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. 2010 May 7;46(17):2907-9.
doi: 10.1039/c002558e. Epub 2010 Mar 20.

Chimeric microtubule disruptors

Mathew P Leese  1 , Fabrice Jourdan, Meriel R Kimberley, Gyles E Cozier, Nethaji Thiyagarajan, Chloe Stengel, Sandra Regis-Lydi, Paul A Foster, Simon P Newman, K Ravi Acharya, Eric Ferrandis, Atul Purohit, Michael J Reed, Barry V L Potter
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Chimeric microtubule disruptors

Mathew P Leese et al. Chem Commun (Camb). .

Abstract

A chimeric approach is used to discover microtubule disruptors with excellent in vitro activity and oral bioavailability; a ligand-protein interaction with carbonic anhydrase that enhances bioavailability is characterised by protein X-ray crystallography. Dosing of a representative chimera in a tumour xenograft model confirms the excellent therapeutic potential of the class.

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