A chemical probe for the ATAD2 bromodomain

Paul Bamborough; Chun-wa Chung; Emmanuel H. Demont; Rebecca C. Furze; Andrew J. Bannister; Ka Hing Che; Hawa Diallo; Clement Douault; Paola Grandi; Tony Kouzarides; Anne-Marie Michon; Darren J. Mitchell; Rab K. Prinjha; Christina Rau; Samuel Robson; Robert J. Sheppard; Richard Upton; Robert J. Watson

doi:10.1002/anie.201603928

A chemical probe for the ATAD2 bromodomain

Paul Bamborough
, Chun-wa Chung
, Emmanuel H. Demont
, Rebecca C. Furze
, Andrew J. Bannister
, Ka Hing Che
, Hawa Diallo
, Clement Douault
, Paola Grandi
, Tony Kouzarides
, Anne-Marie Michon
, Darren J. Mitchell
, Rab K. Prinjha
, Christina Rau
, Samuel Robson
, Robert J. Sheppard
, Richard Upton
, Robert J. Watson

Research output: Contribution to journal › Article › peer-review

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Abstract

ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF₂ as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

Original language	English
Pages (from-to)	11382-11386
Number of pages	5
Journal	Angewandte Chemie International Edition
Volume	55
Issue number	38
Early online date	17 Aug 2016
DOIs	https://doi.org/10.1002/anie.201603928
Publication status	Published - 12 Sept 2016
Externally published	Yes

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

RCUK
BBSRC
RG69031

Access to Document

10.1002/anie.201603928

A Chemical Probe
This is the peer reviewed version of the following article: P. Bamborough, C.-w. Chung, E. H. Demont, R. C. Furze, A. J. Bannister, K. H. Che, H. Diallo, C. Douault, P. Grandi, T. Kouzarides, A.-M. Michon, D. J. Mitchell, R. K. Prinjha, C. Rau, S. Robson, R. J. Sheppard, R. Upton, R. J. Watson, Angew. Chem. Int. Ed. 2016, 55, 11382., which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/anie.201603928/full. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.
Accepted author manuscript (Post-print), 544 KB

http://doi.wiley.com/10.1002/anie.201603928

Cite this

Bamborough, P., Chung, C., Demont, E. H., Furze, R. C., Bannister, A. J., Che, K. H., Diallo, H., Douault, C., Grandi, P., Kouzarides, T., Michon, A.-M., Mitchell, D. J., Prinjha, R. K., Rau, C., Robson, S., Sheppard, R. J., Upton, R., & Watson, R. J. (2016). A chemical probe for the ATAD2 bromodomain. Angewandte Chemie International Edition, 55(38), 11382-11386. https://doi.org/10.1002/anie.201603928

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title = "A chemical probe for the ATAD2 bromodomain",

abstract = "ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.",

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month = sep,

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doi = "10.1002/anie.201603928",

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Bamborough, P, Chung, C, Demont, EH, Furze, RC, Bannister, AJ, Che, KH, Diallo, H, Douault, C, Grandi, P, Kouzarides, T, Michon, A-M, Mitchell, DJ, Prinjha, RK, Rau, C, Robson, S, Sheppard, RJ, Upton, R & Watson, RJ 2016, 'A chemical probe for the ATAD2 bromodomain', Angewandte Chemie International Edition, vol. 55, no. 38, pp. 11382-11386. https://doi.org/10.1002/anie.201603928

TY - JOUR

T1 - A chemical probe for the ATAD2 bromodomain

AU - Bamborough, Paul

AU - Chung, Chun-wa

AU - Demont, Emmanuel H.

AU - Furze, Rebecca C.

AU - Bannister, Andrew J.

AU - Che, Ka Hing

AU - Diallo, Hawa

AU - Douault, Clement

AU - Grandi, Paola

AU - Kouzarides, Tony

AU - Michon, Anne-Marie

AU - Mitchell, Darren J.

AU - Prinjha, Rab K.

AU - Rau, Christina

AU - Robson, Samuel

AU - Sheppard, Robert J.

AU - Upton, Richard

AU - Watson, Robert J.

PY - 2016/9/12

Y1 - 2016/9/12

N2 - ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

AB - ATAD2 is a cancer-associated protein whose bromodomain has been described as among the least druggable of that target class. Starting from a potent lead, permeability and selectivity were improved through a dual approach: 1) using CF2 as a sulfone bio-isostere to exploit the unique properties of fluorine, and 2) using 1,3-interactions to control the conformation of a piperidine ring. This resulted in the first reported low-nanomolar, selective and cell permeable chemical probe for ATAD2.

KW - RCUK

KW - BBSRC

KW - RG69031

UR - https://www.repository.cam.ac.uk/

U2 - 10.1002/anie.201603928

DO - 10.1002/anie.201603928

M3 - Article

SN - 1433-7851

VL - 55

SP - 11382

EP - 11386

JO - Angewandte Chemie International Edition

JF - Angewandte Chemie International Edition

IS - 38

ER -

A chemical probe for the ATAD2 bromodomain

Abstract

UN SDGs

Keywords

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