{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Barrott JJ"],"funding":["NIAID NIH HHS"],"pagination":["1187-97"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC3815696"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["20(9)"],"pubmed_abstract":["Inhibitors of heat-shock protein 90 (Hsp90) have demonstrated an unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained, but could be influenced by ectopically expressed Hsp90 in tumors. In this work, we synthesized Hsp90 inhibitors that can carry optical or radioiodinated probes via a polyethyleneglycol tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein occurs at the plasma membrane. In mice, we observed exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showe"],"journal":["Chemistry & biology"],"pubmed_title":["Optical and radioiodinated tethered Hsp90 inhibitors reveal selective internalization of ectopic Hsp90 in malignant breast tumor cells."],"pmcid":["PMC3815696"],"funding_grant_id":["1R01AI090644-01","R01 AI089526","1R01-AI089526-01","R01 AI090644"],"pubmed_authors":["Spector NL","Osada T","Zalutsky MR","Neckers L","Rajaram N","Yang XY","Haystead TA","Hu F","Hartman ZC","Loiselle DR","Ramanujam N","Lyerly HK","Barrott JJ","Hughes PF","Vaidyanathan G"],"additional_accession":[]},"is_claimable":false,"name":"Optical and radioiodinated tethered Hsp90 inhibitors reveal selective internalization of ectopic Hsp90 in malignant breast tumor cells.","description":"Inhibitors of heat-shock protein 90 (Hsp90) have demonstrated an unusual selectivity for tumor cells despite its ubiquitous expression. This phenomenon has remained unexplained, but could be influenced by ectopically expressed Hsp90 in tumors. In this work, we synthesized Hsp90 inhibitors that can carry optical or radioiodinated probes via a polyethyleneglycol tether. We show that these tethered inhibitors selectively recognize cells expressing ectopic Hsp90 and become internalized. The internalization process is blocked by Hsp90 antibodies, suggesting that active cycling of the protein occurs at the plasma membrane. In mice, we observed exquisite accumulation of the fluor-tethered versions within breast tumors at very sensitive levels. Cell-based assays with the radiolabeled version showe","dates":{"release":"2013-01-01T00:00:00Z","publication":"2013 Sep","modification":"2025-04-18T14:08:08.06Z","creation":"2019-03-27T01:17:59Z"},"accession":"S-EPMC3815696","cross_references":{"pubmed":["24035283"],"doi":["10.1016/j.chembiol.2013.08.004"]}}