The Tubulin‐Bound Conformation of Discodermolide Derived by NMR Studies in Solution Supports a Common Pharmacophore Model for Epothilone and Discodermolide

Bound to have similarities: Although the overall shape of discodermolide bound to tubulin resembles the structure of the free ligand, the precise conformation and orientation of the lactone ring are different. A partially overlapping pharmacophore model supported by protein-mediated interligand NOE signals (see picture) is proposed to explain the similar (but not fully equivalent) biological activity of discodermolide and epothilone A.