Characterization of a highly selective inhibitor of the Aurora kinases

Fleur M. Ferguson, Zainab M. Doctor, Apirat Chaikuad, Taebo Sim, Nam Doo Kim, Stefan Knapp, Nathanael S. Gray

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound 2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.

Original languageEnglish
Pages (from-to)4405-4408
Number of pages4
JournalBioorganic and Medicinal Chemistry Letters
Volume27
Issue number18
DOIs
Publication statusPublished - 2017 Sep 15

Fingerprint

Aurora Kinases
Aurora Kinase C
Aurora Kinase B
Aurora Kinase A
Mitosis
Cell Cycle
Crystal structure
Cells
X-Rays
Ligands
X rays
Neoplasms

Keywords

  • Aurora kinase
  • Cancer
  • Mitosis
  • Pan-Aurora inhibitor
  • Selective kinase inhibitor

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Ferguson, F. M., Doctor, Z. M., Chaikuad, A., Sim, T., Kim, N. D., Knapp, S., & Gray, N. S. (2017). Characterization of a highly selective inhibitor of the Aurora kinases. Bioorganic and Medicinal Chemistry Letters, 27(18), 4405-4408. https://doi.org/10.1016/j.bmcl.2017.08.016

Characterization of a highly selective inhibitor of the Aurora kinases. / Ferguson, Fleur M.; Doctor, Zainab M.; Chaikuad, Apirat; Sim, Taebo; Kim, Nam Doo; Knapp, Stefan; Gray, Nathanael S.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 27, No. 18, 15.09.2017, p. 4405-4408.

Research output: Contribution to journalArticle

Ferguson, FM, Doctor, ZM, Chaikuad, A, Sim, T, Kim, ND, Knapp, S & Gray, NS 2017, 'Characterization of a highly selective inhibitor of the Aurora kinases', Bioorganic and Medicinal Chemistry Letters, vol. 27, no. 18, pp. 4405-4408. https://doi.org/10.1016/j.bmcl.2017.08.016
Ferguson, Fleur M. ; Doctor, Zainab M. ; Chaikuad, Apirat ; Sim, Taebo ; Kim, Nam Doo ; Knapp, Stefan ; Gray, Nathanael S. / Characterization of a highly selective inhibitor of the Aurora kinases. In: Bioorganic and Medicinal Chemistry Letters. 2017 ; Vol. 27, No. 18. pp. 4405-4408.
@article{43375fe145104e4c895e132e75e4804a,
title = "Characterization of a highly selective inhibitor of the Aurora kinases",
abstract = "Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound 2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.",
keywords = "Aurora kinase, Cancer, Mitosis, Pan-Aurora inhibitor, Selective kinase inhibitor",
author = "Ferguson, {Fleur M.} and Doctor, {Zainab M.} and Apirat Chaikuad and Taebo Sim and Kim, {Nam Doo} and Stefan Knapp and Gray, {Nathanael S.}",
year = "2017",
month = "9",
day = "15",
doi = "10.1016/j.bmcl.2017.08.016",
language = "English",
volume = "27",
pages = "4405--4408",
journal = "Bioorganic and Medicinal Chemistry Letters",
issn = "0960-894X",
publisher = "Elsevier Limited",
number = "18",

}

TY - JOUR

T1 - Characterization of a highly selective inhibitor of the Aurora kinases

AU - Ferguson, Fleur M.

AU - Doctor, Zainab M.

AU - Chaikuad, Apirat

AU - Sim, Taebo

AU - Kim, Nam Doo

AU - Knapp, Stefan

AU - Gray, Nathanael S.

PY - 2017/9/15

Y1 - 2017/9/15

N2 - Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound 2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.

AB - Aurora kinases play an essential role in mitosis and cell cycle regulation. In recent years Aurora kinases have proved popular cancer targets and many inhibitors have been developed. The majority of these clinical candidates are multi-targeted, rendering them inappropriate as tools for studying Aurora kinase mediated signaling. Here we report discovery of a highly selective inhibitor of Aurora kinases A, B and C, with potent cellular activity and minimal off-target activity (PLK4). The X-ray co-crystal structure of Aurora A in complex with compound 2 is reported, and provides insights into the structural determinants of ligand binding and selectivity.

KW - Aurora kinase

KW - Cancer

KW - Mitosis

KW - Pan-Aurora inhibitor

KW - Selective kinase inhibitor

UR - http://www.scopus.com/inward/record.url?scp=85028763688&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85028763688&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2017.08.016

DO - 10.1016/j.bmcl.2017.08.016

M3 - Article

C2 - 28818446

AN - SCOPUS:85028763688

VL - 27

SP - 4405

EP - 4408

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

SN - 0960-894X

IS - 18

ER -