Disease relevance of Asoprisnil

• 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 [1].
• In subjects with endometriosis, asoprisnil was effective in reducing nonmenstrual pain and dysmenorrhea [1].
• Unlike progestins, asoprisnil does not induce breakthrough bleeding [2].
• Thus, asoprisnil has the potential to target the major clinical symptoms of leiomyomata related to both menorrhagia and the size of the tumors and may, therefore, reduce or eliminate the need for surgery [3].

High impact information on Asoprisnil

• Asoprisnil (J867) is the first SPRM to reach an advanced stage of clinical development for the treatment of symptomatic uterine fibroids and endometriosis [1].
• Asoprisnil belongs to the class of 11beta-benzaldoxime-substituted estratrienes that exhibit partial progesterone agonist/antagonist effects with high progesterone receptor specificity in animals and humans [1].
• Unlike progesterone antagonists, asoprisnil does not induce labor in relevant models of pregnancy and parturition [1].
• RESULTS: Compared with untreated cultures, asoprisnil decreased the number of viable cultured cells, the PCNA-positive rate, and PCNA protein expression in cultured leiomyoma cells [4].
• In cultured myometrial cells, however, asoprisnil did not affect cell proliferation and apoptosis [4].

Chemical compound and disease context of Asoprisnil

• CONTEXT: Asoprisnil, a selective progesterone (P4) receptor (PR) modulator (SPRM) with mixed P4 agonist/antagonist activities, reduces uterine leiomyoma volume in a dose-dependent manner in the presence of follicular phase estrogen concentrations [4].

Biological context of Asoprisnil

• CONCLUSIONS: These results show that asoprisnil inhibits proliferation and induces apoptosis in cultured uterine leiomyoma cells in the absence of comparable effects on cultured normal myometrial cells, suggesting a cell type-specific effect [4].
• RESULTS: Asoprisnil consistently prolonged the menstrual cycle at doses > or = 10 mg QD [5].
• Early clinical studies of asoprisnil in normal volunteers demonstrated a dose-dependent suppression of menstruation irrespective of the effects on ovulation, with no change in basal estrogen concentrations and no antiglucocorticoid effects [2].
• Asoprisnil exhibits only marginal antiglucocorticoid activity in transactivation in vitro assays and animal models [2].
• CONCLUSIONS: Asoprisnil reversibly suppressed menstruation at doses > or = 10 mg QD irrespective of the effect on luteal phase progesterone concentrations indicative of luteinization [5].

Anatomical context of Asoprisnil

• In the rabbit endometrium, both asoprisnil and J912 induce partial agonist and antagonist effects [2].

Gene context of Asoprisnil

• Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy [2].
• RESULTS: Treatment with 10(-7) M asoprisnil decreased EGF, IGF-I and TGFbeta3 mRNA and protein expression as well as p-EGFR, IGF-IRalpha and p-TGFbeta RII protein expression in leiomyoma cells cultured for 72 h [6].
• OBJECTIVE AND METHODS: The present study evaluated the effects of asoprisnil on cell proliferation, the expression of apoptosis-related proteins, and apoptosis in cultured human uterine leiomyoma cells and matched normal myometrial cells [4].
• Asoprisnil increased the TUNEL-positive rate, cleaved caspase-3, and cleaved poly(adenosine 5'-diphosphate-ribose) polymerase expression and decreased Bcl-2 protein expression in cultured leiomyoma cells [4].
• Therapeutic potential for the selective progesterone receptor modulator asoprisnil in the treatment of leiomyomata [3].

References