{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["106(43)"],"submitter":["Biggadike K"],"pubmed_abstract":["Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal"],"journal":["Proceedings of the National Academy of Sciences of the United States of America"],"pagination":["18114-9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2775345"],"repository":["biostudies-literature"],"pubmed_title":["Design and x-ray crystal structures of high-potency nonsteroidal glucocorticoid agonists exploiting a novel binding site on the receptor."],"pmcid":["PMC2775345"],"pubmed_authors":["Taylor SJ","Bledsoe RK","Madauss KP","Cooper TW","Coe DM","Iannone MA","Williams SP","McLay IM","House D","Biggadike K","Shipley TJ","Weller V","Macdonald SJ","Uings IJ","Tran TB"],"additional_accession":[]},"is_claimable":false,"name":"Design and x-ray crystal structures of high-potency nonsteroidal glucocorticoid agonists exploiting a novel binding site on the receptor.","description":"Crystallography and computer modeling have been used to exploit a previously unexplored channel in the glucocorticoid receptor (GR). Highly potent, nonsteroidal indazole amides showing excellent complementarity to the channel were designed with the assistance of the computational technique AlleGrow. The accuracy of the design process was demonstrated through crystallographic structural determination of the GR ligand-binding domain-agonist complex of the D-prolinamide derivative 11. The utility of the channel was further exemplified through the design of a potent phenylindazole in which structural motifs, seen to interact with the traditional GR ligand pocket, were abandoned and replaced by interactions within the new channel. Occupation of the channel was confirmed with a second GR crystal","dates":{"release":"2009-01-01T00:00:00Z","publication":"2009 Oct","modification":"2026-05-03T21:07:49.795Z","creation":"2019-03-27T00:26:29Z"},"accession":"S-EPMC2775345","cross_references":{"pubmed":["19822747"],"doi":["10.1073/pnas.0909125106"]}}