Chimeric microtubule disruptors.
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.
Leese
Mathew P
MP
Medicinal Chemistry & Sterix Ltd., Department of Pharmacy & Pharmacology, University of Bath, Claverton Down, Bath, BA2 7AY, UK.
Jourdan
Fabrice
F
Kimberley
Meriel R
MR
Cozier
Gyles E
GE
Thiyagarajan
Nethaji
N
Stengel
Chloe
C
Regis-Lydi
Sandra
S
Foster
Paul A
PA
Newman
Simon P
SP
Acharya
K Ravi
KR
Ferrandis
Eric
E
Purohit
Atul
A
Reed
Michael J
MJ
Potter
Barry V L
BV
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D024402:Carbonic Anhydrase II / Q000737:chemistry* / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D051379:Mice; D008819:Mice, Nude; D050257:Tubulin Modulators / Q000737:chemistry* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D008024:Ligands; D050257:Tubulin Modulators; D024402:Carbonic Anhydrase II