Exploring the Potential of BAY 1002670: A Promising Progesterone Receptor Modulator in Gynecological Treatments

The study investigates the potential of BAY 1002670, a new progesterone receptor (PR) modulator, as a treatment for uterine fibroids. BAY 1002670 has shown to be highly potent and selective in in vitro and in vivo assays, demonstrating significant efficacy in a humanized fibroid disease model, which makes it a promising candidate for treating uterine fibroids.

Despite the known clinical utility of PR inhibiting ligands and the development of PR antagonists over 30 years ago, no such compound has been approved for long-term use due to suboptimal selectivity and safety profiles.

The preclinical studies conducted included in vitro and in vivo assays to evaluate the properties of BAY 1002670 and a fibroid xenograft study to directly assess its efficacy on human target tissue. The compound was tested for binding and transactivational activity on various human steroid receptors and its activity in rat and rabbit models. It was also tested in a uterine fibroid disease model using primary human tumor tissues as xenografts in immunodeficient mice under estradiol (E2) and progesterone (P) treatment.

BAY 1002670 displayed highly selective binding and antagonistic activity for the PR at subnanomolar concentrations. It showed favorable selectivity towards other nuclear hormone receptors with no in vivo activity observed at glucocorticoid, estrogenic, and mineralocorticoid receptors, and only weak anti-androgenic activity. In the human fibroid xenograft model, it induced a marked dose-dependent reduction, achieving a 95% reduction in fibroid tumor weight gain at a dose of 3 mg/kg/day (P < 0.005).

However, the study's limitations include that the selectivity and potency of BAY 1002670 have only been determined in vitro and in animal models. The findings suggest that BAY 1002670 could be a treatment option not only for uterine fibroids but also for other gynecological conditions.

The research was conducted at Bayer Pharma AG, and all authors are employees of the company, with no external funding reported.