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 journalArticlepeer-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 languageEnglish
Pages (from-to)185-188
Number of pages4
JournalBritish Journal of Haematology
Volume151
Issue number2
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

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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