Chimeric microtubule disruptors.
Leese MP., Jourdan F., Kimberley MR., Cozier GE., Thiyagarajan N., Stengel C., Regis-Lydi S., Foster PA., Newman SP., Acharya KR., Ferrandis E., Purohit A., Reed MJ., Potter BVL.
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.