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.
- 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