Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity

  title={Nonsteroidal progesterone receptor ligands with unprecedented receptor selectivity},
  author={Stephen S. Palmer and Carolyn A. Campen and George F. Allan and Philip J. Rybczynski and Donna Haynes-Johnson and Amy Hutchins and Patricia J Kraft and Margaret Kiddoe and Muh-Tsann Lai and Elizabeth Lombardi and Phyllis Pedersen and Gary D. Hodgen and Donald W. Combs},
  journal={The Journal of Steroid Biochemistry and Molecular Biology},
  • S. PalmerC. Campen D. Combs
  • Published 1 December 2000
  • Biology
  • The Journal of Steroid Biochemistry and Molecular Biology

Pharmacology and clinical use of sex steroid hormone receptor modulators.

How the experience gained from the classical pharmacology of these receptors and their molecular similarities led to new options for the treatment of gender-specific diseases are discussed and recent progress in medicinal chemistry of sex hormone-modulating drugs is highlighted.

The evolution of progesterone receptor ligands

Ligands for PR were developed into drugs, and their evolution can be crudely divided into three periods: drug‐like steroids that mimic the gestational properties of progesterone; drug-like steroids with different properties from progester one and expanded therapeutic applications; and non‐steroidal PR ligands with improved selectivity and modulator properties and further expand therapeutic applications.



Nonsteroidal progesterone receptor ligands. 2. High-affinity ligands with selectivity for bone cell progesterone receptors.

A novel series of nonsteroidal heterocycles was discovered which display cell-type selective, high-affinity (nanomolar) binding to the progesterone receptors from TE85 osteosarcoma cells but > 1

Synthesis and biological activity of novel nonsteroidal progesterone receptor antagonists based on cyclocymopol monomethyl ether.

A novel class of nonsteroidal progesterone receptor antagonists has been synthesized and was shown to exhibit moderate binding affinity for hPR-A, the ability to inhibit the transcriptional activity

Discovery and preliminary SAR studies of a novel, nonsteroidal progesterone receptor antagonist pharmacophore.

Two compounds, 10 and 11 with potencies comparable or equal to the steroidal hPR antagonist onapristone, were demonstrated to act as antiprogestins in vivo after oral administration to rodents, the first disclosure of orally active nonsteroidal antip rogestins.

Novel ligands of steroid hormone receptors

The development of novel ligands for steroid hormone receptors has become a burgeoning field with tremendous potential in numerous human therapies, and these compounds will likely grow into complementary pharmacophores of defined function and enhanced therapeutic utility.

Human progesterone receptor complexed with the antagonist RU 486 binds to hormone response elements in a structurally altered form.

Results indicate that human PR transformed by RU 486 exhibit no impairment in binding to specific DNA sites of target genes, but when bound to DNA assumes a structural form different from that of the receptor-agonist complexes to activate transcription, which does not permit protein-protein interactions required for receptor-mediated induction of gene transcription.

Induction of a novel conformation in the progesterone receptor by ZK299 involves a defined region of the carboxyl-terminal tail.

The results suggest that multiple types of antiprogestin can be defined in terms of their effects on the conformation of the carboxyl-terminal activation function of the progesterone receptor.