title: 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.
authors.affiliation: Departamento de Sistemas Biológicos y de Producción Agrícola y Animal, Universidad Autónoma Metropolitana-Xochimilco , México, D. F. and.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cabeza
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Heuze
authors.forename: Araceli
authors.initials: A
authors.lastname: Sánchez
authors.forename: Mariana
authors.initials: M
authors.lastname: Garrido
authors.forename: Eugene
authors.initials: E
authors.lastname: Bratoeff
mesh_terms: D000107:Acetylation; D018931:Antineoplastic Agents, Hormonal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003687:Dehydroepiandrosterone / Q000737:chemistry; D015195:Drug Design; D005260:Female; D006801:Humans; D006900:Hydroxylation; D011374:Progesterone / Q000737:chemistry; D011372:Progestins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D013739:Testosterone / Q000737:chemistry
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011372:Progestins; D011980:Receptors, Progesterone; D013739:Testosterone; D003687:Dehydroepiandrosterone; D011374:Progesterone
keywords: Androgens; antiprogestins; female cancers; progesterone receptor; progestins