ChemMedChem

Cover image for Vol. 12 Issue 10

Editorial Board Chairs: Antonello Mai, Rainer Metternich. Assoc. Editors: David Peralta, Scott Williams (Sr)

Impact Factor: 2.98

ISI Journal Citation Reports © Ranking: 2015: 18/59 (Chemistry Medicinal); 77/255 (Pharmacology & Pharmacy)

Online ISSN: 1860-7187

Associated Title(s): Angewandte Chemie International Edition, Chemistry - A European Journal, Chemistry – An Asian Journal, ChemBioChem, Medicinal Research Reviews, Molecular Informatics

November 13, 2009

VIP: Evaluation of Novel Epothilone Analogues by means of a Common Pharmacophore and a QSAR Pseudoreceptor Model for Taxanes and Epothilones

VIP: Evaluation of Novel Epothilone Analogues by means of a Common Pharmacophore and a QSAR Pseudoreceptor Model for Taxanes and Epothilones

Stefano Forli, Fabrizio Manetti, Karl-Heinz Altmann*, Maurizio Botta*

The epothilones and taxanes are the two most important classes of microtubule-stabilizing antimitotic agents in clinical use for the treatment of cancer. Both compound types elicit their antitumor effects by binding specifically to β-tubulin, the protein building block of cellular microtubules. Just how these compounds interact with β-tubulin, however, is still a matter of debate.

Despite significant differences in structure, it was initially thought that both taxanes and epothilones interact with β-tubulin through a common pharmacophore. This hypothesis was later challenged by electron crystallographic studies, but then additional support for the common pharmacophore hypothesis came from results of NMR structural work.

To help resolve this issue of how epothilones and taxanes bind their common target, Botta, Altmann, and co-workers applied a 3D QSAR pseudoreceptor model toward a series of recently reported epothilone derivatives. Their findings, backed up by experimental work, support a return to the initial hypothesis of a common pharmacophore in β-tubulin binding for both epothilones and taxanes.

Received July 22, 2009; published online November 10, 2009, DOI: 10.1002/cmdc.200900303.

Your Comment...

[Browse more news]

SEARCH

SEARCH BY CITATION