptor (PGR). This nuclear progesterone receptor occurs in two specific isoforms, PGRA and PGRB. PGRA isoform acts as an inhibitor of transcriptional action of PGRB. The inactive receptor is connected with chaperone proteins and attachment of P4 causes disconnection of chaperones and unveiling of DNA binding domain (DBD). After receptor dimerization in the cells' nucleus and interaction with hormone response element (HRE), the receptor coactivators are connected and transcription is initiated. The ratio of these isoforms changes during the estrous cycle and reflects the different levels of P4 effect on the reproductive system. Both isoforms, PGRA and PGRB, also show a different response to the P4 receptor antagonist activity. Connection of the antagonist to PGRA can block PGRB, but acting through the PGRB isoform, P4 receptor antagonist may undergo conversion to a strongly receptor agonist. A third isoform, PGRC, has also been revealed. This isoform is the shortest and does not have transcriptional activity. Alternative splicing and insertion of additional exons may lead to the formation of different PGR isoforms. This paper summarizes the available data on the progesterone receptor isoforms and its regulatory action within the female reproductive system.

A Novel, High-Affinity, Fluorescent Progesterone Receptor Antagonist. Synthesis and in Vitro Studies

2004 ◽  
Vol 15 (2) ◽  
pp. 359-365 ◽  
Author(s):  
Claudia Hödl ◽  
Wolfgang S. L. Strauss ◽  
Reinhard Sailer ◽  
Christoph Seger ◽  
Rudolf Steiner ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
In Vitro Studies ◽  
High Affinity

Termination of mid-gestation pregnancy in bitches with aglepristone, a progesterone receptor antagonist

2000 ◽  
Vol 53 (4) ◽  
pp. 941-950 ◽  
Author(s):  
S. Galac ◽  
H.S. Kooistra ◽  
J. Butinar ◽  
M.M. Bevers ◽  
S.J. Dieleman ◽  
...  
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist

Treatment of growth hormone excess in dogs with the progesterone receptor antagonist aglépristone

2006 ◽  
Vol 66 (4) ◽  
pp. 797-803 ◽  
Author(s):  
S.F.M. Bhatti ◽  
L. Duchateau ◽  
A.C. Okkens ◽  
L.M.L. Van Ham ◽  
J.A. Mol ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Progesterone Receptor ◽  
Receptor Antagonist

Effect of the antiprogestin RU486 on uterine sensitivity to oxytocin in ewes in late pregnancy

1992 ◽  
Vol 134 (3) ◽  
pp. 353-360 ◽  
Author(s):  
K. M. Burgess ◽  
G. Jenkin ◽  
M. M. Ralph ◽  
G. D. Thorburn
Keyword(s):  
Progesterone Receptor ◽  
Receptor Antagonist ◽  
Uterine Artery ◽  
Area Under The Curve ◽  
Late Pregnancy ◽  
Peak Height ◽  
Uterine Horn ◽  
Pregnant Sheep ◽  
Pg Release

ABSTRACT The effect of RU486, a synthetic progesterone receptor antagonist, on basal uterine prostaglandin (PG) release and release in response to oxytocin injection has been investigated in late-pregnant sheep (days 135–140 of gestation). Fifteen hours after i.m. injection of RU486 (50 mg; n = 5) or vehicle alone (n = 4), bolus injections of oxytocin (50, 500 and 5000 mU) were administered via a uterine artery ipsilateral to the pregnant uterine horn at 2-hourly intervals. Uteroovarian vein concentrations of 13,14-dihydro-15-keto PGF2α (PGFM) and PGE2 were determined before and during oxytocin stimulation. Basal concentrations of both PGFM and PGE2 were significantly (P < 0·001) increased in ewes 15 h after RU486 administration compared with ewes receiving vehicle alone. Concentrations of PGFM, but not PGE2, increased significantly (P < 0·001) following injection of each dose of oxytocin in both treated and untreated animals. The response to oxytocin, measured both as the area under the curve and as the peak height of PGFM release, was significantly (P <0·05) greater in RU486-treated ewes. There was no significant effect of oxytocin on the area or peak height of PGE2 response in either RU486-treated or control animals. These results demonstrate that treatment of late-pregnant ewes with RU486 results in an increase in basal uterine PGFM and PGE2 as well as oxytocin-stimulated PGFM release. Journal of Endocrinology (1992) 134, 353–360

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