Epothilone pharmacophore model

One of the last attempt to propose a common pharmacophoric model was made in 2001 by some of us, building a new pseudoreceptor for taxanes and epothilones [114] to account for the amount of new structural and biological information available since the first attempt of the minireceptor work [82], A set of 12 taxanes and epothilones was used as training set on which the model was built. The small... 

Winkler JD, Axelsen PH (1996) A Model for the Taxol (Paclitaxel)/Epothilone Pharmacophore. Bioorg Med Chem Lett 6 2963... 

The pharmacophore resulting from the model (Chart 14) identified two main regions responsible for the activity of epothilones, namely the thiazole ring region) and the C3-C5 portion in agreement with the work of Ojima et al. [51], Besides, the model improves this pharmacophore by accounting for the contribution... 

Fig. 8 Overlap of the three pharmacophores representing the interactions found for paclitaxel in the 1JFF structure (A), epothilone A in the NMR-derived structure (B), and epothilone A in the QSAR model from Botta and co-workers (C), respectively. Blue C7-OH (epothilones) oxetane ring (paclitaxel) red C13 carbon (epothilones) phenyl ring (paclitaxel) yellow Cl carbonyl oxygen (epothilones) Cl carbonyl oxygen (paclitaxel) purple thiazole ring (epothilone) C3 benzamide (paclitaxel). (3-tubulin monomer is represented as a green cartoon and residues involved in hydrogen bonds are in orange (hydrogens are omitted for sake of clarity)...

Manetti F, Forli S, Maccari L, et al. 3D QSAR studies of the interaction between (3-tubulin and microtubule stabilizing antimitotic agents (MSAA). A combined pharmacophore generation and pseudoreceptor modeling approach applied to taxanes and epothilones. II Farmaco 2003 58 357-361... 

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