title: Molecular characterization of macbecin as an Hsp90 inhibitor.
abstract: Macbecin compares favorably to geldanamycin as an Hsp90 inhibitor, being more soluble, stable, more potently inhibiting ATPase activity (IC50 = 2 microM) and binding with higher affinity (Kd = 0.24 microM). 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.
authors: Biotica Technology Limited, Chesterford Research Park, Essex CB10 1XL, U.K. christine.martin@biotica.com
authors: Christine J
authors: CJ
authors: Martin
authors: Sabine
authors: S
authors: Gaisser
authors: Iain R
authors: IR
authors: Challis
authors: Isabelle
authors: I
authors: Carletti
authors: Barrie
authors: B
authors: Wilkinson
authors: Matthew
authors: M
authors: Gregory
authors: Chrisostomos
authors: C
authors: Prodromou
authors: S Mark
authors: SM
authors: Roe
authors: Laurence H
authors: LH
authors: Pearl
authors: Susan M
authors: SM
authors: Boyd
authors: Ming-Qiang
authors: MQ
authors: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D016227:Benzoquinones / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D006801:Humans; D047029:Lactams, Macrocyclic / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding; D013816:Thermodynamics; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; D016227:Benzoquinones; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; C025514:macbecin I