Recent progress with microtubule stabilizers: new compounds, binding modes and cellular activities

Abstract

Nature has yielded numerous classes of chemically distinct microtubule stabilizers. Several of these, including paclitaxel (Taxol) and docetaxel (Taxotere), are important drugs used in the treatment of cancer. New microtubule stabilizers and novel formulations of these agents continue to provide advances in cancer therapy. In this review we cover recent progress in the chemistry and biology of these diverse microtubule stabilizers focusing on the wide range of organisms that produce these compounds, their mechanisms of inhibiting microtubule-dependent processes, mechanisms of drug resistance, and their interactions with tubulin including their distinct binding sites and modes. A new potential role for microtubule stabilizers in neurodegenerative diseases is reviewed.

Fig. 1

Effects of microtubule stabilizers on the cellular interphase microtubule network of A-10 cells.

Fig. 2

Chemical structures of select plant-derived microtubule stabilizers.

Fig. 3

Chemical structures of select marine-derived microtubule stabilizers.

Fig. 4

Chemical structures of select marine-derived microtubule stabilizers.

Fig. 5

Cellular processes dependent on the interphase microtubule network and shown to be disrupted by microtubule stabilizers

Fig. 6

Microtubule structure and binding sites of microtubule stabilizers

Fig. 7

Microtubules are key components of neurons