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Progesterone is more than a progestin. Beyond functions in cycle and pregnancy, progesterone binds with high affinity to the mineralocorticoid receptor (MR) acting as an antagonist, with obvious significance for electrolyte homeostasis, an array of MR-related functions in the circulation as well as in the CNS. Progesterone induces natriuresis at(More)
Fluorescence resonance energy transfer (FRET) provides information on the distance between a donor and an acceptor dye in the range 10 to 100 A. Knowledge of the exact positions of some dyes with respect to nucleic acids now enables us to translate these data into precise structural information using molecular modeling. Advances in the preparation of(More)
Advances in bioinformatics and protein modeling algorithms, in addition to the enormous increase in experimental protein structure information, have aided in the generation of databases that comprise homology models of a significant portion of known genomic protein sequences. Currently, 3D structure information can be generated for up to 56% of all known(More)
Drug-like and lead-like hits derived from HTS campaigns provide good starting points for lead optimization. However, too strong emphasis on potency as hit-selection parameter might hamper the success of such projects. A detailed absorption, distribution, metabolism, excretion and toxicology (ADME-Tox) profiling is needed to help identify hits with a minimum(More)
Other isotype-selective estrogen receptor (ER) agonists, the selective ERalpha agonist 3,17-dihydroxy-19-nor-17alpha-pregna-1,3,5 (10)-triene-21,16alpha-lactone and the selective ERbeta agonist 8-vinylestra-1,3,5 (10)-triene-3,17beta-diol, were used in hypophysectomized rats, gonadotropin-releasing hormone antagonist-treated mice, as well as intact rats to(More)
Several clinical candidates have now emerged as a result of an intense search for orally available, antithrombotic factor Xa inhibitors. This review highlights the discovery of XareltoTM (Rivaroxaban) starting from an initial tetrahydrophthalimide screening hit. The major breakthrough was the finding that a chlorothiophene moiety can undergo an interaction(More)
Aldosterone is a hormone that exerts manifold deleterious effects on the kidneys, blood vessels, and heart which can lead to pathophysiological consequences. Inhibition of the mineralocorticoid receptor (MR) is a proven therapeutic concept for the management of associated diseases. Use of the currently marketed MR antagonists spironolactone and eplerenone(More)
Proteases play a key role in cellular biology and have become priority targets for new pharmaceuticals. Thus, there is a high demand for specific, sensitive, and quick assays to monitor the activity of endoproteases. We designed affinity-tagged helical proteins with unique protease cleavage sites and thus constructed universal, molecularly defined, and(More)