Molecular Characterization of Macbecin as an Hsp90 Inhibitor

详细信息    查看全文

• 作者：Christine J. Martin ; Sabine Gaisser ; Iain R. Challis ; Isabelle Carletti ; Barrie Wilkinson ; Matthew Gregory ; Chrisostomos Prodromou ; S. Mark Roe ; Laurence H. Pearl ; Susan M. Boyd ; Ming-Qiang Zhang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2008
• 出版时间：May 8, 2008
• 年：2008
• 卷：51
• 期：9
• 页码：2853 - 2857
• 全文大小：574K
• 年卷期：v.51,no.9(May 8, 2008)
• ISSN：1520-4804

文摘

Macbecin compares favorably to geldanamycin as an Hsp90 inhibitor, being more soluble, stable, more potently inhibiting ATPase activity (IC₅₀ = 2 µM) and binding with higher affinity (K_d = 0.24 µM). Structural studies reveal significant differences in their Hsp90 binding characteristics, and macbecin-induced tumor cell growth inhibition is accompanied by characteristic degradation of Hsp90 client proteins. Macbecin significantly reduced tumor growth rates (minimum T/C: 32%) in a DU145 murine xenograft. Macbecin thus represents an attractive lead for further optimization.