Tanaproget is a novel agonist of progesterone receptor with IC50 of 1.7 nM [1].
Progesterone receptor (PR) is a member of the nuclear receptor superfamily and binding of progesterone causes PR conformational changes, which then changing gene expression. Progesterone plays an important role in female reproduction [1].
In T47D cells, tanaproget caused alkaline phosphatase activity with EC50 value of 0.1 nM. In a mammalian two-hybrid assay, tanaproget showed 50-fold more potent than progesterone. In stromal cells isolated from endometrial, tanaproget (1 nM) significantly suppressed pro-MMP-3 secretion. Also, Tanaproget effectively prevented pro-MMP-3 secretion through IL-1α-mediated stimulation [2].
In endometriosis mice model with human lesions growing on the parietal peritoneum of mice, tanaproget completely regressed human lesions in 58% treated animals. Also, the lesions were smaller and fewer compared with the lesions in placebo-treated mice at the end of therapy [2]. In healthy women, the elimination half-life (t(1/2)) of tanaproget ranged from 12 to 30 h. Tanaproget reduced cervical mucus scores, which suggesting poor production and quality of cervical mucus [3].
References:
[1]. Zhang Z, Olland AM, Zhu Y, et al. Molecular and pharmacological properties of a potent and selective novel nonsteroidal progesterone receptor agonist tanaproget. J Biol Chem, 2005, 280(31): 28468-28475.
[2]. Bruner-Tran KL, Zhang Z, Eisenberg E, et al. Down-regulation of endometrial matrix metalloproteinase-3 and -7 expression in vitro and therapeutic regression of experimental endometriosis in vivo by a novel nonsteroidal progesterone receptor agonist, tanaproget. J Clin Endocrinol Metab, 2006, 91(4): 1554-1560.
[3]. Bapst JL, Ermer JC, Ferron GM, et al. Pharmacokinetics and safety of tanaproget, a nonsteroidal progesterone receptor agonist, in healthy women. Contraception, 2006, 74(5): 414-418.