Overview of nomenclature of nuclear receptors.

@article{citeulike:2254243, abstract = {Nuclear receptor pharmacology has, to a certain extent, led the way, compared with other receptor systems, in the appreciation that ligands may exert very diverse pharmacology, based on their individual chemical structure and the allosteric changes induced in the receptor/accessory protein complex. This can lead to very selective pharmacological effects, which may not necessarily be predicted from the experience with other agonists/partial agonists/antagonists. If this is the case, then drug discovery may be back to drug-specific pharmacology (where each drug may have an original profile), rather than specific-drug pharmacology (where agents specific for a receptor have a distinct profile). As functional selectivity is indeed a crucial mechanism to be considered when going through the drug discovery development process, then initial screens using reconstituted systems may not show the appropriate pharmacology, simply because the required stoichiometry of corepressors and coactivators may not be present to select the best compounds; therefore, multiple effector systems are necessary to screen for differential activation, and, even then, screening with in vivo pathophysiological models may ultimately be required for the selection process-a massive but necessary task for pharmacologists. Thus, the characterization of nuclear receptors and their associated proteins and the ligands that interact with them will remain a challenge to pharmacologists.}, address = {Department of Cell Biology and Signal Transduction, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France. germain@titus.u-strasbg.fr}, author = {Germain, P. and Staels, B. and Dacquet, C. and Spedding, M. and Laudet, V. }, citeulike-article-id = {2254243}, doi = {10.1124/pr.58.4.2}, issn = {0031-6997}, journal = {Pharmacol Rev}, keywords = {nuclear, receptor, review}, month = {December}, number = {4}, pages = {685--704}, posted-at = {2008-01-18 22:10:55}, priority = {2}, title = {Overview of nomenclature of nuclear receptors.}, url = {http://dx.doi.org/10.1124/pr.58.4.2}, volume = {58}, year = {2006} }

TY - JOUR ID - citeulike:2254243 L3 - citeulike-article-id:2254243 TI - Overview of nomenclature of nuclear receptors. JF - Pharmacol Rev VL - 58 IS - 4 SP - 685 EP - 704 AD - Department of Cell Biology and Signal Transduction, Institut de Genetique et de Biologie Moleculaire et Cellulaire (IGBMC), 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, France. germain@titus.u-strasbg.fr SN - 0031-6997 N2 - Nuclear receptor pharmacology has, to a certain extent, led the way, compared with other receptor systems, in the appreciation that ligands may exert very diverse pharmacology, based on their individual chemical structure and the allosteric changes induced in the receptor/accessory protein complex. This can lead to very selective pharmacological effects, which may not necessarily be predicted from the experience with other agonists/partial agonists/antagonists. If this is the case, then drug discovery may be back to drug-specific pharmacology (where each drug may have an original profile), rather than specific-drug pharmacology (where agents specific for a receptor have a distinct profile). As functional selectivity is indeed a crucial mechanism to be considered when going through the drug discovery development process, then initial screens using reconstituted systems may not show the appropriate pharmacology, simply because the required stoichiometry of corepressors and coactivators may not be present to select the best compounds; therefore, multiple effector systems are necessary to screen for differential activation, and, even then, screening with in vivo pathophysiological models may ultimately be required for the selection process-a massive but necessary task for pharmacologists. Thus, the characterization of nuclear receptors and their associated proteins and the ligands that interact with them will remain a challenge to pharmacologists. KW - nuclear KW - receptor KW - review AU - Germain, P AU - Staels, B AU - Dacquet, C AU - Spedding, M AU - Laudet, V PY - 2006/12// UR - http://dx.doi.org/10.1124/pr.58.4.2 ER -