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Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)

Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depe...

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Autores principales: Chwalisz, Kristof, Garg, Ramesh, Brenner, Robert, Slayden, Ov, Winkel, Craig, Elger, Walter
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1775068/
https://www.ncbi.nlm.nih.gov/pubmed/17118172
http://dx.doi.org/10.1186/1477-7827-4-S1-S8
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author Chwalisz, Kristof
Garg, Ramesh
Brenner, Robert
Slayden, Ov
Winkel, Craig
Elger, Walter
author_facet Chwalisz, Kristof
Garg, Ramesh
Brenner, Robert
Slayden, Ov
Winkel, Craig
Elger, Walter
author_sort Chwalisz, Kristof
collection PubMed
description Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil.
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spelling pubmed-17750682007-01-18 Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs) Chwalisz, Kristof Garg, Ramesh Brenner, Robert Slayden, Ov Winkel, Craig Elger, Walter Reprod Biol Endocrinol Review Selective progesterone receptor modulators (SPRMs) represent a new class of progesterone receptor ligands that exert clinically relevant tissue-selective progesterone agonist, antagonist, partial, or mixed agonist/antagonist effects on various progesterone target tissues in an in vivo situation depending on the biological action studied. The SPRM asoprisnil is being studied in women with symptomatic uterine leiomyomata and endometriosis. Asoprisnil shows a high degree of uterine selectivity as compared to effects on ovulation or ovarian hormone secretion in humans. It induces amenorrhea and decreases leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations. It also has endometrial antiproliferative effects. In pregnant animals, the myometrial, i.e. labor-inducing, effects of asoprisnil are blunted or absent. Studies in non-human primates played a key role during the preclinical development of selective progesterone receptor modulators. These studies provided the first evidence of uterus-selective effects of asoprisnil and structurally related compounds, and the rationale for clinical development of asoprisnil. BioMed Central 2006-10-09 /pmc/articles/PMC1775068/ /pubmed/17118172 http://dx.doi.org/10.1186/1477-7827-4-S1-S8 Text en Copyright © 2006 Chwalisz et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Chwalisz, Kristof
Garg, Ramesh
Brenner, Robert
Slayden, Ov
Winkel, Craig
Elger, Walter
Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)
title Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)
title_full Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)
title_fullStr Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)
title_full_unstemmed Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)
title_short Role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (SPRMs)
title_sort role of nonhuman primate models in the discovery and clinical development of selective progesterone receptor modulators (sprms)
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1775068/
https://www.ncbi.nlm.nih.gov/pubmed/17118172
http://dx.doi.org/10.1186/1477-7827-4-S1-S8
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