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

Sara K. Coulup, Gunda I. Georg

Research output: Contribution to journalReview articlepeer-review

5 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1865-1873
Number of pages9
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number15
DOIs
StatePublished - Aug 1 2019

Bibliographical note

Funding Information:
S. K. C. was supported by a NIH training grant from the National Institute of General Medical Sciences USA (5 T32 GM008700 ) and a NIH Ruth L. Kirschstein National Research Service Award from the National Cancer Institute USA (NIH/NCI 5F31CA203039). The authors would like to thank Peter Ycas, Erick Carlson, and Dr. C. Leigh Allen for many helpful discussions.

Funding Information:
S. K. C. was supported by a NIH training grant from the National Institute of General Medical Sciences USA (5T32 GM008700) and a NIH Ruth L. Kirschstein National Research Service Award from the National Cancer Institute USA (NIH/NCI 5F31CA203039). The authors would like to thank Peter Ycas, Erick Carlson, and Dr. C. Leigh Allen for many helpful discussions.

Publisher Copyright:
© 2019 Elsevier Ltd

Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.

Keywords

  • Chemotherapeutics
  • Microtubule targeting agents
  • Pironetin
  • Structural biology
  • α-Tubulin

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