Revisiting microtubule targeting agents: α-Tubulin and the pironetin binding site as unexplored targets for cancer therapeutics

Bioorg Med Chem Lett. 2019 Aug 1;29(15):1865-1873. doi: 10.1016/j.bmcl.2019.05.042.

Sara K Coulup ¹, Gunda I Georg ²

Affiliations

1 Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware St SE, Minneapolis, MN 55414, USA.
2 Department of Medicinal Chemistry and Institute for Therapeutics Discovery and Development, University of Minnesota, 717 Delaware St SE, Minneapolis, MN 55414, USA. Electronic address: georg@umn.edu.

PMID: 31130264 DOI: 10.1016/j.bmcl.2019.05.042

Abstract

Molecules that bind to tubulin and disrupt tubulin dynamics are known as microtubule targeting agents. Treatment with a microtubule targeting agent leads to cell cycle arrest followed by Apoptosis. Tubulin inhibitors have been highly effective in the clinical treatment of a variety of tumors and are being investigated for treatment of several Other Diseases. Currently, all FDA approved microtubule inhibitors bind to β-tubulin. Given the overall success of tubulin-binding agents in Anticancer chemotherapy, α-tubulin is an attractive and unexplored target. Herein, we will discuss pironetin, the only compound known to bind α-tubulin, with particular focus on the known biological properties, the total syntheses, exploration of its structure-activity relationship, and future directions.

Keywords

Chemotherapeutics; Microtubule targeting agents; Pironetin; Structural biology; α-Tubulin.

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