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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Bibliographic Details
Published in:Reproductive biology and endocrinology 2006-10, Vol.4 Suppl 1 (S1), p.S8-S8, Article S8
Main Authors: Chwalisz, Kristof, Garg, Ramesh, Brenner, Robert, Slayden, Ov, Winkel, Craig, Elger, Walter
Format: Article
Language:English
Subjects:
Animals
Drug Evaluation, Preclinical
Endometrium - drug effects
Estrenes - chemistry
Estrenes - pharmacology
Female
Humans
Leiomyoma - drug therapy
Mammary Glands, Animal - drug effects
Models, Animal
Models, Biological
Models, Molecular
Organ Specificity
Oximes - chemistry
Oximes - pharmacology
Primates - physiology
Progesterone Congeners - chemical synthesis
Progesterone Congeners - pharmacology
Progesterone Congeners - therapeutic use
Receptors, Progesterone - agonists
Receptors, Progesterone - antagonists & inhibitors
Receptors, Progesterone - metabolism
Review
Uterine Hemorrhage - drug therapy
Uterine Neoplasms - drug therapy
Uterus - drug effects
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Summary: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.
ISSN:1477-7827
1477-7827
DOI:10.1186/1477-7827-4-s1-s8