Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures

B  Dymock; X  Barril; M  Beswick; A  Collier; N  Davies; M  Drysdale; A  Fink; C  Fromont; R E  Hubbard; A  Massey; A  Surgenor; L  Wright

doi:10.1016/j.bmcl.2003.11.011

Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures

B Dymock, X Barril, M Beswick, A Collier, N Davies, M Drysdale, A Fink, C Fromont, R E Hubbard, A Massey, A Surgenor, L Wright

Chemistry

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

Abstract

Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	325-328
Number of pages	4
Journal	Bioorganic & Medicinal Chemistry Letters
Volume	14
Issue number	2
DOIs	https://doi.org/10.1016/j.bmcl.2003.11.011
Publication status	Published - 19 Jan 2004

Keywords

HSP90
chaperone
adenine inhibitors
HSP70
Raf-1
TISSUE DISTRIBUTION
CANCER-CELLS
PHARMACOKINETICS
DEGRADATION
DERIVATIVES
RADICICOL

Access to Document

10.1016/j.bmcl.2003.11.011

Cite this

Dymock, B., Barril, X., Beswick, M., Collier, A., Davies, N., Drysdale, M., Fink, A., Fromont, C., Hubbard, R. E., Massey, A., Surgenor, A., & Wright, L. (2004). Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures. Bioorganic & Medicinal Chemistry Letters, 14(2), 325-328. https://doi.org/10.1016/j.bmcl.2003.11.011

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title = "Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures",

abstract = "Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.",

keywords = "HSP90, chaperone, adenine inhibitors, HSP70, Raf-1, TISSUE DISTRIBUTION, CANCER-CELLS, PHARMACOKINETICS, DEGRADATION, DERIVATIVES, RADICICOL",

author = "B Dymock and X Barril and M Beswick and A Collier and N Davies and M Drysdale and A Fink and C Fromont and Hubbard, {R E} and A Massey and A Surgenor and L Wright",

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language = "English",

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Dymock, B, Barril, X, Beswick, M, Collier, A, Davies, N, Drysdale, M, Fink, A, Fromont, C, Hubbard, RE, Massey, A, Surgenor, A & Wright, L 2004, 'Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures', Bioorganic & Medicinal Chemistry Letters, vol. 14, no. 2, pp. 325-328. https://doi.org/10.1016/j.bmcl.2003.11.011

TY - JOUR

T1 - Adenine derived inhibitors of the molecular chaperone HSP90 - SAR explained through multiple X-ray structures

AU - Dymock, B

AU - Barril, X

AU - Beswick, M

AU - Collier, A

AU - Davies, N

AU - Drysdale, M

AU - Fink, A

AU - Fromont, C

AU - Hubbard, R E

AU - Massey, A

AU - Surgenor, A

AU - Wright, L

PY - 2004/1/19

Y1 - 2004/1/19

N2 - Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

AB - Multiple co-crystal structures of an adenine-based series of inhibitors bound to the molecular chaperone Hsp90 have been determined. These structures explain the observed SAR for previously described compounds and new compounds, which possess up to 8-fold improved potency against the isolated enzyme. Anti-tumour cell potency and mechanism of action data is also described for the most potent compounds. These data should enable the design of more potent Hsp90 inhibitors. (C) 2003 Elsevier Ltd. All rights reserved.

KW - HSP90

KW - chaperone

KW - adenine inhibitors

KW - HSP70

KW - Raf-1

KW - TISSUE DISTRIBUTION

KW - CANCER-CELLS

KW - PHARMACOKINETICS

KW - DEGRADATION

KW - DERIVATIVES

KW - RADICICOL

U2 - 10.1016/j.bmcl.2003.11.011

DO - 10.1016/j.bmcl.2003.11.011

M3 - Article

SN - 0960-894X

VL - 14

SP - 325

EP - 328

JO - Bioorganic & Medicinal Chemistry Letters

JF - Bioorganic & Medicinal Chemistry Letters

IS - 2

ER -