title: Fluorine- and rhenium-containing geldanamycin derivatives as leads for the development of molecular probes for imaging Hsp90.
abstract: Heat shock protein 90 (Hsp90) is an ATP-dependent molecular chaperone responsible for protein quality control in cells. Hsp90 has been shown to be overexpressed in many human cancers. This has prompted extensive research on Hsp90 inhibitors as novel anticancer agents and, more recently, the development of molecular probes for imaging Hsp90 expression in vivo. This work describes the development of various fluorine-containing and rhenium-containing geldanamycin derivatives as leads for the development of corresponding (18)F-labeled and (99m)Tc-labeled PET and SPECT probes for molecular imaging of Hsp90 expression. All compounds were evaluated in an in vitro ATPase activity assay using Hsp90 isoform Hsp82p. Fluorobenzoylated geldanamycin derivative 5 displayed comparable inhibitory potency like parent compound geldanamycin.
authors: Department of Oncology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada. wuest@ualberta.ca
authors: Frank
authors: F
authors: Wuest
authors: Vincent
authors: V
authors: Bouvet
authors: BaoChan
authors: B
authors: Mai
authors: Paul
authors: P
authors: LaPointe
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D016227:Benzoquinones / Q000737:chemistry*; D005461:Fluorine / Q000737:chemistry*; D018841:HSP90 Heat-Shock Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047029:Lactams, Macrocyclic / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D057054:Molecular Imaging / Q000379:methods*; D012211:Rhenium / Q000737:chemistry*; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D016227:Benzoquinones; C074510:HSP82 protein, S cerevisiae; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D029701:Saccharomyces cerevisiae Proteins; D005461:Fluorine; D012211:Rhenium; D000251:Adenosine Triphosphatases; C001277:geldanamycin