title: C-terminal heat shock protein 90 modulators produce desirable oncogenic properties.
abstract: The cellular protection mechanism, the heat shock response, is only activated by classical heat shock 90 inhibitors (Hsp90) that "target" the N-terminus of the protein, but not by those that modulate the C-terminus. Significant differences in cytotoxicity (nanomolar) for classical inhibitors versus their ability to modulate Hsp90 (low micromolar) are discussed. In contrast, molecules that modulate Hsp90's C-terminus show similar IC50 values for cytotoxicity and Hsp90 inhibition. A comparison between the two types of Hsp90 inhibitors suggests that classical inhibitors may be modulating an alternative biological target that stresses the cell rather directly inhibiting Hsp90, whereas C-terminal modulators are most likely acting by directly inhibiting Hsp90.
authors.affiliation: Department of Chemistry, The University of New South Wales, Gate 2 High street, Sydney, NSW 2052, Australia. s.mcalpine@unsw.edu.au.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: S R
authors.initials: SR
authors.lastname: McAlpine
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017209:Apoptosis; D045744:Cell Line, Tumor; D015195:Drug Design; D045325:HCT116 Cells; D018841:HSP90 Heat-Shock Proteins / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000378:metabolism; D010641:Phenotype; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000737:chemistry; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D012333:RNA, Messenger