Gestrinone

Gestrinone (R2323) is a synthetic steroid hormone used to treat endometriosis. It inhibits leiomyoma cells with an IC₅₀ of 43.67 μM. Gestrinone is a click chemistry reagent, itcontains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups. IC50 & Target: IC50: 43.67 μM (leiomyoma cells)^[2] In Vitro: Gestrinone binds to endometrial receptors for estrogen, progesterone and androgen, occupies all specific binding sites of steroids in the steroid target cells despite the presence of endogenous steroids^[1]. Gestrinone exhibits stronger inhibitory effects on the growth of leiomyoma cells at 60 h than that at 20 and 40 h. Leiomyoma cells appears less dense, the cytoplasm is atrophic, the intercellular connections dwindled and nuclear aggregations are observed with more than 10 μM gestrinone treatment. Gestrinone treatment reduces the relative mRNA levels of estrogen α in a concentration dependent manner at concentrations of 0.1-3.0 μM^[2]. In Vivo: The estrogen-sensitive endpoints, vaginal keratinization and uterine progesterone receptor concentration, are enhanced by treatment with a combination of flutamide and either danazol or gestrinone. These data indicate that danazol and gestrinone have estrogenic activity that is masked by the androgenic component of these drugs^[3]. The mean hormone binding globulin treated with gestrinone fell from 56.4 nM to 28.1 nM after one week’s treatment and to 7.1 nM after 4 weeks respectively^[4].