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Review
. 2017 Aug 9;18(8):1733.
doi: 10.3390/ijms18081733.

Taxol®: The First Microtubule Stabilizing Agent

Chia-Ping Huang Yang  1   2 , Susan Band Horwitz  3
Affiliations
Review

Taxol®: The First Microtubule Stabilizing Agent

Chia-Ping Huang Yang et al. Int J Mol Sci. .

Abstract

Taxol®, an antitumor drug with significant activity, is the first microtubule stabilizing agent described in the literature. This short review of the mechanism of action of Taxol® emphasizes the research done in the Horwitz' laboratory. It discusses the contribution of photoaffinity labeled analogues of Taxol® toward our understanding of the binding site of the drug on the microtubule. The importance of hydrogen/deuterium exchange experiments to further our insights into the stabilization of microtubules by Taxol® is addressed. The development of drug resistance, a major problem that arises in the clinic, is discussed. Studies describing differential drug binding to distinct β-tubulin isotypes are presented. Looking forward, it is suggested that the β-tubulin isotype content of a tumor may influence its responses to Taxol®.

Keywords: Taxol®; drug binding site; drug resistance; photoaffinity labeling; tubulin isotypes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Structure of Taxol®.
Figure 2
Figure 2
Photolabeling sites on β-tubulin obtained with three photoaffinity analogues of Taxol®. Asterisks represent [3H].
Figure 3
Figure 3
Sequence alignment of the leucine cluster of human β-tubulin isotypes. The asterisk denotes an altered residue (in red).
Figure 4
Figure 4
βIII-tubulin subunit contains a unique residue 218 (T218A) in the leucine cluster. (A) β-tubulin subunit (grey) in complex with Taxol® (stick representation) and GDP (green). Four C-α (CA) atoms (red spheres) are used to define the binding pocket dimensions. T218 has negligible interactions with Taxol®; (B) Data from molecular dynamics simulations are shown. Figure adapted from Yang et al. [57].
See this image and copyright information in PMC

References

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