Always similar to Epo A: The tubulin-bound conformation of a series of C3- and C15-modified epothilones was found to be similar to the NMR-derived structure of tubulin-bound Epo A, based on NMR spectroscopy and computational modeling. The results obtained for two isomeric quinoline-based Epo B analogues suggest that the aromatic side chain moieties contribute to tubulin binding through van der Waals interactions rather than hydrogen bonding.