title: 6-Alkylsalicylic acid analogues inhibit in vitro ATPase activity of heat shock protein 90.
abstract: The molecular chaperone heat shock protein 90 (Hsp90) is responsible for maintaining the correct folding and stability of many signaling proteins. It is a promising target of cancer therapeutics and several other diseases, including neurodegenerative disease, nerve injuries, inflammation, and infection. In an effort to identify new Hsp90 inhibitors from natural sources using an in vitro ATPase inhibition assay, two 6-alkylsalicylic acid analogues, salaceyin A and B were identified from the culture extract of Streptomyces. Salaceyin A and B exhibited moderate ATPase inhibitory activities with IC(50) values of 68.3 and 65.2 μM, respectively. Binding of salaceyins to human Hsp90α was examined by competition binding experiments with ATP-Sepharose beads. However, the compounds exhibited no degradation activity of Hsp90 client proteins, Her2, c-Raf, or Akt.
authors.affiliation: KRIBB, Ochang 363-883, Korea.
authors.forename: Cheng-Zhu
authors.initials: CZ
authors.lastname: Wu
authors.forename: An Na
authors.initials: AN
authors.lastname: Moon
authors.forename: Oksik
authors.initials: O
authors.lastname: Choi
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Kang
authors.forename: Jung Joon
authors.initials: JJ
authors.lastname: Lee
authors.forename: Dongho
authors.initials: D
authors.lastname: Lee
authors.forename: Bang Yeon
authors.initials: BY
authors.lastname: Hwang
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Hong-Sub
authors.initials: HS
authors.lastname: Lee
authors.forename: Young-Soo
authors.initials: YS
authors.lastname: Hong
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D001667:Binding, Competitive; D045744:Cell Line, Tumor; D005260:Female; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018832:Molecular Chaperones / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D012459:Salicylates / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D012685:Sepharose / Q000031:analogs & derivatives / Q000378:metabolism; D013302:Streptomyces / Q000737:chemistry
chemical_list: D000251:Adenosine Triphosphatases; D000255:Adenosine Triphosphate; D000970:Antineoplastic Agents; D018841:HSP90 Heat-Shock Proteins; D018832:Molecular Chaperones; D051057:Proto-Oncogene Proteins c-akt; D019908:Proto-Oncogene Proteins c-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D012459:Salicylates; D012685:Sepharose; C030548:ATP-sepharose; C518209:salaceyin A; C518210:salaceyin B; C508053:ERBB2 protein, human