The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway

O. Giles Best; Nisha Singh; Cecily Forsyth; Stephen P. Mulligan

doi:10.1111/j.1365-2141.2010.08348.x

The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway

O. Giles Best, Nisha Singh, Cecily Forsyth, Stephen P. Mulligan

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

14 Citations (Scopus)

Abstract

Inhibitors of heat-shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP-70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL.

Original language	English
Pages (from-to)	185-188
Number of pages	4
Journal	British Journal of Haematology
Volume	151
Issue number	2
DOIs	https://doi.org/10.1111/j.1365-2141.2010.08348.x
Publication status	Published - Oct 2010
Externally published	Yes

Keywords

Antineoplastic Agents/*pharmacology Apoptosis/drug effects Benzamides/*pharmacology Benzoquinones/*pharmacology Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Genes, p53/genetics HSP90 Heat-Shock Proteins/*antagonists & inhibitors Hematologic Neoplasms/genetics/metabolism/pathology Humans Lactams, Macrocyclic/*pharmacology Leukemia, Lymphocytic, Chronic, B-Cell/genetics/metabolism/*pathology Mutation Neoplasm Proteins/metabolism Tumor Cells, Cultured ZAP-70 Protein-Tyrosine Kinase/metabolism

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title = "The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway",

abstract = "Inhibitors of heat-shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP-70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL.",

keywords = "Antineoplastic Agents/*pharmacology Apoptosis/drug effects Benzamides/*pharmacology Benzoquinones/*pharmacology Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Genes, p53/genetics HSP90 Heat-Shock Proteins/*antagonists & inhibitors Hematologic Neoplasms/genetics/metabolism/pathology Humans Lactams, Macrocyclic/*pharmacology Leukemia, Lymphocytic, Chronic, B-Cell/genetics/metabolism/*pathology Mutation Neoplasm Proteins/metabolism Tumor Cells, Cultured ZAP-70 Protein-Tyrosine Kinase/metabolism",

author = "Best, {O. Giles} and Nisha Singh and Cecily Forsyth and Mulligan, {Stephen P.}",

year = "2010",

month = oct,

doi = "10.1111/j.1365-2141.2010.08348.x",

language = "English",

volume = "151",

pages = "185--188",

journal = "British Journal of Haematology",

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number = "2",

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The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway. / Best, O. Giles; Singh, Nisha; Forsyth, Cecily; Mulligan, Stephen P.

In: British Journal of Haematology, Vol. 151, No. 2, 10.2010, p. 185-188.

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

TY - JOUR

T1 - The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway

AU - Best, O. Giles

AU - Singh, Nisha

AU - Forsyth, Cecily

AU - Mulligan, Stephen P.

PY - 2010/10

Y1 - 2010/10

N2 - Inhibitors of heat-shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP-70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL.

AB - Inhibitors of heat-shockprotein 90 (Hsp90) have been proposed as a novel therapeutic option for Chronic Lymphocytic Leukaemia (CLL), particularly as their mechanism of action appears independent of mutations of ATM or TP53. We investigated the activity of a novel Hsp90 inhibitor, SNX7081, against a panel of eight haematological cell lines and 23 CLL patient samples. SNX7081 displayed significant effects on cell cycle distribution, apoptotic rate and levels of ZAP-70 in the cell lines and in the patient samples, irrespective of TP53 status. Our findings suggest SNX7081 may represent a promising therapeutic option for aggressive CLL.

KW - Antineoplastic Agents/pharmacology Apoptosis/drug effects Benzamides/pharmacology Benzoquinones/pharmacology Dose-Response Relationship, Drug Drug Screening Assays, Antitumor Genes, p53/genetics HSP90 Heat-Shock Proteins/antagonists & inhibitors Hematolog

U2 - 10.1111/j.1365-2141.2010.08348.x

DO - 10.1111/j.1365-2141.2010.08348.x

M3 - Article

VL - 151

SP - 185

EP - 188

JO - British Journal of Haematology

JF - British Journal of Haematology

SN - 0007-1048

IS - 2

ER -

The novel Hsp-90 inhibitor SNX7081 is significantly more potent than 17-AAG against primary CLL cells and a range of haematological cell lines, irrespective of lesions in the TP53 pathway

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Keywords

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