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A fluorescence polarization assay for inhibitors of Hsp90

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A fluorescence polarization assay for inhibitors of Hsp90. / Howes, R.; Barril, Xavier; Dymock, Brian; Grant, Katherine; Northfield, C. J.; Robertson, A. G. S.; Surgenor, Allan; Wayne, J.; Wright, Lisa; Ball, Karen; Matthews, Thomas P.; Cheung, K.-M.; MacDonald, E.; Workman, Paul; Drysdale, Martin J.

In: Analytical Biochemistry, Vol. 350, No. 2, 15.03.2006, p. 202-213.

Research output: Contribution to journalArticlepeer-review

Harvard

Howes, R, Barril, X, Dymock, B, Grant, K, Northfield, CJ, Robertson, AGS, Surgenor, A, Wayne, J, Wright, L, Ball, K, Matthews, TP, Cheung, K-M, MacDonald, E, Workman, P & Drysdale, MJ 2006, 'A fluorescence polarization assay for inhibitors of Hsp90', Analytical Biochemistry, vol. 350, no. 2, pp. 202-213. https://doi.org/10.1016/j.ab.2005.12.023

APA

Howes, R., Barril, X., Dymock, B., Grant, K., Northfield, C. J., Robertson, A. G. S., Surgenor, A., Wayne, J., Wright, L., Ball, K., Matthews, T. P., Cheung, K-M., MacDonald, E., Workman, P., & Drysdale, M. J. (2006). A fluorescence polarization assay for inhibitors of Hsp90. Analytical Biochemistry, 350(2), 202-213. https://doi.org/10.1016/j.ab.2005.12.023

Vancouver

Howes R, Barril X, Dymock B, Grant K, Northfield CJ, Robertson AGS et al. A fluorescence polarization assay for inhibitors of Hsp90. Analytical Biochemistry. 2006 Mar 15;350(2):202-213. https://doi.org/10.1016/j.ab.2005.12.023

Author

Howes, R. ; Barril, Xavier ; Dymock, Brian ; Grant, Katherine ; Northfield, C. J. ; Robertson, A. G. S. ; Surgenor, Allan ; Wayne, J. ; Wright, Lisa ; Ball, Karen ; Matthews, Thomas P. ; Cheung, K.-M. ; MacDonald, E. ; Workman, Paul ; Drysdale, Martin J. / A fluorescence polarization assay for inhibitors of Hsp90. In: Analytical Biochemistry. 2006 ; Vol. 350, No. 2. pp. 202-213.

Bibtex

@article{cf5d6a7dd34a43019d75ba5f46c5bfd3,
title = "A fluorescence polarization assay for inhibitors of Hsp90",
abstract = "Hsp90 encodes a ubiquitous molecular chaperone protein conserved among species which acts on multiple substrates, many of which are important cell-signaling proteins. Inhibition of Hsp90 function has been promoted as a mechanism to degrade client proteins involved in tumorigenesis and disease progression. Several assays to monitor inhibition of Hsp90 function currently exist but are limited in their use for a drug discovery campaign. Using data from the crystal structure of an initial hit compound, we have developed a Xuorescence polarization assay to monitor binding of compounds to the ATP-binding site of Hsp90. This assay is very robust (Z' > 0.9) and can detect aYnity of compounds with IC50s to 40 nM. We have used this assay in conjunction with cocrystal structures of small molecules to drive a structure-based design program aimed at the discovery and optimization of a novel class of potent Hsp90 inhibitors.",
author = "R. Howes and Xavier Barril and Brian Dymock and Katherine Grant and Northfield, {C. J.} and Robertson, {A. G. S.} and Allan Surgenor and J. Wayne and Lisa Wright and Karen Ball and Matthews, {Thomas P.} and K.-M. Cheung and E. MacDonald and Paul Workman and Drysdale, {Martin J.}",
year = "2006",
month = mar,
day = "15",
doi = "10.1016/j.ab.2005.12.023",
language = "English",
volume = "350",
pages = "202--213",
journal = "Analytical Biochemistry",
issn = "0003-2697",
publisher = "Academic Press Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - A fluorescence polarization assay for inhibitors of Hsp90

AU - Howes, R.

AU - Barril, Xavier

AU - Dymock, Brian

AU - Grant, Katherine

AU - Northfield, C. J.

AU - Robertson, A. G. S.

AU - Surgenor, Allan

AU - Wayne, J.

AU - Wright, Lisa

AU - Ball, Karen

AU - Matthews, Thomas P.

AU - Cheung, K.-M.

AU - MacDonald, E.

AU - Workman, Paul

AU - Drysdale, Martin J.

PY - 2006/3/15

Y1 - 2006/3/15

N2 - Hsp90 encodes a ubiquitous molecular chaperone protein conserved among species which acts on multiple substrates, many of which are important cell-signaling proteins. Inhibition of Hsp90 function has been promoted as a mechanism to degrade client proteins involved in tumorigenesis and disease progression. Several assays to monitor inhibition of Hsp90 function currently exist but are limited in their use for a drug discovery campaign. Using data from the crystal structure of an initial hit compound, we have developed a Xuorescence polarization assay to monitor binding of compounds to the ATP-binding site of Hsp90. This assay is very robust (Z' > 0.9) and can detect aYnity of compounds with IC50s to 40 nM. We have used this assay in conjunction with cocrystal structures of small molecules to drive a structure-based design program aimed at the discovery and optimization of a novel class of potent Hsp90 inhibitors.

AB - Hsp90 encodes a ubiquitous molecular chaperone protein conserved among species which acts on multiple substrates, many of which are important cell-signaling proteins. Inhibition of Hsp90 function has been promoted as a mechanism to degrade client proteins involved in tumorigenesis and disease progression. Several assays to monitor inhibition of Hsp90 function currently exist but are limited in their use for a drug discovery campaign. Using data from the crystal structure of an initial hit compound, we have developed a Xuorescence polarization assay to monitor binding of compounds to the ATP-binding site of Hsp90. This assay is very robust (Z' > 0.9) and can detect aYnity of compounds with IC50s to 40 nM. We have used this assay in conjunction with cocrystal structures of small molecules to drive a structure-based design program aimed at the discovery and optimization of a novel class of potent Hsp90 inhibitors.

U2 - 10.1016/j.ab.2005.12.023

DO - 10.1016/j.ab.2005.12.023

M3 - Article

VL - 350

SP - 202

EP - 213

JO - Analytical Biochemistry

JF - Analytical Biochemistry

SN - 0003-2697

IS - 2

ER -

ID: 142977