Olaf Nimz

TL;DR: Three X-ray structures of three different agonists bound to the ligand binding domain of LXRalpha are presented, and a model for allosteric activation in nuclear receptor dimers is proposed, in which an unactivated RXR partner provides an inhibitory tail wrap to the cofactor binding pocket of NXR.

TL;DR: 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.

TL;DR: Optimization of a water soluble, moderately potent lead series of isoxazole-3-carboxamides was conducted, affording a compound with the requisite balance of potency, solubility and physicochemical properties for in vivo use.

TL;DR: Systematic optimisation of a poorly soluble lead series of isoxazole-3-carboxamides was conducted and substitution of the 4-position with specific polar functionality afforded the requisite balance of potency, solubility and physicochemical properties.

TL;DR: High-throughput screening of 3.87 million compounds delivered a novel series of non-steroidal GR antagonists that allowed progression from a non-selective ligand with a poor ADMET profile to an orally bioavailable, selective, stable, glucocorticoid receptor antagonist.