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 language | English (US) |
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Pages (from-to) | 1865-1873 |
Number of pages | 9 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 29 |
Issue number | 15 |
DOIs | |
State | Published - 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
Keywords
- Chemotherapeutics
- Microtubule targeting agents
- Pironetin
- Structural biology
- α-Tubulin