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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Antineoplastic Agents / chemical synthesis
-
Antineoplastic Agents / chemistry*
-
Antineoplastic Agents / pharmacology
-
Binding Sites
-
Carbonic Anhydrase II / chemistry*
-
Carbonic Anhydrase II / metabolism
-
Carbonic Anhydrase Inhibitors / chemical synthesis
-
Carbonic Anhydrase Inhibitors / chemistry
-
Carbonic Anhydrase Inhibitors / pharmacology
-
Cell Line, Tumor
-
Computer Simulation
-
Crystallography, X-Ray
-
Humans
-
Ligands
-
Mice
-
Mice, Nude
-
Tubulin Modulators / chemistry*
-
Tubulin Modulators / metabolism
-
Xenograft Model Antitumor Assays
Substances
-
Antineoplastic Agents
-
Carbonic Anhydrase Inhibitors
-
Ligands
-
Tubulin Modulators
-
Carbonic Anhydrase II