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Updated: May 30, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
Structural basis for agonism and antagonism for a set of chemically related progesterone receptor modulators
Scott J Lusher1, Hans C A Raaijmakers, Diep Vu-Pham
1Department of Molecular Design and Informatics, DMPK, MSD, PO Box 20, 5340 BH Oss, The Netherlands. scott.lusher@merck.com
Abstract:
The progesterone receptor is able to bind to a large number and variety of ligands that elicit a broad range of transcriptional responses ranging from full agonism to full antagonism and numerous mixed profiles inbetween. We describe here two new progesterone receptor ligand binding domain x-ray structures bound to compounds from a structurally related but functionally divergent series, which show different binding modes corresponding to their agonistic or antagonistic nature. In addition, we present a third progesterone receptor ligand binding domain dimer bound to an agonist in monomer A and an antagonist in monomer B, which display binding modes in agreement with the earlier observation that agonists and antagonists from this series adopt different binding modes.
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