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Molecular characterization of macbecin as an Hsp90 inhibitor
journal contribution
posted on 2023-06-08, 06:58 authored by Christine J Martin, Sabine Gaisser, Iain R Challis, Isabelle Carletti, Barrie Wilkinson, Matthew Gregory, Chrisostomos ProdromouChrisostomos Prodromou, S Mark Roe, Laurence PearlLaurence Pearl, Susan M Boyd, Ming-Qiang ZhangMacbecin compares favorably to geldanamycin as an Hsp90 inhibitor, being more soluble, stable, more potently inhibiting ATPase activity (IC50 = 2 mu M) and binding with higher affinity (K-d = 0.24 mu M). 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 TIC: 32%) in a DU145 murine xenograft. Macbecin thus represents an attractive lead for further optimization.
History
Publication status
- Published
Journal
Journal of Medicinal ChemistryISSN
0022-2623Publisher
American Chemical SocietyExternal DOI
Issue
9Volume
51Page range
2853-2857Department affiliated with
- Biochemistry Publications
Full text available
- No
Peer reviewed?
- Yes