476414-52-5Relevant articles and documents
ITZ-1, a Client-Selective Hsp90 Inhibitor, Efficiently Induces Heat Shock Factor 1 Activation
Kimura, Haruhide,Yukitake, Hiroshi,Tajima, Yasukazu,Suzuki, Hirobumi,Chikatsu, Tomoko,Morimoto, Shinji,Funabashi, Yasunori,Omae, Hiroaki,Ito, Takashi,Yoneda, Yukio,Takizawa, Masayuki
supporting information; experimental part, p. 18 - 27 (2010/08/06)
ITZ-1 is a chondroprotective agent that inhibits interleukin-1β-induced matrix metalloproteinase-13 (MMP-13) production and suppresses nitric oxide-induced chondrocyte death. Here we describe its mechanisms of action. Heat shock protein 90 (Hsp90) was identified as a specific ITZ-1-binding protein. Almost all known Hsp90 inhibitors have been reported to bind to the Hsp90 N-terminal ATP-binding site and to simultaneously induce degradation and activation of its multiple client proteins. However, within the Hsp90 client proteins, ITZ-1 strongly induces heat shock factor-1 (HSF1) activation and causes mild Raf-1 degradation, but scarcely induces degradation of a broad range of Hsp90 client proteins by binding to the Hsp90 C terminus. These results may explain ITZ-1's inhibition of MMP-13 production, its cytoprotective effect, and its lower cytotoxicity. These results suggest that ITZ-1 is a client-selective Hsp90 inhibitor.
