The discovery and development of Eg5 inhibitors for the clinic

James A. D. Good, Giacomo Berretta, Nahoum G. Anthony, Simon P. Mackay

Research output: Chapter in Book/Report/Conference proceedingChapter

2 Citations (Scopus)

Abstract

The mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP, Kif11, a member of the kinesin-5 family) represents an attractive oncology drug target in the ongoing development of anti-mitotic drugs that selectively block mitosis through disruption to the mitotic spindle. In this state-of-the-art review, we outline the progress that has been made in the development of Eg5 inhibitors for clinical use. We evaluate the preclinical development and attributes of key Eg5 inhibitors that have undergone clinical evaluation or extensive preclinical optimisation, and discuss the medicinal chemistry strategies utilised in their design to overcome the challenges encountered during lead optimisation. We critically analyse the progress that has been made towards delivering clinical benefits, and the wider implications this has in the utility of mitotic kinesin inhibitors as prospective oncology drugs.

LanguageEnglish
Title of host publicationKinesins and Cancer
EditorsFrank Kozielski
PublisherSense Publishers
Pages27-52
Number of pages26
ISBN (Print)978-94-017-9731-3
DOIs
Publication statusPublished - 1 Jan 2015

Fingerprint

Kinesin
Oncology
Pharmaceutical Preparations
Spindle Apparatus
Pharmaceutical Chemistry
Mitosis
Proteins

Keywords

  • anti-mitotic
  • drug discovery
  • Eg5
  • kinesins
  • multiple myeloma

Cite this

Good, J. A. D., Berretta, G., Anthony, N. G., & Mackay, S. P. (2015). The discovery and development of Eg5 inhibitors for the clinic. In F. Kozielski (Ed.), Kinesins and Cancer (pp. 27-52). Sense Publishers. https://doi.org/10.1007/978-94-017-9732-0_2
Good, James A. D. ; Berretta, Giacomo ; Anthony, Nahoum G. ; Mackay, Simon P. / The discovery and development of Eg5 inhibitors for the clinic. Kinesins and Cancer. editor / Frank Kozielski. Sense Publishers, 2015. pp. 27-52
@inbook{03b208df6d834e6984f26f63b765f37d,
title = "The discovery and development of Eg5 inhibitors for the clinic",
abstract = "The mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP, Kif11, a member of the kinesin-5 family) represents an attractive oncology drug target in the ongoing development of anti-mitotic drugs that selectively block mitosis through disruption to the mitotic spindle. In this state-of-the-art review, we outline the progress that has been made in the development of Eg5 inhibitors for clinical use. We evaluate the preclinical development and attributes of key Eg5 inhibitors that have undergone clinical evaluation or extensive preclinical optimisation, and discuss the medicinal chemistry strategies utilised in their design to overcome the challenges encountered during lead optimisation. We critically analyse the progress that has been made towards delivering clinical benefits, and the wider implications this has in the utility of mitotic kinesin inhibitors as prospective oncology drugs.",
keywords = "anti-mitotic, drug discovery, Eg5, kinesins, multiple myeloma",
author = "Good, {James A. D.} and Giacomo Berretta and Anthony, {Nahoum G.} and Mackay, {Simon P.}",
year = "2015",
month = "1",
day = "1",
doi = "10.1007/978-94-017-9732-0_2",
language = "English",
isbn = "978-94-017-9731-3",
pages = "27--52",
editor = "Frank Kozielski",
booktitle = "Kinesins and Cancer",
publisher = "Sense Publishers",
address = "Netherlands",

}

Good, JAD, Berretta, G, Anthony, NG & Mackay, SP 2015, The discovery and development of Eg5 inhibitors for the clinic. in F Kozielski (ed.), Kinesins and Cancer. Sense Publishers, pp. 27-52. https://doi.org/10.1007/978-94-017-9732-0_2

The discovery and development of Eg5 inhibitors for the clinic. / Good, James A. D.; Berretta, Giacomo; Anthony, Nahoum G.; Mackay, Simon P.

Kinesins and Cancer. ed. / Frank Kozielski. Sense Publishers, 2015. p. 27-52.

Research output: Chapter in Book/Report/Conference proceedingChapter

TY - CHAP

T1 - The discovery and development of Eg5 inhibitors for the clinic

AU - Good, James A. D.

AU - Berretta, Giacomo

AU - Anthony, Nahoum G.

AU - Mackay, Simon P.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - The mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP, Kif11, a member of the kinesin-5 family) represents an attractive oncology drug target in the ongoing development of anti-mitotic drugs that selectively block mitosis through disruption to the mitotic spindle. In this state-of-the-art review, we outline the progress that has been made in the development of Eg5 inhibitors for clinical use. We evaluate the preclinical development and attributes of key Eg5 inhibitors that have undergone clinical evaluation or extensive preclinical optimisation, and discuss the medicinal chemistry strategies utilised in their design to overcome the challenges encountered during lead optimisation. We critically analyse the progress that has been made towards delivering clinical benefits, and the wider implications this has in the utility of mitotic kinesin inhibitors as prospective oncology drugs.

AB - The mitotic kinesin Eg5 (also known as kinesin spindle protein, KSP, Kif11, a member of the kinesin-5 family) represents an attractive oncology drug target in the ongoing development of anti-mitotic drugs that selectively block mitosis through disruption to the mitotic spindle. In this state-of-the-art review, we outline the progress that has been made in the development of Eg5 inhibitors for clinical use. We evaluate the preclinical development and attributes of key Eg5 inhibitors that have undergone clinical evaluation or extensive preclinical optimisation, and discuss the medicinal chemistry strategies utilised in their design to overcome the challenges encountered during lead optimisation. We critically analyse the progress that has been made towards delivering clinical benefits, and the wider implications this has in the utility of mitotic kinesin inhibitors as prospective oncology drugs.

KW - anti-mitotic

KW - drug discovery

KW - Eg5

KW - kinesins

KW - multiple myeloma

UR - http://www.scopus.com/inward/record.url?scp=84943196508&partnerID=8YFLogxK

U2 - 10.1007/978-94-017-9732-0_2

DO - 10.1007/978-94-017-9732-0_2

M3 - Chapter

SN - 978-94-017-9731-3

SP - 27

EP - 52

BT - Kinesins and Cancer

A2 - Kozielski, Frank

PB - Sense Publishers

ER -

Good JAD, Berretta G, Anthony NG, Mackay SP. The discovery and development of Eg5 inhibitors for the clinic. In Kozielski F, editor, Kinesins and Cancer. Sense Publishers. 2015. p. 27-52 https://doi.org/10.1007/978-94-017-9732-0_2