Recent advances in structure of progestins and their binding to progesterone receptors

Abstract

The role of progesterone in women’s cancers as well as the knowledge of the progesterone receptor (PR) structure has prompted the design of different therapies. The aim of this review is to describe the basic structure of PR agonists and antagonists as well as the recent treatments for illness associated with the progesterone receptor. The rational design for potent and effective drugs for the treatment of female cancer must consider the structural changes of the androgen and progestogen skeleton which are an indicator of their activity as progestins or antiprogestins. The presence of a hydroxyl group at C-17 in the progesterone skeleton brings about a loss of progestational activity whereas acetylation induces a progestational effect. The incorporation of an ethynyl functional group to the testosterone framework results in a loss of androgenic activity with a concomitant enhancement of the progestational effect. On the other hand, an ester function at C-3 of dehydroepiandrosterone skeleton induces partial antagonism to the PR.

• Androgens
• antiprogestins
• female cancers
• progestins
• progesterone receptor

Declaration of interest

This manuscript represents an original, unpublished material not under editorial consideration elsewhere following ethical guidelines in the conduct of the research. This paper was written also, according to the authors guide and do not have any conflict of interest. This study was supported by a Grant from Consejo Nacional de Ciencia y Tecnología (project number 54853) and DGAPA (project number IN211312).