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

Sara K. Coulup; Gunda I. Georg

doi:10.1016/j.bmcl.2019.05.042

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

Sara K. Coulup, Gunda I. Georg

Medicinal Chemistry

Research output: Contribution to journal › Review article › peer-review

45 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 language	English (US)
Pages (from-to)	1865-1873
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	29
Issue number	15
DOIs	https://doi.org/10.1016/j.bmcl.2019.05.042
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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access

10.1016/j.bmcl.2019.05.042

OpenUrl availability

Full text

Cite this

@article{70b0e8b928014976bd879b66467fac6b,

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

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",

author = "Coulup, {Sara K.} and Georg, {Gunda I.}",

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: {\textcopyright} 2019 Elsevier Ltd",

year = "2019",

month = aug,

day = "1",

doi = "10.1016/j.bmcl.2019.05.042",

language = "English (US)",

volume = "29",

pages = "1865--1873",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "15",

}

TY - JOUR

T1 - Revisiting microtubule targeting agents

T2 - α-Tubulin and the pironetin binding site as unexplored targets for cancer therapeutics

AU - Coulup, Sara K.

AU - Georg, Gunda I.

N1 - 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

PY - 2019/8/1

Y1 - 2019/8/1

N2 - 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.

AB - 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.

KW - Chemotherapeutics

KW - Microtubule targeting agents

KW - Pironetin

KW - Structural biology

KW - α-Tubulin

UR - http://www.scopus.com/inward/record.url?scp=85065984425&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065984425&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2019.05.042

DO - 10.1016/j.bmcl.2019.05.042

M3 - Review article

C2 - 31130264

AN - SCOPUS:85065984425

SN - 0960-894X

VL - 29

SP - 1865

EP - 1873

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 15

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

Access

OpenUrl availability

Other files and links

Fingerprint

Cite this