Nuclear Receptors as Targets for Drug Design: New Options and Old Challenges

摘要: Steroid receptors, a subgroup of the superfamily nuclear receptors (Gronemeyer and Laudet 1995), have been target for pharmacological drug design since their recognition as “master genes” with pleiotropic action on various physiological processes (for review see De Groot 1995). All (NRs) are transcription factors regulating specific gene programs in response to binding cognate ligands through alteration of: (a) activity basal machinery, (b) chromatin structure at genes (Fig. 1). In addi-tion this “direct” action, NRs can also mutually interfere, positively or negatively, number other signaling (a poorly understood phenomenon, often referred “signal transduction crosstalk”; Fig. Finally, is increasingly recognized, themselves be targets pathways modified post-transcriptionally sites, thereby modulating receptor activity.