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Cell Mol Life Sci. 2010 Apr;67(7):1089-104. doi: 10.1007/s00018-009-0245-6. Epub 2010 Jan 28.

Microtubule targeting agents: from biophysics to proteomics.

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  • 1INSERM UMR 911, Centre de Recherche en Oncologie biologique et en Oncopharmacologie, Facult√© de Pharmacie, Aix-Marseille Universit√©, 27 Boulevard Jean Moulin, 13385, Marseille Cedex 05, France.


This review explores various aspects of the interaction between microtubule targeting agents and tubulin, including binding site, affinity, and drug resistance. Starting with the basics of tubulin polymerization and microtubule targeting agent binding, we then highlight how the three-dimensional structures of drug-tubulin complexes obtained on stabilized tubulin are seeded by precise biological and biophysical data. New avenues opened by thermodynamics analysis, high throughput screening, and proteomics for the molecular pharmacology of these drugs are presented. The amount of data generated by biophysical, proteomic and cellular techniques shed more light onto the microtubule-tubulin equilibrium and tubulin-drug interaction. Combining these approaches provides new insight into the mechanism of action of known microtubule interacting agents and rapid in-depth characterization of next generation molecules targeting the interaction between microtubules and associated modulators of their dynamics. This will facilitate the design of improved and/or alternative chemotherapies targeting the microtubule cytoskeleton.

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