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1TAP Pharmaceutical Products Inc., Lake Forest, Illinois, USA, School of Nursing, Georgetown University, Washington DC, USA Jenapharm GmbH & Co KG, Germany, EnTec GmbH, Hamburg and Jena, Germany
* To whom correspondence should be addressed. E-mail: Kristof.Chwalisz{at}TAP.com.
Selective progesterone receptor modulators (SPRM) represent a new class of progesterone receptor (PR) ligands. SPRMs exert clinically relevant tissue-selective progesterone agonist, antagonist or mixed agonist/antagonist effects on various progesterone target tissues in vivo. Asoprisnil (J867) is the first SPRM to reach an advanced stage of clinical development for the treatment of symptomatic uterine fibroids and endometriosis. Asoprisnil belongs to the class of 11
-benzaldoxime-substituted estratrienes that exhibit partial progesterone agonist/antagonist effects with high PR specificity in animals and humans. Asoprisnil has no antiglucocorticoid activity in humans at therapeutic doses. It exhibits endometrial antiproliferative effects on the endometrium and breast in primates. Unlike progesterone antagonists, asoprisnil does not induce labor in relevant models of pregnancy and parturition. It induces amenorrhea primarily by targeting the endometrium. In human subjects with uterine fibroids, asoprisnil suppressed both the duration and intensity of uterine bleeding in a dose-dependent manner and reduced tumor volume in the absence of estrogen deprivation. In subjects with endometriosis, asoprisnil was effective in reducing non-menstrual pain and dysmenorrhea. Asoprisnil may, therefore, provide a novel, tissue-selective approach to control endometriosis-related pain. SPRMs have the potential to become a novel treatment of uterine fibroids and endometriosis.
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