tcsc1157 Ulipristal (acetate)

Ulipristal (acetate) is a novel selective progesterone receptor modulator (SPRM) for the treatment of benign gynecological conditions such as uterine myoma.

In Vitro: Ulipristal acetate blocks activin A modulation of fibronectin and vascular endothelial growth factor A (VEGF-A) mRNA expression in cultured myometrial and leiomyoma cells^[2]. Ulipristal acetate decreases the DNA fragmentation at the 100-ng/mL dose and continuing up to the 10,000-ng/mL dose compared to those spermatozoa in the control group^[3].

In Vivo: Ulipristal and CDB-4124 have significant antiprogestational activity in vivo^[1]. Ulipristal acetate decreases incidences of fibroadenomas and adenocarcinomas in the mammary gland in all treated groups. Ulipristal acetate exposure [AUC(0-24h)] at the highest dose in rats is 67 times human therapeutic exposure at 10 mg/day. In mice, no tumor of any type increases at Ulipristal acetate exposures up to 313 times of therapeutic exposure. Ulipristal acetate-related findings in mice are limited to organ weight changes in the liver, pituitary, thyroid/parathyroid glands, and epididymis as well as minimal panlobular hepatocellular hypertrophy in male and female mice receiving 130 mg/kg/day^[4]. Ulipristal acetate (1 mg/kg and 5 mg/kg) increases the frequency with which pathologists assessed the endometrium as being thickened compared to controls in a dose-dependent manner. There is a slight decrease in secretory differentiation with increasing dose of Ulipristal acetate, with small decreases in frequency of sub- and supra-nuclear vacuolation^[5].