Lead Identification of β-lactam and Related Imine inhibitors of the Molecular Caperone Heat shock Protein 90

Authors

Niamh O'Boyle, Technological University DublinFollow
Andrew JS Knox, Trinity College Dublin, IrelandFollow
Trevor P. Price, Trinity College Dublin Ireland
D. Clive Williams, Trinity College Dublin, Ireland
Daniela M. Zisterer, Trinity College Dublin IrelandFollow
David G. Lloyd, Trinity College Dublin, Ireland
Mary J. Meegan, Trinity College Dublin IrelandFollow

Document Type

Article

Rights

This item is available under a Creative Commons License for non-commercial use only

Disciplines

1. NATURAL SCIENCES, 1.4 CHEMICAL SCIENCES, Organic Chemistry, 1.6 BIOLOGICAL SCIENCES, Biochemistry and molecular biology

Publication Details

Bioorganic and Medicinal Chemistry, 2011, Vol. 19, Pages 6055 – 6068

doi: http://dx.doi.org/10.1016/j.bmc.2011.08.048

Abstract

Heat shock protein 90 is an emerging target for oncology therapeutics. Inhibitors of this molecular chaperone, which is responsible for the maintenance of a number of oncogenic proteins, have shown promise in clinical trials and represent a new and exciting area in the treatment of cancer. Heat shock protein 90 inhibitors have huge structural diversity, and here we present the identification of inhibitors based on β-lactam and imine templates. β-Lactam 5 and imines 12 and 18 exhibit binding to heat shock protein 90-α with IC₅₀ values of 5.6 μM, 14.5 μM and 22.1 μM respectively. The binding affinity displayed by these compounds positions them as lead compounds for the design of future inhibitors of heat shock protein 90 based on the β-lactam and imine templates.

DOI

https://doi.org/10.1016/j.bmc.2011.08.048

Recommended Citation

O'Boyle, N. et al (2011). Lead identification of β-lactam and related imine inhibitors of the molecular chaperone heat shock protein 90. Bioorganic and Medicinal Chemistry19, pp, 6055 – 6068. doi:http://dx.doi.org/10.1016/j.bmc.2011.08.048